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Good, E., Åkerman, L., Nyström, S. N., Jonasson, L., Ernerudh, J. & de Muinck, E. (2023). Changes in natural killer and T lymphocyte phenotypes in response to cardiovascular risk management. Scientific Reports, 13(1), Article ID 20810.
Open this publication in new window or tab >>Changes in natural killer and T lymphocyte phenotypes in response to cardiovascular risk management
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2023 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 20810Article in journal (Refereed) Published
Abstract [en]

The pro-inflammatory and regulatory roles of T lymphocytes in atherosclerosis are well established but less is known about natural killer (NK) cells and natural killer T (NKT)-like cells. The effects of cardiovascular risk management on the phenotypes of these cells are unknown. To assess changes in NK cell and lymphocyte phenotypes and circulating inflammatory proteins in response to cardiovascular risk management in patients with carotid atherosclerosis. Fifty patients were included in a prospective clinical study. Measurements were at baseline and after 12 months of cardiovascular risk management. Circulating NK, NKT-like and T lymphocyte subpopulations were phenotyped by multi-colour flow cytometry. Proximity extension assay was performed for 176 plasma proteins associated with inflammation and cardiovascular disease. At 12 months there were significant reductions in LDL (P=0.001) and blood pressure (P=0.028). NK cells responded with a reduction in pro-inflammatory (NKG2C(+)) cells (P=0.0003), an increase in anti-inflammatory (NKG2A(+)) cells (P=0.032), and a reduction in terminally differentiated (CD57(+)) NK cells. NKT-like cells showed a similar decrease in terminally differentiated subpopulations (P=0.000002). Subpopulations of T helper cells exhibited a significant reduction in central memory (P=1.09x10(-8)) and a significant increase in CD4(+) naive- (P=0.0008) and effector memory T cells (P=0.006). The protein analysis indicated that cardiovascular risk management affects proteins involved in the inflammatory NF-kappa B pathway. The consistent decrease in senescent phenotypes of NK, NKT-like and CD4(+) cells with a concomitant increase in more naive, phenotypes suggests a change towards a less pro-inflammatory lymphocyte profile in response to cardiovascular risk management.Trial registry name: CARotid MRI of Atherosclerosis (CARMA). ClinicalTrials.gov identifier NCT04835571 (08/04/2021). https://www.clinicaltrials.gov/study/NCT04835571.

Place, publisher, year, edition, pages
Nature Publishing Group, 2023
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-200751 (URN)10.1038/s41598-023-48111-7 (DOI)001144297500084 ()38012327 (PubMedID)
Note

Funding Agencies|Linkoping University; Region Ostergotland [RO-610581]; Henry och Ella Margareta Stahls Stiftelse (Henry and Ella Margareta Stahl's Foundation) [LIO-748491]; Forskningsradet i Sydostra Sverige [FORSS-756191]

Available from: 2024-02-07 Created: 2024-02-07 Last updated: 2024-02-07
Gustafsson, M., Ernerudh, J. & Olsson, T. (2023). Data for: Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis.
Open this publication in new window or tab >>Data for: Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis
2023 (English)Data set
Abstract [en]

Protein levels were measured in cerebrospinal fluid samples (CSF; n = 186) and plasma samples (n = 165) from persons with multiple sclerosis and healthy controls. CSF samples and plasma samples were taken from 92 persons with CIS or RRMS at Linköping University Hospital, Sweden and 51 persons with CIS or RRMS at the Karolinska University Hospital, Sweden. Everyone fulfilled the revised McDonald criteria from 2010 and 2017 for CIS or Multiple sclerosis (MS). Age-matched healthy controls (HC) were recruited from healthy blood donors (23 at the Linköping University hospital and 20 at the Karolinska University Hospital). The concentration of 1463 proteins were measured using the Olink Explore platform which uses Proximity Extension Assay (PEA) technology. The proteins were preselected from four Olink panels: Explore 384 Cardiometabolic, Explore 384 Inflammation, Explore 384 Neurology, and Explore 384 Oncology. The protein concentrations are given as Olink’s relative protein quantification unit on log2 scale: Normalized Protein Expression (NPX). The NPX values were intensity normalized by Olink.

Keywords
multiple sclerosis, proteomics
National Category
Neurology Bioinformatics and Systems Biology Bioinformatics (Computational Biology) Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-198043 (URN)10.48360/jcps-gw67 (DOI)
Note

For access to dataset, please contact mika.gustafsson@liu.se for further information.

Research funders:

Swedish Foundation for Strategic Research (SB16-0011)

Swedish Brain Foundation

Knut and Alice Wallenberg Foundation

Margareth AF Ugglas Foundation

Swedish Research Council (2019-04193, 2018-02776, 2020-02700, 2021-03092)

Swedish Knowledge Foundation (2020-0014)

Medical Research Council of Southeast Sweden (FORSS-315121)

NEURO Sweden (F2018-0052)

ALF grants

Region Östergötland

Swedish Foundation for MS Research

European Union's  Marie Sklodowska-Curie (813863)

Available from: 2023-09-22 Created: 2023-09-22 Last updated: 2024-03-11
Åkesson, J., Hojjati, S., Hellberg, S., Raffetseder, J., Khademi, M., Rynkowski, R., . . . Gustafsson, M. (2023). Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis. Nature Communications, 14(1), Article ID 6903.
Open this publication in new window or tab >>Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis
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2023 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1, article id 6903Article in journal (Refereed) Published
Abstract [en]

Sensitive and reliable protein biomarkers are needed to predict disease trajectory and personalize treatment strategies for multiple sclerosis (MS). Here, we use the highly sensitive proximity-extension assay combined with next-generation sequencing (Olink Explore) to quantify 1463 proteins in cerebrospinal fluid (CSF) and plasma from 143 people with early-stage MS and 43 healthy controls. With longitudinally followed discovery and replication cohorts, we identify CSF proteins that consistently predicted both short- and long-term disease progression. Lower levels of neurofilament light chain (NfL) in CSF is superior in predicting the absence of disease activity two years after sampling (replication AUC = 0.77) compared to all other tested proteins. Importantly, we also identify a combination of 11 CSF proteins (CXCL13, LTA, FCN2, ICAM3, LY9, SLAMF7, TYMP, CHI3L1, FYB1, TNFRSF1B and NfL) that predict the severity of disability worsening according to the normalized age-related MS severity score (replication AUC = 0.90). The identification of these proteins may help elucidate pathogenetic processes and might aid decisions on treatment strategies for persons with MS.

Place, publisher, year, edition, pages
NATURE PORTFOLIO, 2023
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-199196 (URN)10.1038/s41467-023-42682-9 (DOI)001129872400021 ()37903821 (PubMedID)
Note

Funding: The study was funded by the Swedish Foundation for Strategic Research (SB16-0011 [M.G., J.E.]), the Swedish Brain Foundation, Knut and Alice Wallenberg Foundation, and Margareth AF Ugglas Foundation, Swedish Research Council (2019-04193 [M.G.], 2018-02776 [J.E.], 2020-02700 [F.P.], 2020-00014 [Z.L.P.], 2021-03092 [J.E.]), the Medical Research Council of Southeast Sweden (FORSS-315121 [J.E.]), NEURO Sweden (F2018-0052 [J.E.]), ALF grants, Region Östergötland, the Swedish Foundation for MS Research and the European Union’s Marie Sklodowska-Curie (813863 [J.E.]). The authors would like to acknowledge support of the Clinical biomarker facility at SciLifeLab Sweden for providing assistance in protein analyses.

Available from: 2023-11-16 Created: 2023-11-16 Last updated: 2024-03-11Bibliographically approved
Appelgren, D., Puli, S., Hellmark, T., Pochard, P., Pers, J.-O., Ernerudh, J., . . . Segelmark, M. (2023). Regulatory B cells are reduced in the blood in patients with granulomatosis with polyangiitis, and fail to regulate T-cell IFN-γproduction. Clinical and Experimental Immunology, 213(2), 190-201
Open this publication in new window or tab >>Regulatory B cells are reduced in the blood in patients with granulomatosis with polyangiitis, and fail to regulate T-cell IFN-γproduction
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2023 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 213, no 2, p. 190-201Article in journal (Refereed) Published
Abstract [en]

Regulatory B (Breg) cells can dampen inflammation, autoreactivity, and transplant rejection. We investigated the frequencies, phenotypes, and function of Breg cells in granulomatosis with polyangiitis (GPA) to gain further knowledge as to whether there are numerical alterations or limitations of their ability to regulate T-cell function. Frequencies and phenotypes of CD24hiCD27+ and CD24hiCD38hi B-cells in the blood were determined with flow cytometry in 37 GPA patients (22 in remission and 15 with active disease) and 31 healthy controls (HC). A co-culture model was used to study the capacity of Breg cells to regulate T-cell activation and proliferation in cells from 10 GPA patients in remission and 12 HC. T-cell cytokine production in vitro and levels in plasma were determined with enzyme-linked immunosorbent assay. Frequencies of CD24hiCD27+ B-cells were reduced both during active disease and remission compared with HC (P = 0.005 and P = 0.010, respectively), whereas CD24hiCD38hi B-cells did not differ. Patient CD24hiCD27+ B-cells exhibited decreased expression of CD25 but increased expression of PD-L1 and PD-L2 during remission. B-cells from GPA patients regulated T-cell proliferation but failed to regulate interferon (IFN)-γproduction (median T-cells alone 222 ng/ml vs. T-cells + B-cells 207 ng/ml, P = 0.426). IFN-γwas also elevated in patient plasma samples (P = 0.016). In conclusion, GPA patients exhibit altered numbers and phenotypes of CD24hiCD27+ B-cells. This is accompanied by a disability to control T-cell production of Th1-type cytokines during remission, which might be of fundamental importance for the granulomatous inflammation that characterizes the chronic phase of this disease. © 2023 The Author(s). Published by Oxford University Press on behalf of the British Society for Immunology.

Place, publisher, year, edition, pages
Oxford University Press, 2023
Keywords
B-Lymphocytes, Regulatory; Cytokines; Granulomatosis with Polyangiitis; Humans; Inflammation; Interferon-gamma; azathioprine; CD24 antigen; CD27 antigen; chemokine; cyclophosphamide; cytokine; gamma interferon; interleukin 2 receptor; interleukin 2 receptor alpha; methotrexate; mycophenolate mofetil; myeloperoxidase; prednisolone; programmed death 1 ligand 1; rituximab; cytokine; gamma interferon; adult; aged; Article; autoimmunity; B lymphocyte; B lymphocyte subpopulation; cell function; cell population; cell proliferation; clinical article; coculture; comparative study; controlled study; cytokine production; disease activity; enzyme linked immunosorbent assay; female; flow cytometry; follow up; gene expression; gene frequency; human; human cell; immunoregulation; in vitro study; male; middle aged; peripheral blood mononuclear cell; phenotype; proliferation index; protein expression; regulatory B lymphocyte; regulatory mechanism; remission; T lymphocyte; T lymphocyte activation; treatment failure; vasculitis; Wegener granulomatosis; inflammation; metabolism
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-200766 (URN)10.1093/cei/uxad021 (DOI)36752779 (PubMedID)2-s2.0-85165521399 (Scopus ID)
Available from: 2024-02-07 Created: 2024-02-07 Last updated: 2024-02-07
Edvardsson, M., Sund-Levander, M., Milberg, A., Ernerudh, J., Wressle, E., Marcusson, J. & Grodzinsky, E. (2022). Classification of ≥80-year-old individuals into healthy, moderately healthy, and frail based on different frailty scores affects the interpretation of laboratory results. Asian Journal of Medical Sciences, 13(9), 63-71
Open this publication in new window or tab >>Classification of ≥80-year-old individuals into healthy, moderately healthy, and frail based on different frailty scores affects the interpretation of laboratory results
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2022 (English)In: Asian Journal of Medical Sciences, ISSN 2091-0576, E-ISSN 2091-0576, Vol. 13, no 9, p. 63-71Article in journal (Refereed) Published
Abstract [en]

Background: Interpretation laboratory analyses are crucial when assessing the patient’s condition. Reference intervals from apparently healthy and disease-free individuals may cause problems when outcomes from elderly patients with chronic diseases and on medications are being interpreted. Elderly individuals are a heterogeneous group ranging from individuals managing their daily life independently to individuals with diseases and impairment, in need of nursing care around the clock, that is, frail; a term widely used although there is no consensus on the definition.

Aims and Objectives: The aim of the study was to study the effect of classification of elderly into healthy, moderately healthy, and frail, based on activities of daily living (ADL) and Mini-Mental State Examination (MMSE) or frailty index (FI), on the interpretation of outcomes regarding: Albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and gamma-glutamyltransferase (γ-GT) levels.

Materials and Methods: Individuals ≥80 years (n=568) were classified either on ADL and MMSE or number of deficits, (FI).

Results: Individuals classified as frail based on FI had lower mean levels for ALT, creatinine and γ-GT than individuals classified based on ADL and MMSE (P<0.05).

Conclusion: The model to define health status to some extent affected laboratory analyte levels in ≥80 years old, classified as healthy, moderately healthy, and frail based on ADL and MMSE versus FI.

Place, publisher, year, edition, pages
Nepal Journals Online (NepJOL), 2022
Keywords
Aging; Frail elderly; Analyte; Reference interval; Clinical interpretation
National Category
Geriatrics Clinical Laboratory Medicine
Identifiers
urn:nbn:se:liu:diva-192092 (URN)10.3126/ajms.v13i9.45298 (DOI)
Available from: 2023-03-01 Created: 2023-03-01 Last updated: 2023-03-02
Huoman, J., Martinez-Enguita, D., Olsson, E., Ernerudh, J., Nilsson, L., Duchén, K., . . . Jenmalm, M. (2021). Combined prenatal Lactobacillus reuteri and omega-3 supplementation synergistically modulates DNA methylation in neonatal T helper cells. Clinical Epigenetics, 13(1), Article ID 135.
Open this publication in new window or tab >>Combined prenatal Lactobacillus reuteri and omega-3 supplementation synergistically modulates DNA methylation in neonatal T helper cells
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2021 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, Clinical Epigenetics, ISSN 1868-7075, Vol. 13, no 1, article id 135Article in journal (Refereed) Published
Abstract [en]

BackgroundEnvironmental exposures may alter DNA methylation patterns of T helper cells. As T helper cells are instrumental for allergy development, changes in methylation patterns may constitute a mechanism of action for allergy preventive interventions. While epigenetic effects of separate perinatal probiotic or omega -3 fatty acid supplementation have been studied previously, the combined treatment has not been assessed. We aimed to investigate epigenome-wide DNA methylation patterns from a sub-group of children in an on-going randomised double-blind placebo-controlled allergy prevention trial using pre- and postnatal combined Lactobacillus reuteri and omega -3 fatty acid treatment. To this end,&gt;866000 CpG sites (MethylationEPIC 850K array) in cord blood CD4+ T cells were examined in samples from all four study arms (double-treatment: n=18, single treatments: probiotics n=16, omega -3 n=15, and double placebo: n=14). Statistical and bioinformatic analyses identified treatment-associated differentially methylated CpGs and genes, which were used to identify putatively treatment-induced network modules. Pathway analyses inferred biological relevance, and comparisons were made to an independent allergy data set.ResultsComparing the active treatments to the double placebo group, most differentially methylated CpGs and genes were hypermethylated, possibly suggesting induction of transcriptional inhibition. The double-treated group showed the largest number of differentially methylated CpGs, of which many were unique, suggesting synergy between interventions. Clusters within the double-treated network module consisted of immune-related pathways, including T cell receptor signalling, and antigen processing and presentation, with similar pathways revealed for the single-treatment modules. CpGs derived from differential methylation and network module analyses were enriched in an independent allergy data set, particularly in the double-treatment group, proposing treatment-induced DNA methylation changes as relevant for allergy development.ConclusionPrenatal L. reuteri and/or omega -3 fatty acid treatment results in hypermethylation and affects immune- and allergy-related pathways in neonatal T helper cells, with potentially synergistic effects between the interventions and relevance for allergic disease. Further studies need to address these findings on a transcriptional level, and whether the results associate to allergy development in the children. Understanding the role of DNA methylation in regulating effects of perinatal probiotic and omega -3 interventions may provide essential knowledge in the development of efficacious allergy preventive strategies.Trial registration ClinicalTrials.gov, ClinicalTrials.gov-ID: NCT01542970. Registered 27th of February 2012-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01542970.

Place, publisher, year, edition, pages
BMC, 2021
Keywords
Allergy prevention; Combined intervention; Cord blood; CD4+T cells; DNA methylation; Lactobacillus reuteri; MethylationEPIC 850K; omega-3 fatty acids; Prenatal; Postnatal
National Category
Psychiatry
Identifiers
urn:nbn:se:liu:diva-180073 (URN)10.1186/s13148-021-01115-4 (DOI)000670704300003 ()34193262 (PubMedID)
Note

Funding Agencies|Linkoping University; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2016-01698, 201900989]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20140321, 20170365]; Cancer and Allergy Foundation; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [FORSS-666771, FORSS-758981]

Available from: 2021-10-08 Created: 2021-10-08 Last updated: 2024-01-28
Svenvik, M., Raffetseder, J., Brudin, L., Lindberg, R., Blomberg, M., Axelsson, D., . . . Nording, M. L. (2021). Plasma oxylipin levels associated with preterm birth in preterm labor✰. Prostaglandins, Leukotrienes and Essential Fatty Acids, 166, Article ID 102251.
Open this publication in new window or tab >>Plasma oxylipin levels associated with preterm birth in preterm labor✰
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2021 (English)In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 166, article id 102251Article in journal (Refereed) Published
Abstract [en]

Introduction

Preterm labor is a common clinical problem in obstetrics. Since the majority of women with preterm labor eventually deliver at full term, biomarkers are needed to more accurately predict who will deliver preterm. Oxylipins, given their importance in inflammation regulation, are highly interesting in this respect since labor is an inflammatory process.

Methods

Eighty women with preterm labor before 34 weeks of gestation were enrolled in a prospective observational multi-center cohort study. Oxylipin levels of 67 analytes in plasma samples were analyzed by liquid chromatography coupled to tandem mass spectrometry.

Results

Twenty-one (26%) of the women delivered before 34 weeks of gestation, and of those women, fourteen delivered within 48 h of admission. Logistic multivariate regression showed that lower levels of 9,10-DiHODE were associated with delivery before 34 weeks of gestation (aOR 0.12 (0.024–0.62)) and within 48 h ((aOR 0.13 (0.019–0.93)). Furthermore, higher levels of 11,12-DiHETrE were associated with delivery before 34 weeks of gestation ((aOR 6.19 (1.17–32.7)) and higher levels of 8-HETE were associated with delivery within 48 h ((aOR 5.01 (1.13–22.14)).

Conclusions

The oxylipin 9,10-DiHODE may be protective in preterm labor, both for delivery after 34 weeks of gestation and for delivery later than 48 h of admission, whereas 11,12-DiHETrE and 8-HETE display the opposite effect. Larger studies are needed to validate these mediators as biomarkers for prediction of preterm birth following preterm labor.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
Preterm labor, Preterm birth, Oxylipins, Eicosanoids, Biomarker, Prediction
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:liu:diva-174827 (URN)10.1016/j.plefa.2021.102251 (DOI)000633428800004 ()33626402 (PubMedID)2-s2.0-85101321594 (Scopus ID)
Note

Medical Research Council of Southeast Sweden (FORSS) [FORSS-931816]; Region Kalmar County; ALF grants; Region Ostergotland

Available from: 2021-04-06 Created: 2021-04-06 Last updated: 2022-01-23Bibliographically approved
Roepke, E. R., Bruno, V., Nedstrand, E., Boij, R., Strid, C. P., Piccione, E., . . . Ernerudh, J. (2020). Author Correction: Low-molecular-weight-heparin increases Th1- and Th17-associated chemokine levels during pregnancy in women with unexplained recurrent pregnancy loss: a randomised controlled trial. Scientific Reports, 10(1)
Open this publication in new window or tab >>Author Correction: Low-molecular-weight-heparin increases Th1- and Th17-associated chemokine levels during pregnancy in women with unexplained recurrent pregnancy loss: a randomised controlled trial
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2020 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1Article in journal (Other academic) Published
Place, publisher, year, edition, pages
Nature Publishing Group, 2020
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:liu:diva-174298 (URN)10.1038/s41598-020-67807-8 (DOI)000546578200015 ()32587333 (PubMedID)2-s2.0-85087047490 (Scopus ID)
Note

Correction to: Scientifc Reports https://doi.org/10.1038/s41598-019-48799-6

Available from: 2021-03-18 Created: 2021-03-18 Last updated: 2023-12-22Bibliographically approved
Håkansson, I., Ernerudh, J., Vrethem, M., Dahle, C. & Ekdahl, K. N. (2020). Complement activation in cerebrospinal fluid in clinically isolated syndrome and early stages of relapsing remitting multiple sclerosis. Journal of Neuroimmunology, 340, Article ID 577147.
Open this publication in new window or tab >>Complement activation in cerebrospinal fluid in clinically isolated syndrome and early stages of relapsing remitting multiple sclerosis
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2020 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 340, article id 577147Article in journal (Refereed) Published
Abstract [en]

To assess if markers of complement activation are associated with disease activity, C1q, C3, C3a and sC5b-9 levels in plasma and cerebrospinal fluid (CSF) were determined in 41 patients with clinically isolated syndrome (CIS) or remitting multiple sclerosis (RRMS), in a prospective longitudinal four-year cohort study. C1q in CSF (CSF-C1q) was significantly higher in patients than in controls. Baseline CSF-C1q and CSF-C3a correlated with several neuroinflammatory markers and neurofilament light chain levels. Baseline CSF-C3a correlated with the number of T2 lesions at baseline and new T2 lesions during follow-up. Baseline CSF-C3a was also significantly higher in patients with (n = 21) than in patients without (n = 20) signs of disease activity according to the NEDA-3 concept during one year of follow-up (p ≤ .01) Study results support that complement activation is involved in MS pathophysiology and that CSF-C3a carries prognostic information.

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
Complement system, C1q, C3a, Multiple sclerosis, Clinically isolated syndrome, Disease activity
National Category
Neurology Rheumatology and Autoimmunity Clinical Laboratory Medicine
Identifiers
urn:nbn:se:liu:diva-163143 (URN)10.1016/j.jneuroim.2020.577147 (DOI)000514757300005 ()
Note

Funding agencies:  Medical Research Council of Southeast Sweden (FORSS); NEURO Sweden; Swedish Research CouncilSwedish Research Council [K2013-61X-22310-01-4, 2016-2075-5.1]; ALF grants, Region Ostergotland; Linnaeus University

Available from: 2020-01-16 Created: 2020-01-16 Last updated: 2021-04-29Bibliographically approved
Hamrin, E., Ernerudh, J. & Rosén, A. (2018). Immunological and Quality-of-Life Profiles in Women with Breast Cancer: Complementary versus Conventional Care. Complementary Medicine Research, 25, 391-397
Open this publication in new window or tab >>Immunological and Quality-of-Life Profiles in Women with Breast Cancer: Complementary versus Conventional Care
2018 (English)In: Complementary Medicine Research, ISSN 2504-2092, Vol. 25, p. 391-397Article in journal (Refereed) Published
Abstract [en]

Background: Previous studies showed that women with breast cancer treated in anthroposophic clinic versus conventional care had increased quality of life (QoL) parameters, fighting spirit, and anxiety coping. We have now analyzed immune and QoL factors in these 2 groups for possible differences during the first 6 months after admission, prompted by anthroposophic studies, including mistletoe extracts, showing beneficial immune system effects.

Patients and MethodsFourteen immunological variables, including leukocyte count, lymphocyte count, activated T cells (CD4+ and CD8+), NK cells, B cells, IL1β, IL6, IL10, and oxytocin, were longitudinally analyzed in both groups (n = 2 × 26). A panel of QoL parameters were analyzed using 3 different instruments. Statistical evaluation included that each patient was its own control.

Results: Cytotoxic CD8+ T cell frequency (percent of lymphocytes analyzed by flow-cytometry) significantly decreased over time in the anthroposophic group versus the conventional group (repeated measures ANOVA, p = 0.05). No major differences were observed in other immunological parameters, whereas QoL variables, anxiety decreased and physical symptoms increased/improved significantly in the anthroposophic group (p = 0.04 and p = 0.05, respectively).

Conclusion: Overall, women with breast cancer in anthroposophic or conventional therapy did not differ in their immune profiles over time, with exception of decreased cytotoxic T cells in the anthroposophic group. Improvement in physical symptoms along with less anxiety in this group may have influenced the brain-immune axis resulting in lower frequency of CD8+ T cells, a feature associated with less aggressive cancer stages. To evaluate whether this observation is associated with good or bad prognosis, further detailed analyses of memory and naïve CD8+ T cells at tumor site and in blood circulation are essential.

Abstract [de]

Hintergrund: Bisherige Studien haben gezeigt, dass die Behandlung von Brustkrebspatientinnen in anthroposophischen Kliniken gegenüber einer konventionellen Behandlung mit einer verbesserten Lebensqualität (quality of life; QoL), größerem Kampfgeist und einer besseren Angstbewältigung einhergeht. Angespornt durch anthroposophische Studien, solche mit Mistelextrakt eingeschlossen, die eine günstige Wirkung auf das Immunsystem zeigten, haben wir nun Immun- und QoL-Faktoren in diesen beiden Gruppen während der ersten 6 Monate nach Aufnahme untersucht.

Patienten und Methoden: 14 immunologische Variablen, einschließlich Leukozyten- und Lymphozytenzahl, aktivierter T-Zellen (CD4+ und CD8+), NK-Zellen, B-Zellen, IL1β, IL6, IL10 und Oxytocin, wurden in beiden Gruppen longitudinal analysiert (n = 2 × 26). Unter Zuhilfenahme von 3 verschiedenen Instrumenten wurde eine Reihe von QoL-Parametern analysiert. Die statistische Auswertung war so angelegt, dass jeder Patient als seine eigene Kontrolle diente.

Ergebnisse: Die Häufigkeit von zytotoxischen CD8+-T-Zellen (prozentualer Anteil an Lymphozyten analysiert mittels Durchflusszytometrie) nahm in der anthroposophischen gegenüber der konventionell behandelten Gruppe im Zeitverlauf signifikant ab (wiederholte ANOVA-Messungen; p = 0,05). Während für weitere immunologische Parameter keine größeren Unterschiede festgestellt wurden, verbesserten sich die QoL-Variablen; die Angst verringerte sich und die physischen Symptome verbesserten sich signifikant in der anthroposophischen Gruppe (p = 0,04 bzw. p = 0,05).

Schlussfolgerung: Insgesamt zeigte sich, dass es während des untersuchten Zeitraums keinen Unterschied in den Immunprofilen von Brustkrebspatientinnen mit anthroposophischer gegenüber solchen mit ausschließlich konventioneller Therapie gab. Die Verbesserung der physischen Symptome sowie die verringerte Angst in dieser Gruppe könnte die Gehirnimmunachse beeinflusst und zu einer geringeren Häufigkeit der CD8+-T-Zellen, einem Kennzeichen für weniger aggressive Tumorstadien, geführt haben. Um beurteilen zu können, ob diese Beobachtung mit einer guten oder schlechten Prognose assoziiert ist, sind weitere detaillierte Untersuchungen von Gedächtnis- und naiven CD8+-T-Zellen am Tumorort und in der Blutzirkulation unerlässlich.

Place, publisher, year, edition, pages
S. Karger, 2018
Keywords
Breast cancer treatment, Complementary medicine, Anthroposophical care, Immunology, Tumor immunity, Cytotoxic CD8 + T cells, Physical symptoms, Anxiety, Brustkrebstherapie, Komplementärmedizin, Anthroposophische Versorgung, Immunologie, Tumorimmunität, Zytotoxische CD8+-T-Zellen, Physische Symptome, Angst
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-153754 (URN)10.1159/000490049 (DOI)000456452900009 ()30145583 (PubMedID)2-s2.0-85053163476 (Scopus ID)
Funder
Swedish Cancer Society
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2020-01-16Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9456-2044

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