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  • 51.
    Mellergård, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Blystad, Ida
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Grönqvist, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Blennow,, K.
    Clinical Neurochemistry Laboratory, Institution of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Olsson,, B.
    Clinical Neurochemistry Laboratory, Institution of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab-treated multiple sclerosis2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, no 1, p. 112-121Article in journal (Refereed)
    Abstract [en]

    Background and purpose

    Brain atrophy is related to clinical deterioration in multiple sclerosis (MS) but its association with intrathecal markers of inflammation or neurodegeneration is unclear. Our aim was to investigate whether cerebrospinal fluid (CSF) markers of inflammation or neurodegeneration are associated with brain volume change in natalizumab-treated MS and whether this change is reflected in non-lesional white matter metabolites.

    Methods

    About 25 patients with natalizumab-treated MS were followed for 3 years with assessment of percentage brain volume change (PBVC) and absolute quantification of metabolites with proton magnetic resonance spectroscopy (1H MRS). Analyses of inflammatory [interleukin 1β (IL-1β), IL-6, C-X-C motif chemokine 8 (CXCL8), CXCL10, CXCL11, C-C motif chemokine 22] and neurodegenerative [neurofilament light protein (NFL), glial fibrillary acidic protein, myelin basic protein, tau proteins] markers were done at baseline and 1-year follow-up.

    Results

    The mean decline in PBVC was 3% at the 3-year follow-up, although mean 1H MRS metabolite levels in non-lesional white matter were unchanged. CSF levels of NFL and tau at baseline correlated negatively with PBVC over 3 years (r = −0.564, P = 0.012, and r = −0.592, P = 0.010, respectively).

    Conclusions

    A significant 3-year whole-brain atrophy was not reflected in mean metabolite change of non-lesional white matter. In addition, our results suggest that CSF levels of NFL and tau correlate with brain atrophy development and may be used for evaluating treatment response in inflammatory active MS.

  • 52.
    Mesic, Nedzad
    et al.
    Linköping University, Department of Social and Welfare Studies, Learning, Aesthetics, Natural science. Linköping University, Faculty of Educational Sciences.
    Dahlstedt, Magnus
    Linköping University, Department of Social and Welfare Studies, Social Work. Linköping University, Faculty of Arts and Sciences.
    Fejes, Andreas
    Linköping University, Department of Behavioural Sciences and Learning, Education and Adult Learning. Linköping University, Faculty of Educational Sciences.
    Nyström, Sofia
    Linköping University, Department of Behavioural Sciences and Learning, Education and Adult Learning. Linköping University, Faculty of Educational Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Use-Values for Inclusion: Mobilizing Resources in Popular Education for Newly Arrived Refugees in Sweden2019In: Social Inclusion, ISSN 2183-2803, E-ISSN 2183-2803, Vol. 7, no 2, p. 85-95Article in journal (Refereed)
    Abstract [en]

    In times of market reforms and international migration, the Swedish welfare model has been seriously challenged. In the context of the arrival of refugees in 2015-2017, the state turned to civil society in facing up to the challenges. In this article, we direct our attention to the Workers Educational Associations (ABF) state-funded work with refugees, with a specific focus on the activities conducted, the resources making them possible and the use-value of the resources mobilised. The article is based on observations and interviews with study circle leaders, managers and asylum seekers. The analysis illustrates that ABF, in line with its historical legacy, the broader workers movement, the strong notion of popular education as free and voluntary, has, with its well-established connections throughout the country, not solely taken on the task defined by the state. In solidarity, ABF has also responded to the needs of the refugees. As highlighted in the analysis, ABF has mobilized a wide range of resources, not least providing refugees with social networks and help in contacting the authorities. With such mobilization, opportunities were provided for the inclusion of refugees in Sweden.

  • 53.
    Mörtzell Henriksson, M.
    et al.
    Nephrol, Umeå, Sweden.
    Newman, E.
    Bone Marrow Transplant and Apheresis, New South Wales, Australia.
    Witt, V.
    St. Anna, Vienna, Austria.
    Derfler, K.
    AKH, Vienna, Austria.
    Leitner, G.
    AKH, Vienna, Austria.
    Eloot, S.
    Gent, Belgium.
    Dhondt, A.
    Gent, Belgium.
    Deeren, D.
    Roeselar, Belgium.
    Rock, G.
    Canada.
    Ptak, J.
    Frydek-Mistek, Czech Republic.
    Blaha, M.
    Hradec Kralove, Czech Republic.
    Lanska, M.
    Hradec Kralove, Czech Republic.
    Gasova, Z.
    Prague, Czech Republic.
    Hrdlickova, R.
    Ostrava, Czech Republic.
    Ramlow, W.
    Rostock, Germany.
    Prophet, H.
    Rostock, Germany.
    Liumbruno, G.
    Livorno, Italy.
    Mori, E.
    Livorno, Italy.
    Griskevicius, A.
    Vilnius, Lithuania.
    Audzijoniene, J.
    Vilnius, Lithuania.
    Vrielink, H.
    Amsterdam, The Netherlands.
    Rombout, S.
    Maastricht, The Netherlands.
    Aandahl, A.
    Oslo, Norway.
    Sikole, A.
    Skopje, Macedonia.
    Tomaz, J.
    Coimbra, Portugal.
    Lalic, K.
    Belgrade, Serbia.
    Mazic, S.
    Zagreb, Croatia.
    Strineholm, V.
    Orebro, Sweden.
    Brink, B.
    Huddinge, Sweden.
    Berlin, Gösta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Dykes, J.
    Lund, Sweden.
    Toss, F.
    BC, Umeå, Sweden.
    Axelsson, C.G.
    BC, Umeå, Sweden.
    Stegmayr, B.
    Nephrol, Umeå, Sweden.
    Nilsson, T.
    Nephrol, Uppsala, Sweden.
    Norda, R.
    BC, Uppsala, Sweden.
    Knutson, F.
    BC, Uppsala, Sweden.
    Ramsauer, B.
    Nephrol., Skövde, Sweden.
    Wahlström,, A.
    Nephrol., Karlstad, Sweden.
    Adverse events in apheresis: An update of the WAA registry data2016In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 54, no 1, p. 14p. 2-15Article, review/survey (Refereed)
    Abstract [en]

    Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.

  • 54.
    Nyström, Sofia
    Linköping University, Department of Behavioural Sciences and Learning, Education and Adult Learning. Linköping University, Faculty of Educational Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Yrkeslärande och handledning i arbete2019In: Lära till yrkeslärare / [ed] Susanne Köpsén, Lund: Studentlitteratur AB, 2019, 2 uppl., p. 193-216Chapter in book (Other academic)
  • 55.
    Nyström, Sofia
    Linköping University, Department of Behavioural Sciences and Learning, Education and Adult Learning. Linköping University, Faculty of Educational Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Yrkeslärande och handledning i arbete2019In: Lära till yrkeslärare / [ed] Susanne Köpsén, Lund: Studentlitteratur AB, 2019, 2, Vol. Sidorna 193-216, p. 193-216Chapter in book (Other academic)
  • 56.
    Oji, Satoru
    et al.
    Medical University of Vienna, Austria.
    Nicolussi, Eva-Maria
    Medical University of Vienna, Austria.
    Kaufmann, Nathalie
    Medical University of Vienna, Austria.
    Zeka, Bleranda
    Medical University of Vienna, Austria.
    Schanda, Kathrin
    Medical University of Innsbruck, Austria.
    Fujihara, Kazuo
    Tohoku University, Japan; Tohoku University, Japan.
    Illes, Zsolt
    University of Southern Denmark, Denmark.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Reindl, Markus
    Medical University of Innsbruck, Austria.
    Lassmann, Hans
    Medical University of Vienna, Austria.
    Bradl, Monika
    Medical University of Vienna, Austria.
    Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, p. e0151244-Article in journal (Refereed)
    Abstract [en]

    Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN.

  • 57.
    Ramström, Sofia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Södergren, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Tynngård, Nahreen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Platelet Function Determined by Flow Cytometry: New Perspectives?2016In: Seminars in Thrombosis and Hemostasis, ISSN 0094-6176, E-ISSN 1098-9064, Vol. 42, no 3, p. 268-281Article in journal (Refereed)
    Abstract [en]

    Flow cytometry enables studies of several different aspects of platelet function in response to a variety of platelet agonists. This can be done using only a small volume of whole blood, and also in blood with low platelet counts. These properties, together with the increasing number of flow cytometers available in hospitals worldwide, make flow cytometry an interesting option for laboratories interested in studies of platelet function in different clinical settings. This review focuses on practical issues regarding the use of flow cytometry for platelet function testing. It provides an overview of available activation markers, platelet agonists, and experimental setup issues. The review summarizes previous experience and factors important to consider to perform high-quality platelet function testing by flow cytometry. It also discusses its current use and possibilities and challenges for future use of flow cytometry in clinical settings

  • 58.
    Roepke, E. Rasmark
    et al.
    Malmo and Lund Univ, Sweden.
    Bruno, Valentina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Tor Vergata Univ Hosp, Italy; Tor Vergata Univ Hosp, Italy.
    Nedstrand, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Boij, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Strid, C. Petersson
    Kalmar Hosp, Sweden.
    Piccione, E.
    Tor Vergata Univ Hosp, Italy.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Svensson Arvelund, Judit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rubér, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Low-molecular-weight-heparin increases Th1-and Th17-associated chemokine levels during pregnancy in women with unexplained recurrent pregnancy loss: a randomised controlled trial2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12314Article in journal (Refereed)
    Abstract [en]

    Low-molecular-weight heparin (LMWH) is widely used to treat recurrent pregnancy loss (RPL) because of its anti-coagulant effects. Although in vitro studies have suggested additional immunological effects, these are debated. We therefore investigated whether LMWH could modulate immune responses in vivo during pregnancy of women with unexplained RPL. A Swedish open multi-centre randomised controlled trial included 45 women treated with tinzaparin and 42 untreated women. Longitudinally collected plasma samples were obtained at gestational weeks (gw) 6, 18, 28 and 34 and analysed by multiplex bead technology for levels of 11 cytokines and chemokines, chosen to represent inflammation and T-helper subset-associated immunity. Mixed linear models test on LMWH-treated and untreated women showed differences during pregnancy of the Th1-associated chemokines CXCL10 (p = 0.01), CXCL11 (p amp;lt; 0.001) and the Th17-associated chemokine CCL20 (p = 0.04), while CCL2, CCL17, CCL22, CXCL1, CXCL8, CXCL12, CXCL13 and IL-6 did not differ. Subsequent Students t-test showed significantly higher plasma levels of CXCL10 and CXCL11 in treated than untreated women at gw 28 and 34. The consistent increase in the two Th1-associated chemokines suggests a potential proinflammatory and unfavourable effect of LMWH treatment during later stages of pregnancy, when Th1 immunity is known to disrupt immunological tolerance.

  • 59.
    Sandgren, Per
    et al.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Berlin, Gösta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Tynngård, Nahreen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Treatment of platelet concentrates with ultraviolet C light for pathogen reduction increases cytokine accumulation2016In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 56, no 6, p. 1377-1383Article in journal (Refereed)
    Abstract [en]

    BACKGROUNDPathogen reduction technologies use photoactive substances in combination with ultraviolet (UV) light to inactivate pathogens. A new method uses only UVC light for pathogen reduction. This study assesses the effects of UVC light treatment on cytokine release in platelet (PLT) concentrates (PCs). STUDY DESIGN AND METHODSA PC with 35% plasma and 65% PLT additive solution (SSP+) was prepared from five buffy coats. Three such PCs were pooled and divided into 3 units. One unit was used as a nonirradiated control, the second was a gamma-irradiated control, and the third unit was treated with UVC light technology. Ten units of each type were investigated. Cytokine release was analyzed on Days 1, 5, and 7 of storage. Correlation between cytokines, PLT surface markers, and hemostatic properties was investigated. RESULTSSwirling was well preserved and pH was above the reference limit of 6.4 during storage of PLTs in all groups. Cytokine levels increased during storage in all groups but to a larger degree in PCs treated with UVC light. Only weak correlation was found between cytokines and PLT surface markers (ramp;lt;0.5). However, several cytokines showed strong correlation (ramp;gt;0.6) with the PLTs ability to promote clot retraction. CONCLUSIONUVC treatment resulted in increased release from PLT alpha granules as evident by a higher cytokine release compared to nonirradiated and gamma-irradiated PCs. The clinical relevance of these findings needs to be further evaluated.

  • 60.
    Sharma, Surendra
    et al.
    Department of Pediatrics, Women and Infants Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Obituary: Leif Matthiesen, MD, PhD (1954‐2017)2017In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 78, no 4, article id e12740Article in journal (Other academic)
    Abstract [en]

    Leif Matthiesen, an evergreen member and supporter of the American Society for Reproductive Immunology (ASRI), died on April 29, 2017, following a hard fought battle with glioblastoma. We all hoped that Leif being a fearless person and a fun‐loving physician scientist would beat all the odds against this dreaded disease and come out of it with flying colors. Alas, our hopes were given a serious thought by the Almighty. We as a community of friends and scientific colleagues are saddened by the loss of such a wonderful human being and a noteworthy member of the ASRI.

  • 61.
    Stegmayr, B.
    et al.
    Umeå University, Sweden.
    Mortzell Henriksson, M.
    Umeå University, Sweden.
    Newman, E.
    Bone Marrow Transplant & Apheresis, New South Wales, Australia.
    Witt, V.
    St Anna, Austria.
    Derfler, K.
    AKH, Austria.
    Leitner, G.
    AKH, Austria.
    Eloot, S.
    University Hospital, Belgium.
    Dhondt, A.
    University Hospital, Belgium.
    Deeren, D.
    AZ Delta, Belgium.
    Rock, G.
    Canadian Apheresis Grp, Canada.
    Ptak, J.
    Transfusion Medicine, Frydek-Mistek, Czechia.
    Blaha, M.
    Transfusion Medicine, Hradec Kralove, Czechia.
    Lanska, M.
    Transfusion Medicine, Hradec Kralove, Czechia.
    Gasova, Z.
    Institute Hematol and Blood Transfus, Czech Republic.
    Bhuiyan-Ludvikova, Z.
    Institute Hematol and Blood Transfus, Czech Republic.
    Hrdlickova, R.
    University Hospital, Czech Republic.
    Ramlow, W.
    Apheresis Centre North, Germany.
    Prophet, H.
    Apheresis Centre North, Germany.
    Liumbruno, G.
    National Institute Heatlh, Italy.
    Mori, E.
    Centre Blood, Italy.
    Griskevicius, A.
    University Hospital, Lithuania.
    Audzijoniene, J.
    University Hospital, Lithuania.
    Vrielink, H.
    Sanquin, Netherlands.
    Rombout-Sestrienkova, E.
    Sanquin, Netherlands.
    Aandahl, A.
    Akers University Hospital, Norway.
    Sikole, A.
    University Hospital, Macedonia.
    Tomaz, J.
    Coimbra University Hospital, Portugal.
    Lalic, K.
    University Hospital, Serbia.
    Bojanic, I.
    University of Zagreb, Croatia.
    Strineholm, V.
    University Hospital, Sweden.
    Brink, B.
    Huddinge University Hospital, Sweden.
    Berlin, Gösta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Dykes, J.
    University of Lund Hospital, Sweden.
    Toss, F.
    University Hospital, Sweden.
    Nilsson, T.
    University of Uppsala Hospital, Sweden.
    Knutson, F.
    Uppsala University, Sweden.
    Ramsauer, B.
    Skaraborg Hospital, Sweden.
    Wahlstrom, A.
    Department Nephrol, Sweden.
    Distribution of indications and procedures within the framework of centers participating in the WAA apheresis registry2017In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 56, no 1, p. 71-74Article in journal (Refereed)
    Abstract [en]

    The WAA apheresis registry was established in 2003 and an increasing number of centers have since then included their experience and data of their procedures. The registry now contains data of more than 74,000 apheresis procedures in more than 10,000 patients. This report shows that the indications for apheresis procedures are changing towards more ontological diagnoses and stem cell collections from patients and donors and less therapeutic apheresis procedures. In centers that continue to register, the total extent of apheresis procedures and patients treated have expanded during the latest years. (C) 2016 Elsevier Ltd. All rights reserved.

  • 62.
    Strindhall, Jan
    et al.
    Jonköping University, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Morner, Andreas
    Public Health Agency Sweden, Sweden.
    Waalen, Kristian
    Norwegian Institute Public Heatlh, Norway.
    Lofgren, Sture
    Ryhov County Hospital, Sweden.
    Matussek, Andreas
    Ryhov County Hospital, Sweden.
    Bengner, Malin
    Ryhov County Hospital, Sweden.
    Humoral response to influenza vaccination in relation to pre-vaccination antibody titres, vaccination history, cytomegalovirus serostatus and CD4/CD8 ratio2016In: INFECTIOUS DISEASES, ISSN 2374-4235, Vol. 48, no 6, p. 436-442Article in journal (Refereed)
    Abstract [en]

    Background Annual vaccination against influenza virus is generally recommended to elderly and chronically ill, but the relative importance of factors influencing the outcome is not fully understood. Methods In this study of 88 individuals all aged 69 years, the increase in haemagglutinin-inhibiting (HI) antibodies to trivalent inactivated influenza vaccine was correlated with HI titres before vaccination, prior vaccinations against influenza, cytomegalovirus serostatus and, as an estimate of immune risk profile, the ratio between CD4 + and CD8 + T cells. Results Vaccine responses were impaired by high pre-existing HI antibody titres. For influenza B repeated vaccinations and an inverse CD4/CD8 ratio had a negative impact on the vaccine response. Cytomegalovirus seropositivity had no apparent effect on HI titres before or after vaccination. Conclusions It is concluded that both pre-existing HI antibodies and previous vaccinations to influenza may influence the humoral response to influenza vaccination and that a CD4/CD8 ratio < 1 may indicate an impaired ability to respond to repeated antigenic stimulation.

  • 63.
    Strindhall, Jan
    et al.
    Jonköping University, Sweden.
    Löfgren, Sture
    Ryhov County Hospital, Sweden.
    Framsth, Caroline
    Ryhov County Hospital, Sweden.
    Matussek, Andreas
    Ryhov County Hospital, Sweden; Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Bengner, Malin
    Ryhov County Hospital, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Wikby, Anders
    Jönköping University, Sweden.
    CD4/CD8 ratio < 1 is associated with lymphocyte subsets, CMV and gender in 71-year old individuals: 5-Year follow-up of the Swedish HEXA Immune Longitudinal Study2017In: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 95, p. 82-87Article in journal (Refereed)
    Abstract [en]

    n/a

  • 64.
    Strollo, Rocky
    et al.
    Univ Campus Biomed Roma, Italy.
    Vinci, Chiara
    Univ Campus Biomed Roma, Italy; Queen Mary Univ London, England.
    Napoli, Nicola
    Univ Campus Biomed Roma, Italy; IRCCS Ist Ortoped Galeazzi, Italy.
    Fioriti, Elvira
    Univ Campus Biomed Roma, Italy.
    Maddaloni, Ernesto
    Univ Campus Biomed Roma, Italy.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Pozzilli, Paolo
    Univ Campus Biomed Roma, Italy; Queen Mary Univ London, England.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Nissim, Ahuva
    Queen Mary Univ London, England.
    Antibodies to oxidized insulin improve prediction of type 1 diabetes in children with positive standard islet autoantibodies2019In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, DIABETES-METABOLISM RESEARCH AND REVIEWS, Vol. 35, no 4, article id e3132Article in journal (Refereed)
    Abstract [en]

    Background

    Antibodies to posttranslationally modified insulin (oxPTM‐INS‐Ab) are a novel biomarker of type 1 diabetes (T1D). Here, we evaluated whether oxPTM‐INS‐Ab can improve T1D prediction in children with positive standard islet autoantibodies (AAB).

    Methods

    We evaluated sensitivity, specificity, accuracy, and risk for progression to T1D associated with oxPTM‐INS‐Ab and the standard islet AAB that include insulin (IAA), GAD (GADA), and tyrosine phosphatase 2 (IA‐2A) in a cohort of islet AAB‐positive (AAB+) children from the general population (median follow‐up 8.8 years).

    Results

    oxPTM‐INS‐Ab was the most sensitive and specific autoantibody biomarker (74% sensitivity, 91% specificity), followed by IA‐2A (71% sensitivity, 91% specificity). GADA and IAA showed lower sensitivity (65% and 50%, respectively) and specificity (66% and 68%, respectively). Accuracy (AUC of ROC) of oxPTM‐INS‐Ab was higher than GADA and IAA (P = 0.003 and P = 0.017, respectively), and similar to IA‐2A (P = 0.896). oxPTM‐INS‐Ab and IA‐2A were more effective than IAA for detecting progr‐T1D when used as second‐line biomarker in GADA+ children. Risk for diabetes was higher (P = 0.03) among multiple AAB+ who were also oxPTM‐INS‐Ab+ compared with those who were oxPTM‐INS‐Ab–. Importantly, when replacing IAA with oxPTM‐INS‐Ab, diabetes risk increased to 100% in children with oxPTM‐INS‐Ab+ in combination with GADA+ and IA‐2A+, compared with 84.37% in those with IAA+, GADA+, and IA‐2A+ (P = 0.04).

    Conclusions

    Antibodies to oxidized insulin (oxPTM‐INS‐Ab), compared with IAA which measure autoantibodies to native insulin, improve T1D risk assessment and prediction accuracy in AAB+ children.

  • 65.
    Svensson Arvelund, Judit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    The Role of Macrophages in Promoting and Maintaining Homeostasis at the Fetal-Maternal Interface2015In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 74, no 2, p. 100-109Article, review/survey (Refereed)
    Abstract [en]

    A successful pregnancy requires that the maternal immune system adapts properly to avoid rejection of the semi-allogeneic fetus without compromising the ability to protect the mother and the fetus against infections. In this review, we describe the role of decidual macrophages in creating a homeostatic environment at the fetal-maternal interface. We also discuss their role in pregnancy complications as well as future possibilities to modulate macrophage function therapeutically. Decidual macrophages are enriched at the fetal-maternal interface and play a major role in the regulation of inflammatory responses and the maintenance of a tolerant environment. Their function is, however, not restricted to immune tolerance, but extends to include functions such as the recognition and clearance of infections, the clearance of apoptotic debris, and tissue remodeling. Decidual macrophages seem to largely function as tissue-resident macrophages that are crucial for maintaining homeostasis and reproductive success.

  • 66.
    Svensson Arvelund, Judit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Söderberg, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Wendel, Caroline
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Freland, Sofia
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Geffers, Robert
    Mucosal Immunity, Helmholtz Centre for Infection Research (HCI), Braunschweig, Germany.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Decidual macrophages contribute to the unique leukocyte composition at the fetal-maternal interface by production of IL-35, induction of Treg cells and production of homeostatic chemokines2015Manuscript (preprint) (Other academic)
    Abstract [en]

    Reproductive success depends on the ability of the maternal immune system to adapt in order to tolerate and support the growing semi-allogenic fetus. Macrophages, being a major leukocyte population in the uterine mucosa (decidua), may play a central role in promoting the unique composition and regulatory phenotype of leukocytes that is characteristic for the fetal-maternal interface. We show that decidual macrophages display a predominantly immune regulatory gene profile and produce the immunosuppressive cytokine IL-35 but no other members of the IL-12 family (IL-12, IL-23 and IL-27). Decidual macrophages also promoted the selective expansion of CD25highFoxp3+ Tregs but not of Tbet+ Th1, GATA-3+ Th2 and Rorγt+ Th17 cells. In addition, these macrophages preferentially secreted the monocyte- and Treg-associated chemokines CCL2 and CCL18, while Th1-, Th2- and Th17-related chemokines were produced at low levels. Among in vitro macrophages, distinct chemokine profiles were observed; IL-4/13 upregulated Th2-associated chemokines (CCL17, CCL22, CCL26) while LPS/IFNγ upregulated Th1-associated chemokines (CXCL9, CXCL10, CXCL11, CCL5). M(IL-10) macrophages (induced by M-CSF and IL-10) showed a chemokine profile similar to that of decidual macrophages, as shown by gene expression and protein analysis. By using M(IL-10) macrophages as a model of decidual macrophages, we show that these cells promote the recruitment of CD14+ monocytes, while migration of several lymphocyte populations was unaltered or prevented. These data implicate decidual macrophages as critical regulators of the decidual leukocyte composition and phenotype that is associated with successful reproduction.

  • 67.
    Svensson, Judit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Bhai Mehta, Ratnesh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Lindau, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Mirrasekhian, Elahe
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Lash, Gendie E.
    Newcastle University, England.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    The Human Fetal Placenta Promotes Tolerance against the Semiallogeneic Fetus by Inducing Regulatory T Cells and Homeostatic M2 Macrophages2015In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 194, no 4, p. 1534-1544Article in journal (Refereed)
    Abstract [en]

    A successful pregnancy requires that the maternal immune system is instructed to a state of tolerance to avoid rejection of the semiallogeneic fetal-placental unit. Although increasing evidence supports that decidual (uterine) macrophages and regulatory T cells (Tregs) are key regulators of fetal tolerance, it is not known how these tolerogenic leukocytes are induced. In this article, we show that the human fetal placenta itself, mainly through trophoblast cells, is able to induce homeostatic M2 macrophages and Tregs. Placental-derived M-CSF and IL-10 induced macrophages that shared the CD14(+)CD163(+)CD206(+)CD209(+) phenotype of decidual macrophages and produced IL-10 and CCL18 but not IL-12 or IL-23. Placental tissue also induced the expansion of CD25(high)CD127(low)Foxp3(+) Tregs in parallel with increased IL-10 production, whereas production of IFN-gamma (Th1), IL-13 (Th2), and IL-17 (Th17) was not induced. Tregs expressed the suppressive markers CTLA-4 and CD39, were functionally suppressive, and were induced, in part, by IL-10, TGF-beta, and TRAIL. Placental-derived factors also limited excessive Th cell activation, as shown by decreased HLA-DR expression and reduced secretion of Th1-, Th2-, and Th17-associated cytokines. Thus, our data indicate that the fetal placenta has a central role in promoting the homeostatic environment necessary for successful pregnancy. These findings have implications for immune-mediated pregnancy complications, as well as for our general understanding of tissue-induced tolerance.

  • 68.
    Södergren, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Tynngård, Nahreen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Berlin, Gösta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Responsiveness of platelets during storage studied with flow cytometry - formation of platelet subpopulations and LAMP-1 as new markers for the platelet storage lesion2016In: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 110, no 2, p. 116-125Article in journal (Refereed)
    Abstract [en]

    Background and ObjectivesStorage lesions may prevent transfused platelets to respond to agonists and arrest bleeding. The aim of this study was to evaluate and quantify the capacity of platelet activation during storage using flow cytometry and new markers of platelet activation. Materials and MethodsActivation responses of platelets prepared by apheresis were measured on days 1, 5, 7 and 12. In addition, comparisons were made for platelet concentrates stored until swirling was affected. Lysosome-associated membrane protein-1 (LAMP-1), P-selectin and phosphatidylserine (PS) exposure were assessed by flow cytometry on platelets in different subpopulations in resting state or following stimulation with platelet agonists (cross-linked collagen-related peptide (CRP-XL), PAR1- and PAR4-activating peptides). ResultsThe ability to form subpopulations upon activation was significantly decreased already at day 5 for some agonist combinations. The agonist-induced exposure of PS and LAMP-1 also gradually decreased with time. Spontaneous exposure of P-selectin and PS increased with time, while spontaneous LAMP-1 exposure was unchanged. In addition, agonist-induced LAMP-1 expression clearly discriminated platelet concentrates with reduced swirling from those with retained swirling. This suggests that LAMP-1 could be a good marker to capture changes in activation capacity in stored platelets. ConclusionThe platelet activation potential seen as LAMP-1 exposure and fragmentation into platelet subpopulations is potential sensitive markers for the platelet storage lesion.

  • 69.
    Theodorsson, Elvar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Löwbeer, Christian
    Aleris Medilab och Institutionen för laboratoriemedicin, Avdelningen för klinisk kemi, Karolinska institutet, Stockholm.
    Ridefelt, Peter
    Institutionen för medicinska vetenskaper, Klinisk kemi, Uppsala universitet.
    Carlson, Marie
    Institutionen för sociologi och arbetsvetenskap, Göteborgs universitet.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Simonsson, Per
    Institutionen för translationell medicin, Medicinska fakulteten, Lunds universitet.
    Digestionsorganens sjukdomar2018In: Laurells klinisk kemi i praktisk medicin, Lund: Studentlitteratur AB, 2018, 10, p. 465-516Chapter in book (Other academic)
  • 70.
    Thomas, Owain
    et al.
    Lund University, Sweden; SUS Lund University Hospital, Sweden.
    Larsson, Anna
    Lund University, Sweden.
    Tynngård, Nahreen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Schott, Ulf
    Lund University, Sweden; SUS Lund University Hospital, Sweden.
    Thromboelastometry versus free-oscillation rheometry and enoxaparin versus tinzaparin: an in-vitro study comparing two viscoelastic haemostatic tests dose-responses to two low molecular weight heparins at the time of withdrawing epidural catheters from ten patients after major surgery2015In: BMC Anesthesiology, ISSN 1471-2253, E-ISSN 1471-2253, Vol. 15Article in journal (Refereed)
    Abstract [en]

    Background: Monitoring low molecular weight heparins (LMWHs) in the perioperative period is prudent in patients at high risk of coagulative complications, especially when the patient has an epidural catheter requiring withdrawal, which is associated with the risk of spinal haematoma. The aim of this study was to evaluate the in vitro dose-responses of two different LMWHs on two different viscoelastic haemostatic tests, using blood sampled from patients with normal routine coagulation parameters, on the day after major surgery when their epidural catheters were due to be withdrawn. Methods: Enoxaparin or tinzaparin were added in vitro to blood from ten patients who had undergone oesophageal resection, to obtain plasma concentrations of approximately 0, 0.5, 1.0 and 1.5 IU/mL. Coagulation was monitored using thromboelastometry (ROTEM (R)) using the InTEM (R) activating reagent; and free oscillation rheometry (FOR: ReoRox (R)), activated using thromboplastin. Clot initiation was measured using ROTEM-CT, ReoRox-COT1 and ReoRox-COT2. Clot propagation was measured using ROTEM-CFT, ROTEM-Alpha Angle and ReoRox-Slope. Clot stability was measured using ROTEM-MCF and ReoRox-Gmax, and clot lysis was measured using ROTEM-ML and ReoRox-ClotSR. Results: Clot initiation time assessed by thromboelastometry and FOR was prolonged by increasing concentrations of both LMWHs (P &lt; 0.01). Equivalent doses of tinzaparin in international units (anti FXa units) per millilitre prolonged clot initiation more than enoxaparin (P &lt; 0.05). There was significant inter-individual variation - the ranges of CT and COT1 at LMWH-concentrations of 0 and 1.5 IU/mL overlapped. None of the tests reflecting clot formation rate or stability showed a dose-response to either LMWH but clot lysis showed a tentative negative dose-response to the LMWHs. Conclusions: Clot initiation times dose-dependent prolongation by LMWHs in this study agrees with previous research, as does tinzaparins stronger anti-coagulative effect than enoxaparin at equivalent levels of anti-FXa activity. This casts doubt on the validity of using anti-FXa assays alone to guide dosage of LMWHs. The significant inter-individual variation in dose-response suggests that the relationship between dose and effect in the postoperative period is complicated. While both ROTEM and FOR may have some role in postoperative monitoring, more research is needed before any conclusion can be made about their clinical usefulness.

  • 71.
    Thomas, Owain
    et al.
    Lund University, Sweden; SUS Lund University Hospital, Sweden.
    Lybeck, Emanuel
    Lund University, Sweden.
    Strandberg, Karin
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Tynngård, Nahreen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Schott, Ulf
    Lund University, Sweden; SUS Lund University Hospital, Sweden.
    Monitoring Low Molecular Weight Heparins at Therapeutic Levels: Dose-Responses of, and Correlations and Differences between aPTT, Anti-Factor Xa and Thrombin Generation Assays2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 1, article id e0116835Article in journal (Refereed)
    Abstract [en]

    Background Low molecular weight heparins (LMWHs) are used to prevent and treat thrombosis. Tests for monitoring LMWHs include anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT) and thrombin generation. Anti-FXa is the current gold standard despite LMWHs varying affinities for FXa and thrombin. Aim To examine the effects of two different LMWHs on the results of 4 different aPTT-tests, anti-FXa activity and thrombin generation and to assess the tests concordance. Method Enoxaparin and tinzaparin were added ex-vivo in concentrations of 0.0, 0.5, 1.0 and 1.5 anti-FXa international units (IU)/mL, to blood from 10 volunteers. aPTT was measured using two whole blood methods (Free oscillation rheometry (FOR) and Hemochron Jr (HCJ)) and an optical plasma method using two different reagents (ActinFSL and PTT-Automat). Anti-FXa activity was quantified using a chromogenic assay. Thrombin generation (Endogenous Thrombin Potential, ETP) was measured on a Ceveron Alpha instrument using the TGA RB and more tissue-factor rich TGA RC reagents. Results Methods mean aPTT at 1.0 IU/mL LMWH varied between 54s (SD 11) and 69s (SD 14) for enoxaparin and between 101s (SD 21) and 140s (SD 28) for tinzaparin. ActinFSL gave significantly shorter aPTT results. aPTT and anti-FXa generally correlated well. ETP as measured with the TGA RC reagent but not the TGA RB reagent showed an inverse exponential relationship to the concentration of LMWH. The HCJ-aPTT results had the weakest correlation to anti-FXa and thrombin generation (R(s)0.62-0.87), whereas the other aPTT methods had similar correlation coefficients (R(s)0.80-0.92). Conclusions aPTT displays a linear dose-respone to LMWH. There is variation between aPTT assays. Tinzaparin increases aPTT and decreases thrombin generation more than enoxaparin at any given level of anti-FXa activity, casting doubt on anti-FXas present gold standard status. Thrombin generation with tissue factor-rich activator is a promising method for monitoring LMWHs.

  • 72.
    Tingström, Pia
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Milberg, Anna
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Advanced Home Care in Norrköping. Region Östergötland, Local Health Care Services in East Östergötland, Center of Palliative Care.
    Rodhe, N.
    Uppsala University, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Grodzinsky, Ewa
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Sund-Levander, Märtha
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Nursing assistants: "He seems to be ill" - a reason for nurses to take action: validation of the Early Detection Scale of Infection (EDIS)2015In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 15, no 122Article in journal (Refereed)
    Abstract [en]

    Background: Signs and symptoms of infection in frail elderly are atypical, causing delay in diagnosis and treatment. To improve communication between healthcare staff of signs and symptoms of infection we developed an instrument, using qualitative data from observations by nursing assistants when they suspected infection. The aim of this study was to assess the validity of nursing assistants observations by developing and testing the instrument for early detection of infection in elderly nursing home residents. Methods: The early detection of infection (EDIS) instrument was based on data from focus interviews with nursing assistants. Over one year the nursing assistants used EDIS to document episodes of suspected early signs and symptoms of infection in 204 nursing home residents. Two physicians classified documented episodes as "no infection", "possible infection", and "infection". The content validity of the 13 items of the EDIS was established to explore the relationships between the items. The construct validity was used to explore the relationship between the items and the presence or absence of infection. The predictive value of the developed model was evaluated by the percentage of correct classifications of the observed cases. Generalized linear model (ordinal multinomial distribution and logit link) was used. Results: Of the 388 events of suspected infection, 20 % were assessed as no infection, 31 % as possible infection and 49 % as infection. Content validity analysis showed that 12/13 of the items correlated significantly with at least one other statement. The range in number of significant inter-correlations was from 0 ("pain") to 8 ("general signs and symptoms of illness"). The construct validity showed that the items "temperature", "respiratory symptoms" and "general signs and symptoms of illness" were significantly related to "infection", and these were also selected in the model-building. These items predicted correct alternative responses in 61 % of the cases. Conclusion: The validation of EDIS suggests that the observation of "general signs and symptoms of illness", made by nursing assistants should be taken seriously in detecting early infection in frail elderly. Also, the statement "He/She is not as usual" should lead to follow-up.

  • 73.
    Tjernberg, Anna Rockert
    et al.
    Kalmar Cty Hosp, Sweden; Orebro Univ, Sweden.
    Woksepp, Hanna
    Kalmar Cty Hosp, Sweden.
    Sandholm, Kerstin
    Linnaeus Univ, Sweden.
    Johansson, Marcus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Ludvigsson, Jonas F.
    Karolinska Inst, Sweden; Orebro Univ Hosp, Sweden.
    Bonnedahl, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Per
    Linnaeus Univ, Sweden; Univ Oslo, Norway.
    Ekdahl, Kristina Nilsson
    Linnaeus Univ, Sweden; Uppsala Univ, Sweden.
    Celiac disease and complement activation in response to Streptococcus pneumoniae2019In: European Journal of Pediatrics, ISSN 0340-6199, E-ISSN 1432-1076Article in journal (Refereed)
    Abstract [en]

    Individuals with celiac disease (CD) are at increased risk of invasive pneumococcal disease (IPD). The aim of this study was to explore whether the complement response to Streptococcus pneumoniae differed according to CD status, and could serve as an explanation for the excess risk of IPD in CD. Twenty-two children with CD and 18 controls, born 1999-2008, were included at Kalmar County Hospital, Sweden. The degree of complement activation was evaluated by comparing levels of activation products C3a and sC5b-9 in plasma incubated for 30 min with Streptococcus pneumoniae and in non-incubated plasma. Complement analyses were performed with enzyme-linked immunosorbent assay (ELISA). Pneumococcal stimulation caused a statistically significant increase in C3a as well as sC5b-9 in both children with CD and controls but there was no difference in response between the groups. After incubation, C3a increased on average 4.6 times and sC5b-9 22 times in both the CD and the control group (p = 0.497 and p = 0.724 respectively). Conclusion: Complement response to Streptococcus pneumoniae seems to be similar in children with and without CD and is thus unlikely to contribute to the increased susceptibility to invasive pneumococcal disease in CD.

  • 74.
    Toss, Fredrik
    et al.
    Umea Univ, Sweden.
    Edgren, Gustaf
    Karolinska Inst, Sweden; Soder Sjukhuset, Sweden.
    Berlin, Gösta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Stegmayr, Bernd
    Umea Univ, Sweden.
    Witt, Volker
    UKKJ Med Univ Vienna, Austria.
    Does prophylactic calcium in apheresis cause more harm than good? - Centre heterogeneity within the World Apheresis Association Register prevents firm conclusions2018In: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 113, no 7, p. 632-638Article in journal (Refereed)
    Abstract [en]

    Background and objectivesMaterials and methodsSymptomatic hypocalcaemia is common during apheresis procedures based on citrate-based anticoagulants. As a consequence, patients often receive prophylactic calcium treatment. However, a recent publication based on the World Apheresis Association (WAA) register suggested harmful effects of such prophylactic calcium use. Recognizing possible limitations in the previous WAA register analyses, we critically re-evaluate the data, to test whether a change in prophylactic calcium usage may be warranted. Using the WAA register, we reanalysed previous data by means of centre and treatment type stratification, to explore the role of prophylactic calcium as a risk factor for adverse events. ResultsConclusionThere was large variability in adverse event rates dependent on the centre performing the apheresis procedure and dependent on the type of procedure. When this variability was accounted for, there was no clear effect of calcium administration on risk of adverse effects. Shortcomings in the previous WAA register analyses may have failed to account for important confounding factors resulting in a substantial overestimation of the risk attributable to calcium usage. Overall our findings do not support a negative effect of prophylactic calcium administration in the apheresis setting.

  • 75.
    Tynngård, Nahreen
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regional Board, Research and Development Unit.
    Boknäs, Niklas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Trinks, Marie
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Dreimane, Arta
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Berlin, Gösta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Storage-induced change in platelet transfusion response evaluated by serial transfusions from one donor to one patient2019In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 59, no 2, p. 723-728Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Storage of platelet concentrates (PCs) results in storage lesions with possible detrimental effects on platelet recovery after transfusion, which might affect their ability to prevent or arrest bleeding. The aim of this study was to compare the quality of PCs stored for 1 to 3 or 5 to 7 days by assessing the corrected count increment (CCI) after transfusion. To isolate the effects of storage time, we studied serial transfusions of PCs obtained from one donor and one donation, and transfused to one single recipient after storage for 1 to 3 days and 5 to 7 days.

    STUDY DESIGN AND METHODS

    Platelets were obtained from one donor by apheresis, divided into two units (>240 × 109platelets/unit) and stored for 1 to 3 and 5 to 7 days, respectively, before transfusion. The PCs were transfused on normal indications to patients undergoing treatment at the hematology ward. Platelet count was measured before and after transfusion.

    RESULTS

    Thirty patients concluded the study according to the protocol. The mean storage time was 2.4 ± 0.7 and 5.7 ± 0.8 days for platelets transfused on Days 1 to 3 and 5 to 7, respectively. Storage for 5 to 7 days decreased the 1‐hour transfusion response as compared to platelets stored 1 to 3 days, from a CCI of 17 ± 7 to 13 ± 5. Despite this decrease, 86% of the 5 to 7 days stored PCs resulted in a CCI above the cutoff value for a successful transfusion of 7.5, which was not significantly different to PCs stored for 1 to 3 days.

    CONCLUSION

    Storage of PCs for 5 to 7 days only slightly altered the transfusion response.

  • 76.
    Tynngård, Nahreen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Trinks, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Berlin, Gösta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    In vitro function of platelets treated with ultraviolet C light for pathogen inactivation: a comparative study with nonirradiated and gamma-irradiated platelets2015In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 55, no 6, p. 1169-1177Article in journal (Refereed)
    Abstract [en]

    BackgroundDuring storage of platelet concentrates (PCs) replication of contaminating pathogens might occur, which can be prevented by various pathogen inactivation (PI) methods using photoactive substances in combination with ultraviolet (UV) light. A new method uses only UVC light for PI without photoactive substances. This study evaluates the in vitro function, including hemostatic properties (clot formation and elasticity), of platelets (PLTs) treated with UVC light. Study Design and MethodsA PC with 35% plasma and 65% PLT additive solution (SSP+) was prepared from five buffy coats. Three PCs were pooled and divided into 3units. One unit was used as a nonirradiated control, the second was a gamma-irradiated control, and the third unit was treated with UVC light. In vitro variables including analysis of coagulation by free oscillation rheometry were analyzed on Days 1, 5, and 7 of storage. Ten units in each group were investigated. ResultsSwirling was well preserved, and the pH level was higher than the reference limit (6.4) during storage of PLTs in all groups. Glycolysis and PLT activation were higher for UVC-treated PLTs but the clot-forming capacity was unaffected. However, immediately after UVC treatment, the clot elastic properties were slightly affected. Hypotonic shock response decreased immediately after UVC treatment but recovered partly during the storage period. ConclusionUVC treatment affected the in vitro properties, but PLT quality and storage stability were well preserved for up to 7 days, and the in vitro hemostatic capacity of UVC-treated PLTs was only minimally altered. The clinical relevance of these changes needs to be evaluated in controlled trials.

  • 77.
    Tynngård, Nahreen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Wallstedt, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Södergren, Anna L
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Faxälv, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Platelet adhesion changes during storage studied with a novel method using flow cytometry and protein-coated beads2015In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 26, no 2, p. 177-185Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to set up and evaluate a novel method for studies of platelet adhesion and activation in blood and platelet suspensions such as platelet concentrate (PC) samples using protein-coated polystyrene beads and flow cytometry. To demonstrate its usefulness, we studied PCs during storage. PCs were prepared by aphaeresis technique (n = 7). Metabolic variables and platelet function was measured on day 1, 5, 7 and 12 of storage. Spontaneous and TRAP-6-induced adhesion to fibrinogen- and collagen-coated beads was analyzed by flow cytometry. P-selectin and phosphatidyl serine (PS) expression was assessed on platelets bound to beads as well as on non-adherent platelets. Platelet adhesion to fibrinogen beads had increased by day 12 and adhesion to collagen beads at day 7 of storage (p < 0.05). TRAP-6 stimulation significantly increased the platelet adhesion to fibrinogen beads (p < 0.05) as well as the P-selectin and PS exposure on platelets bound to beads (p < 0.01) during the first 7 days of storage, but by day 12, significant changes were no longer induced by TRAP-6 stimulation. We demonstrate that our adhesion assay using protein-coated polystyrene beads can be used to assess the adhesion properties of platelets during storage without the addition of red blood cells. Therefore it may offer a useful tool for future studies of platelet adhesive capacity in transfusion medicine and other settings.

  • 78.
    Tätting, Love
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Bernhardsson, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Different composition of leucocytes in cortical and cancellous bone healing in a mouse model2018In: Bone and Joint Research, ISSN 2046-3758, E-ISSN 2352-1872, Vol. 7, no 12, p. 620-628Article in journal (Refereed)
    Abstract [en]

    Objectives Cortical and cancellous bone healing processes appear to be histologically different. They also respond differently to anti-inflammatory agents. We investigated whether the leucocyte composition on days 3 and 5 after cortical and cancellous injuries to bone was different, and compared changes over time using day 3 as the baseline. Methods Ten-week-old male C56/B16J mice were randomized to either cancellous injury in the proximal tibia or cortical injury in the femoral diaphysis. Regenerating tissues were analyzed with flow cytometry at days 3 and 5, using panels with 15 antibodies for common macrophage and lymphocyte markers. The cellular response from day 3 to 5 was compared in order to identify differences in how cancellous and cortical bone healing develop. Results Between day 3 and 5, the granulocytes increased in the cancellous model, whereas the lymphocytes (T cells, B cells, NK cells) and monocytes (CD11b+, 14/80+, CD206+, CD14+ ) increased in the cortical model. Conclusion These results suggest an acute type of inflammation in cancellous bone healing, and a more chronic inflammation in cortical healing. This might explain, in part, why cancellous healing is faster and more resistant to anti-inflammatory drugs than are diaphyseal fractures.

  • 79.
    Tätting, Love
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Bernhardsson, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Isolated metaphyseal injury influences unrelated bones A flow cytometric study of tibia and humerus in mice2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 2, p. 223-230Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Fracture healing involves different inflammatory cells, some of which are not part of the traditional bone field, such as B-cells and cytotoxic T-cells. We wanted to characterize bone healing by flow cytometry using 15 different inflammatory cell markers in a mouse model of metaphyseal injury, and incidentally discovered a previously unknown general skeletal reaction to trauma. Material and methods - A bent needle was inserted and twisted to traumatize the cancellous bone in the proximal tibia of C57/Bl6 female mice. This is known to induce vivid bone formation locally in the marrow compartment. Cells were harvested from the injured region, the uninjured contralateral tibia, and the humerus. The compositions of the immune cell populations were compared to those in untraumatized control animals. Results - Tibial metaphyseal injury led to substantial changes in the cell populations over time. Unexpectedly, similar changes were also seen in the contralateral tibia and in the humerus, despite the lack of local trauma. Most leukocyte subsets were affected by this generalized reaction. Interpretation - A relatively small degree of injury to the proximal tibia led to systemic changes in the immune cell populations in the marrow of unrelated bones, and probably in the entire skeleton. The few changes that were specific for the injury site appeared to relate to modulatory functions.

  • 80.
    Vasilache, Ana-Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Qian, Hong
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Center for Hematology and Regenerative Medicine (HERM), Novum, Karolinska Institute, Huddinge, Sweden.
    Blomqvist, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Immune challenge by intraperitoneal administration of lipopolysaccharide directs gene expression in distinct blood-brain barrier cells toward enhanced prostaglandin E2 signaling2015In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 48, p. 31-41Article in journal (Refereed)
    Abstract [en]

    The cells constituting the blood-brain barrier are critical for the transduction of peripheral immune signals to the brain, but hitherto no comprehensive analysis of the signaling events that occur in these cells in response to a peripheral inflammatory stimulus has been performed. Here, we examined the inflammatory transcriptome in blood-brain barrier cells, including endothelial cells, pericytes, and perivascular macrophages, which were isolated by fluorescent-activated cell sorting, from non-immune-challenged mice and from mice stimulated by bacterial wall lipopolysaccharide. We show that endothelial cells and perivascular macrophages display distinct transcription profiles for inflammatory signaling and respond in distinct and often opposing ways to the immune stimulus. Thus, endothelial cells show induced PGE2 synthesis and transport with attenuation of PGE2 catabolism, increased expression of cytokine receptors and down-stream signaling molecules, and downregulation of adhesion molecules. In contrast, perivascular macrophages show downregulation of the synthesis of prostanoids other than PGE2 and of prostaglandin catabolism, but upregulation of interleukin-6 synthesis. Pericytes were largely unresponsive to the immune stimulation, with the exception of downregulation of proteins involved in pericyte-endothelial cell communication. While the endothelial cells account for most of the immune-induced gene expression changes in the blood-brain barrier, the response of the endothelial cells occurs in a concerted manner with that of the perivascular cells to elevate intracerebral levels of PGE2, hence emphasizing the critical role of PGE2 in immune-induced signal transduction across the blood-brain barrier.

  • 81.
    Velicky, Philipp
    et al.
    Med Univ Vienna, Austria; IST Austria, Austria.
    Meinhardt, Gudrun
    Med Univ Vienna, Austria.
    Plessl, Kerstin
    Med Univ Vienna, Austria; Univ Appl Sci, Austria.
    Vondra, Sigrid
    Med Univ Vienna, Austria.
    Weiss, Tamara
    St Anna Childrens Hosp, Austria; Med Univ Vienna, Austria.
    Haslinger, Peter
    Med Univ Vienna, Austria.
    Lendl, Thomas
    Inst Mol Biotechnol, Austria; Gregor Mendel Inst, Austria.
    Aumayr, Karin
    Inst Mol Biotechnol, Austria; Gregor Mendel Inst, Austria.
    Mairhofer, Mario
    Med Univ Vienna, Austria; Univ Appl Sci Upper Austria, Austria.
    Zhu, Xiaowei
    Stanford Univ, CA 94305 USA.
    Schuetz, Birgit
    Med Univ Vienna, Austria.
    Hannibal, Roberta L.
    Stanford Univ, CA USA; Second Genome, CA USA.
    Lindau, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Weil, Beatrix
    Med Univ Vienna, Austria.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Neesen, Juergen
    Med Univ Vienna, Austria.
    Egger, Gerda
    Med Univ Vienna, Austria.
    Mikula, Mario
    Med Univ Vienna, Austria.
    Roehrl, Clemens
    Med Univ Vienna, Austria.
    Urban, Alexander E.
    Stanford Univ, CA USA.
    Baker, Julie
    Stanford Univ, CA USA.
    Knoefler, Martin
    Med Univ Vienna, Austria.
    Pollheimer, Juergen
    Med Univ Vienna, Austria.
    Genome amplification and cellular senescence are hallmarks of human placenta development2018In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 14, no 10, article id e1007698Article in journal (Refereed)
    Abstract [en]

    Genome amplification and cellular senescence are commonly associated with pathological processes. While physiological roles for polyploidization and senescence have been described in mouse development, controversy exists over their significance in humans. Here, we describe tetraploidization and senescence as phenomena of normal human placenta development. During pregnancy, placental extravillous trophoblasts (EVTs) invade the pregnant endometrium, termed decidua, to establish an adapted microenvironment required for the developing embryo. This process is critically dependent on continuous cell proliferation and differentiation, which is thought to follow the classical model of cell cycle arrest prior to terminal differentiation. Strikingly, flow cytometry and DNAseq revealed that EVT formation is accompanied with a genome-wide polyploidization, independent of mitotic cycles. DNA replication in these cells was analysed by a fluorescent cell-cycle indicator reporter system, cell cycle marker expression and EdU incorporation. Upon invasion into the decidua, EVTs widely lose their replicative potential and enter a senescent state characterized by high senescence-associated (SA) beta-galactosidase activity, induction of a SA secretory phenotype as well as typical metabolic alterations. Furthermore, we show that the shift from endocycle-dependent genome amplification to growth arrest is disturbed in androgenic complete hydatidiform moles (CHM), a hyperplastic pregnancy disorder associated with increased risk of developing choriocarinoma. Senescence is decreased in CHM-EVTs, accompanied by exacerbated endoreduplication and hyperploidy. We propose induction of cellular senescence as a ploidy-limiting mechanism during normal human placentation and unravel a link between excessive polyploidization and reduced senescence in CHM.

  • 82.
    Warntjes, Marcel Jan Bertus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). SyntheticMR AB, Linkoping, Sweden.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Håkansson, Irene
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Improved Precision of Automatic Brain Volume Measurements in Patients with Clinically Isolated Syndrome and Multiple Sclerosis Using Edema Correction2018In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 39, no 2, p. 296-302Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The presence of edema will result in increased brain volume, which may obscure progressing brain atrophy. Similarly, treatment-induced edema reduction may appear as accelerated brain tissue loss (pseudoatrophy). The purpose of this study was to correlate brain tissue properties to brain volume, to investigate the possibilities for edema correction and the resulting improvement of the precision of automated brain volume measurements. MATERIALS AND METHODS: A group of 38 patients with clinically isolated syndrome or newly diagnosed MS were imaged at inclusion and after 1, 2, and 4 years using an MR quantification sequence. Brain volume, relaxation rates (R-1 and R-2), and proton density were measured by automated software. RESULTS: The reduction of normalized brain volume with time after inclusion was 0.273%/year. The mean SDs were 0.508%, 0.526%, 0.454%, and 0.687% at baseline and 1, 2, and 4 years. Linear regression of the relative change of normalized brain volume and the relative change of R-1, R-2, and proton density showed slopes of -0.198 (P amp;lt; .001), 0.156 (P = .04), and 0.488 (P amp;lt; .001), respectively. After we applied the measured proton density as a correction factor, the mean SDs decreased to 24.2%, 4.8%, 33.3%, and 17.4%, respectively. The observed atrophy rate reduced from 0.273%/year to 0.238%/year. CONCLUSIONS: Correlations between volume and R-1, R-2, and proton density were observed in the brain, suggesting that a change of brain tissue properties can affect brain volume. Correction using these parameters decreased the variation of brain volume measurements and may have reduced the effect of pseudoatrophy.

  • 83.
    Wickström, Anne
    et al.
    Umeå University, Sweden.
    Fagerström, Maria
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Rehabilitation Center.
    Wickström, Lucas
    Linköping University, Department of Computer and Information Science. Linköping University, Faculty of Science & Engineering.
    Granasen, Gabriel
    Umeå University, Sweden.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Sundstrom, Peter
    Umeå University, Sweden.
    The impact of adjusted work conditions and disease-modifying drugs on work ability in multiple sclerosis2017In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, no 8, p. 1137-1147Article in journal (Refereed)
    Abstract [en]

    Background: Multiple sclerosis (MS) is a neurological disorder that causes significantly reduced ability to work, and the Expanded Disability Status Scale (EDSS) is one of the main predictors for reduced work ability. Objectives: To investigate how work requirements, flexible work conditions and disease-modifying drugs (DMDs) influence the work ability in relation to different EDSS grades in two MS populations. Methods: Work ability was studied in two MS populations: one in the southern and one in the northern part of Sweden, both demographically similar. In the latter population, more active work-promoting interventions have been practised and second-generation DMDs have been widely used from the onset of disease for several years. Results: The proportion of MS patients who participated in the workforce or studied was significantly higher in the northern compared with the southern population (pamp;lt;0.001). The employees in the northern population had significantly lower requirements, greater adapted work conditions and were able to work more hours per week. Higher EDSS was associated with lower reduction in number of worked hours per week in the northern population (p=0.042). Conclusion: Our data indicated that treatment strategy and adjusted work conditions have impact on work ability in MS.

  • 84.
    Wågström, Per
    et al.
    Ryhov County Hospital, Jönköping, Sweden.
    Bengnér, Malin
    Ryhov County Hospital, Jönköping, Sweden.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Neumark, Thomas
    Primary Health in Lindsdal, Kalmar, Sweden.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Björkander, Janne
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Jönköping, Sweden.
    Does the frequency of respiratory tract infections help to identify humoral immunodeficiencies in a primary health-care cohort?2015In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 47, no 1, p. 13-19Article in journal (Refereed)
    Abstract [en]

    Background: Primary immune deficiency (PID) due to humoral defects is associated with recurrent respiratory tract infections (RTIs). Reliable clinical warning signs of PID would facilitate early diagnosis and thereby reduce long-term complications. The aim of the present study was to evaluate the accuracy of the warning sign, 'four or more antibiotic-treated RTIs annually for 3 or more consecutive years,' for detecting PID among adults in a primary health-care setting. Methods: Fifty-three cases with 'four or more antibiotic-treated RTIs annually for 3 or more consecutive years' were selected from a Swedish primary health-care registry of RTIs. In addition, 66 age- and sex-matched controls were selected having a maximum of one antibiotic-treated RTI during the period covered by the study. Levels of immunoglobulin (Ig) IgG, IgA, IgM, IgG subclasses, and IgG antibodies against Haemophilus influenzae and Streptococcus pneumoniae as well as the inflammatory markers, C-reactive protein, interleukin (IL)-6 and IL-8 were determined. Results: IgG subclass deficiencies (IgGsd) were found in 5/53 (9.4%) of the cases and in 7/66 (10.6%) controls. The most frequent deficiency was IgG3sd and this was found in three participants in the case group and seven in the control group. The mean level of IgG3 was lower in the control group (p = 0.02). The mean level of IL-8 was lower in the case group (p = 0.02). Conclusion: The results show that physicians working in primary health care cannot solely rely on the frequency of antibiotic-treated RTIs as a warning sign for the detection of common humoral immune deficiencies.

  • 85.
    Wågström, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Yamada, Naomi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bengner, Malin
    Ryhov Cty Hosp, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Björkander, Jan Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Fc gamma-receptor polymorphisms associated with clinical symptoms in patients with immunoglobulin G subclass deficiency2018In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 50, no 11-12, p. 853-858Article in journal (Refereed)
    Abstract [en]

    Background: Immunoglobulin G subclass deficiencies (IgGsd) are associated with recurrent respiratory tract infections. Immunoglobulin substitution therapy may be needed to prevent chronic lung tissue damage but tools for identifying the patients that will benefit from this treatment are still insufficient. Some Fc gamma R polymorphisms seem to predispose for an increased risk for infections. In this study we wanted to evaluate if the Fc gamma R-profile differs between individuals with IgGsd and a control population. Methods: Single nucleotide polymorphisms (SNPs) of Fc gamma RIIa, Fc gamma RIIIa and Fc gamma RIIc in 36 IgGsd patients and 192 controls with similar sex and geographical distribution were analyzed by TaqMan allelic discrimination assay or Sanger sequencing. Results: In the IgGsd-group, homozygous frequency for Fc gamma RIIa-R/R131 (low-binding capacity isoform) was higher (p = .03) as well as for non-classical Fc gamma RIIc-ORF (p = .03) and classical Fc gamma RIIc-ORF tended (p = .07) to be more common compared to the controls. There was no difference between the groups regarding Fc gamma RIIIa. Conclusion: The gene for classical Fc gamma RIIc-ORF tended to be more frequent in individuals with immunoglobulin G subclass deficiency and the genes for non-classical Fc gamma RIIc-ORF as well as low-binding capacity receptor Fc gamma RIIa-R/R131 were more frequent. Further studies on the Fc gamma R polymorphisms may pave way for identifying individuals that will benefit from immunoglobulin substitution.

  • 86.
    Zeka, Bleranda
    et al.
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Hastermann, Maria
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Kaufmann, Nathalie
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Schanda, Kathrin
    Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
    Pende, Marko
    Medical University Vienna, Section for Bioelectronics, Center for Brain Research, Vienna, Austria.
    Misu, Tatsuro
    Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
    Rommer, Paulus
    Department of Neurology, Medical University Vienna, Wien, Austria.
    Fujihara, Kazuo
    Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
    Nakashima, Ichiro
    Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Leutmezer, Fritz
    Department of Neurology, Medical University Vienna, Wien, Austria.
    Reindl, Markus
    Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
    Lassmann, Hans
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Bradl, Monika
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Aquaporin 4-specific T cells and NMO-IgG cause primary retinal damage in experimental NMO/SD.2016In: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 4, no 1, article id 82Article in journal (Refereed)
    Abstract [en]

    Neuromyelitis optica/spectrum disorder (NMO/SD) is a severe, inflammatory disease of the central nervous system (CNS). In the majority of patients, it is associated with the presence of pathogenic serum autoantibodies (the so-called NMO-IgGs) directed against the water channel aquaporin 4 (AQP4), and with the formation of large, astrocyte-destructive lesions in spinal cord and optic nerves. A large number of recent studies using optical coherence tomography (OCT) demonstrated that damage to optic nerves in NMO/SD is also associated with retinal injury, as evidenced by retinal nerve fiber layer (RNFL) thinning and microcystic inner nuclear layer abnormalities. These studies concluded that retinal injury in NMO/SD patients results from secondary neurodegeneration triggered by optic neuritis.However, the eye also contains cells expressing AQP4, i.e., Müller cells and astrocytes in the retina, epithelial cells of the ciliary body, and epithelial cells of the iris, which raised the question whether the eye can also be a primary target in NMO/SD. Here, we addressed this point in experimental NMO/SD (ENMO) induced in Lewis rat by transfer of AQP4268-285-specific T cells and NMO-IgG.We show that these animals show retinitis and subsequent dysfunction/damage of retinal axons and neurons, and that this pathology occurs independently of the action of NMO-IgG. We further show that in the retinae of ENMO animals Müller cell side branches lose AQP4 reactivity, while retinal astrocytes and Müller cell processes in the RNFL/ganglionic cell layers are spared. These changes only occur in the presence of both AQP4268-285-specific T cells and NMO-IgG.Cumulatively, our data show that damage to retinal cells can be a primary event in NMO/SD.

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