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  • 1.
    Hedin Skogman, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Neuroborreliosis in childhood: Clinical, immunological and diagnostic aspects2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Lyme Borreliosisis is a multi-organ infectious disease caused by the spirochete Borrelia burgdorferi. The spirochete is transmitted to humans by tick bites. Neuroborreliosis (NB) is a disseminated form of the disease, in which the spirochetes invade the nervous system. In children, subacute meningitis and facial nerve palsy are typical clinical manifestations of NB.

    The aim of this thesis was to study clinical, immunological and laboratory characteristics in children being evaluated for NB in a Lyme endemic area of Sweden, in order to identify factors of importance for prognosis and clinical recovery. A total of 250 patients and 220 controls were included during 1998-2005, with a prospective and a retrospective part.

    Less than half (41%) of children with signs and symptoms indicative of NB get the diagnosis confirmed by detection of Borrelia specific flagella antibodies in CSF (clinical routine method). Surprisingly few patients were diagnosed as having other infectious or neurologic diseases and consequently, many patients ended up with an uncertain diagnosis. However, four new Borrelia antigens (DbpA, BBK32, OspC, IR6) were evaluated and performed well in laboratory diagnostics. If they were combined in a panel, together with the flagella antigen, the sensitivity was 82% and the specificity 100%, leading to improved diagnostic accuracy in children with NB, as compared to using the routine flagella antibody test alone.

    Clinical recovery at the 6-month follow-up (n=177) was generally good and nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. No patient was found to have recurrent or progressive neurologic symptoms.

    However, permanent facial nerve palsy was found in 22% of patients at the 2-year follow-up, with consequences such as eye-closing problems, excessive tear secretion, pronunciation difficulties and cosmetic complaints.

    When cellular immune responses were investigated, the number of Borrelia-specific IL-4 and IFN-γ secreting cells in CSF was found to be more prominent in children with NB than in controls. Furthermore, a much stronger IL-4 response in CSF was seen in children as compared to adults with NB. This cytokine profile of children with NB is believed to represent an effective and balanced type1/type2 response in a relevant compartment, and could contribute to the less severe course of the disease seen in children as compared to adults with NB.

    No prognostic factors were found to influence the outcome in patients with “Confirmed NB” or facial nerve palsy. Nor was any specific cytokine profile, or antibody response to new Borrelia antigens in CSF, correlated to a less favorable clinical outcome.

    An NB prediction score test, based on clinical variables at admission, is suggested to help physicians to determine whether to start early antibiotic treatment, before results from Borrelia antibody tests are available.

    Results in this thesis support the notion that mononuclear pleocytosis in CSF, in patients being evaluated for NB, indicates that they are true NB cases despite the fact that an antibody response cannot yet be visualized. with the routine flagella test. Consequently, early antibiotic treatment in NB seems to be the correct course of action and over-treatment is not a substantial problem.

    List of papers
    1. Acute facial palsy in children - a 2-year follow-up study with focus on Lyme neuroborreliosis
    Open this publication in new window or tab >>Acute facial palsy in children - a 2-year follow-up study with focus on Lyme neuroborreliosis
    2003 (English)In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, Vol. 67, no 6, p. 597-602Article in journal (Refereed) Published
    Abstract [en]

    Objective: Acute facial palsy in children is believed to be a rather benign neurological condition. Follow-up-studies are sparse, especially including a thorough otoneurological re-examination. The aim of this study was to examine children with a history of facial palsy in order to register the incidence of complete recovery and the severity and nature of sequelae. We also wanted to investigate whether there was a correlation between sequelae and Lyme Borreliosis, treatment or other health problems.

    Methods: Twenty-seven children with a history of facial palsy were included. A re-examination was performed by an Ear-Nose-Throat (ENT) specialist 1–2.9 years (median 2) after the acute facial palsy. The otoneurological examination included grading the three branches of the facial nerve with the House-Brackman score, otomicroscopy and investigation with Frenzel glasses. A paediatrician interviewed the families. Medical files were analysed.

    Result: The incidence of complete recovery was 78% at the 2-year follow-up. In six out of 27 children (22%), the facial nerve function was mildly or moderately impaired. Four children reported problems with tear secretion and pronunciation. There was no correlation between sequelae after the facial palsy and gender, age, related symptoms, Lyme neuroborreliosis (NB), treatment, other health problems or performance.

    Conclusion: One fifth of children with an acute facial palsy get a permanent dysfunction of the facial nerve. Other neurological symptoms or health problems do not accompany the sequelae of the facial palsy. Lyme NB or treatment seems to have no correlation to clinical outcome. Factors of importance for complete recovery after an acute facial palsy are still not known.

    Keywords
    Facial palsy, Sequelae, Lyme borreliosis, Children
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13160 (URN)10.1016/S0165-5876(03)00061-2 (DOI)
    Available from: 2008-05-07 Created: 2008-05-07 Last updated: 2009-08-18
    2. Up-regulation of Borrelia-specific IL-4 and IFN-gamma secreting cells in cerebrospinal fluid from children with Lyme neuroborreliosis
    Open this publication in new window or tab >>Up-regulation of Borrelia-specific IL-4 and IFN-gamma secreting cells in cerebrospinal fluid from children with Lyme neuroborreliosis
    Show others...
    2005 (English)In: International Immunology, ISSN 0953-8178, Vol. 17, no 10, p. 1283-1291Article in journal (Refereed) Published
    Abstract [en]

    The clinical course and outcome of several infectious diseases are dependent on the type of immune response elicited against the pathogen. In adults with neuroborreliosis (NB), a type 1 response with high production of Borrelia-specific IFN-, but no IL-4, has been reported. Since children have a more benign course of NB than adults, we wanted to investigate type 1 and type 2 responses in children with NB. Cerebrospinal fluid (CSF) and blood were collected from children during the acute stage of ‘confirmed NB’ (n = 34), ‘possible NB’ (n = 30) and ‘non-NB’ (n = 10). The number of Borrelia-specific IL-4- and IFN--secreting cells was measured by enzyme-linked immunospot assay. Borrelia-specific secretion of both IL-4 and IFN- was increased in CSF in confirmed (P < 0.05) and possible (P < 0.01) NB, when compared with non-NB controls. Furthermore, children with NB had significantly higher Borrelia-specific IL-4 secretion in CSF than an adult reference material with NB (P < 0.05). There were no differences in cytokine secretion in relation to onset or recovery of neurological symptoms. Since IL-4 is known to down-regulate the pro-inflammatory and possibly harmful effects of prolonged IFN- responses, the prominent IL-4 response observed in the central nervous system compartment might contribute to the more benign disease course seen in children with Lyme NB.

    Keywords
    cytokines, IL-4, IFN-{gamma}, immune response, ELISPOT
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13161 (URN)10.1093/intimm/dxh304 (DOI)
    Available from: 2008-05-07 Created: 2008-05-07 Last updated: 2013-08-29
    3. Improved Laboratory Diagnostics of Lyme Neuroborreliosis in Children
    Open this publication in new window or tab >>Improved Laboratory Diagnostics of Lyme Neuroborreliosis in Children
    Show others...
    2008 (English)In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 27, no 7, p. 605-612Article in journal (Refereed) Published
    Abstract [en]

    Background: Laboratory diagnostics in Lyme neuroborreliosis need improvement. We hereby investigate 4 new recombinant or peptide Borrelia antigens in cerebrospinal fluid in children with neuroborreliosis to evaluate their performance as diagnostic antigens.

    Methods: An enzyme-linked immunosorbent assay was used to detect IgG antibodies to recombinant decorin binding protein A (DbpA), BBK32, outer surface protein C (OspC), and the invariable region 6 peptide (IR6). The recombinant antigens originated from 3 pathogenic subspecies; Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi sensu stricto. Cerebrospinal fluid and serum from children with clinical features indicative for neuroborreliosis (n = 57) were analyzed. Classification of patients was based on clinical symptoms and laboratory findings. Controls were children with other neurologic diseases (n = 20) and adult patients with no proven infection (n = 16).

    Results: Sensitivity for DbpA was 82%, for BBK32 70%, for OspC 58% and for IR6 70%. Specificities were 94%, 100%, 97%, and 97%, respectively. No single antigen was superior. When new antigens were combined in a panel, sensitivity was 80% and specificity 100%. The reference flagella antigen showed a sensitivity of 60% and a specificity of 100%. Over all, the B. garinii related antigens dominated.

    Conclusions: Recombinant DbpA and BBK32 as well as the peptide antigen IR6 perform well in laboratory diagnostics of neuroborreliosis in children. New antigens seem to improve diagnostic performance when compared with the routine flagella antigen. If different antigens are combined in a panel to cover the antigenic diversity, sensitivity improves further and a specificity of 100% can be achieve.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13162 (URN)10.1097/INF.0b013e31816a1e29 (DOI)
    Available from: 2008-05-07 Created: 2008-05-07 Last updated: 2017-12-13
    4. Lyme Neuroborreliosis in Children - a Prospective Study of Clinical features, Prognosis, and Outcome
    Open this publication in new window or tab >>Lyme Neuroborreliosis in Children - a Prospective Study of Clinical features, Prognosis, and Outcome
    Show others...
    2008 (English)In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 27, no 12, p. 1089-1094Article in journal (Refereed) Published
    Abstract [en]

     

    Background: Evaluation of children with clinically suspected neuroborreliosis (NB) is difficult. With a prospective study design we wanted to characterize children with signs and symptoms indicative for NB, investigate clinical outcome and, if possible, identify factors of importance for recovery.

    Material/Methods: Children being evaluated for NB (n = 177) in Southeast Sweden were categorized into 3 groups: "confirmed neuroborreliosis" (41%) with Borrelia antibodies in the cerebrospinal fluid, "possible neuroborreliosis" (26%) with pleocytosis but 110 Borrelia antibodies in the cerebrospinal fluid, and "not determined" (33%) with no pleocytosis and no Borrelia antibodies in the cerebrospinal fluid, Antibiotic treatment was given to 69% of children. Patients were followed during 6 months and compared with a matched control group (n = 174).

    Results: Clinical recovery at the 6-month follow-up (n = 177) was generally good and no patient was found to have recurrent or progressive neurologic symptoms. However, persistent facial nerve palsy caused dysfunctional and cosmetic problems in 11% of patients. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. Influence on daily life was reported to the same extent in patients and controls. Consequently, persistent headache and fatigue at follow-up should not be considered as attributable to NB. No prognostic factors could be identified.

    Conclusions: Clinical recovery was satisfactory in children being evaluated for NB although persistent symptoms from facial nerve palsy occurred. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls.

    Keywords
    Lyme disease, neuroborreliosis, children, clinical outcome, prognostic factors, prospective
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13163 (URN)10.1097/INF.0b013e31817fd423 (DOI)
    Available from: 2008-05-07 Created: 2008-05-07 Last updated: 2017-12-13
  • 2.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Croner, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Lahdenne, Pekka
    Hospital for Children and Adolescents, Helsinki University Central Hospital.
    Sillanpää, Heidi
    Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki.
    Seppälä, Ilkka
    Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki.
    Improved Laboratory Diagnostics of Lyme Neuroborreliosis in Children2008In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 27, no 7, p. 605-612Article in journal (Refereed)
    Abstract [en]

    Background: Laboratory diagnostics in Lyme neuroborreliosis need improvement. We hereby investigate 4 new recombinant or peptide Borrelia antigens in cerebrospinal fluid in children with neuroborreliosis to evaluate their performance as diagnostic antigens.

    Methods: An enzyme-linked immunosorbent assay was used to detect IgG antibodies to recombinant decorin binding protein A (DbpA), BBK32, outer surface protein C (OspC), and the invariable region 6 peptide (IR6). The recombinant antigens originated from 3 pathogenic subspecies; Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi sensu stricto. Cerebrospinal fluid and serum from children with clinical features indicative for neuroborreliosis (n = 57) were analyzed. Classification of patients was based on clinical symptoms and laboratory findings. Controls were children with other neurologic diseases (n = 20) and adult patients with no proven infection (n = 16).

    Results: Sensitivity for DbpA was 82%, for BBK32 70%, for OspC 58% and for IR6 70%. Specificities were 94%, 100%, 97%, and 97%, respectively. No single antigen was superior. When new antigens were combined in a panel, sensitivity was 80% and specificity 100%. The reference flagella antigen showed a sensitivity of 60% and a specificity of 100%. Over all, the B. garinii related antigens dominated.

    Conclusions: Recombinant DbpA and BBK32 as well as the peptide antigen IR6 perform well in laboratory diagnostics of neuroborreliosis in children. New antigens seem to improve diagnostic performance when compared with the routine flagella antigen. If different antigens are combined in a panel to cover the antigenic diversity, sensitivity improves further and a specificity of 100% can be achieve.

  • 3.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Croner, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nordwall, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
    Eknefelt, Mattias
    Pediatric Clinic, Jönköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Lyme Neuroborreliosis in Children - a Prospective Study of Clinical features, Prognosis, and Outcome2008In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 27, no 12, p. 1089-1094Article in journal (Refereed)
    Abstract [en]

     

    Background: Evaluation of children with clinically suspected neuroborreliosis (NB) is difficult. With a prospective study design we wanted to characterize children with signs and symptoms indicative for NB, investigate clinical outcome and, if possible, identify factors of importance for recovery.

    Material/Methods: Children being evaluated for NB (n = 177) in Southeast Sweden were categorized into 3 groups: "confirmed neuroborreliosis" (41%) with Borrelia antibodies in the cerebrospinal fluid, "possible neuroborreliosis" (26%) with pleocytosis but 110 Borrelia antibodies in the cerebrospinal fluid, and "not determined" (33%) with no pleocytosis and no Borrelia antibodies in the cerebrospinal fluid, Antibiotic treatment was given to 69% of children. Patients were followed during 6 months and compared with a matched control group (n = 174).

    Results: Clinical recovery at the 6-month follow-up (n = 177) was generally good and no patient was found to have recurrent or progressive neurologic symptoms. However, persistent facial nerve palsy caused dysfunctional and cosmetic problems in 11% of patients. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. Influence on daily life was reported to the same extent in patients and controls. Consequently, persistent headache and fatigue at follow-up should not be considered as attributable to NB. No prognostic factors could be identified.

    Conclusions: Clinical recovery was satisfactory in children being evaluated for NB although persistent symptoms from facial nerve palsy occurred. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls.

  • 4.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Croner, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ödkvist, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Acute facial palsy in children - a 2-year follow-up study with focus on Lyme neuroborreliosis2003In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, Vol. 67, no 6, p. 597-602Article in journal (Refereed)
    Abstract [en]

    Objective: Acute facial palsy in children is believed to be a rather benign neurological condition. Follow-up-studies are sparse, especially including a thorough otoneurological re-examination. The aim of this study was to examine children with a history of facial palsy in order to register the incidence of complete recovery and the severity and nature of sequelae. We also wanted to investigate whether there was a correlation between sequelae and Lyme Borreliosis, treatment or other health problems.

    Methods: Twenty-seven children with a history of facial palsy were included. A re-examination was performed by an Ear-Nose-Throat (ENT) specialist 1–2.9 years (median 2) after the acute facial palsy. The otoneurological examination included grading the three branches of the facial nerve with the House-Brackman score, otomicroscopy and investigation with Frenzel glasses. A paediatrician interviewed the families. Medical files were analysed.

    Result: The incidence of complete recovery was 78% at the 2-year follow-up. In six out of 27 children (22%), the facial nerve function was mildly or moderately impaired. Four children reported problems with tear secretion and pronunciation. There was no correlation between sequelae after the facial palsy and gender, age, related symptoms, Lyme neuroborreliosis (NB), treatment, other health problems or performance.

    Conclusion: One fifth of children with an acute facial palsy get a permanent dysfunction of the facial nerve. Other neurological symptoms or health problems do not accompany the sequelae of the facial palsy. Lyme NB or treatment seems to have no correlation to clinical outcome. Factors of importance for complete recovery after an acute facial palsy are still not known.

  • 5.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Croner, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Kampanj för TBE vaccination av små barn oetisk och felaktig2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 37, p. 2832-2832Article in journal (Other academic)
  • 6.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Croner, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    TBE-vaccinera barn över 7 år i endemiska områden, men låt de små barnen slippa.2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 43, p. 3367-3367Article in journal (Other (popular science, discussion, etc.))
  • 7.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Jarefors, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Hedin-Skogman, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Peterson, E. M.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Bergstrom, S.
    University of Umeå.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    T-Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis2009In: SCANDINAVIAN JOURNAL OF IMMUNOLOGY, ISSN 0300-9475, Vol. 70, no 2, p. 141-148Article in journal (Refereed)
    Abstract [en]

    We studied the T-cell reactivity to overlapping peptides of B. garinii OspA, in order to locate possible immunodominant T-cell epitopes in neuroborreliosis. Cells from cerebrospinal fluid (CSF) and blood from 39 patients with neuroborreliosis and 31 controls were stimulated with 31 overlapping peptides, and interferon-gamma secreting cells were detected by ELISPOT. The peptides OspA(17-36), OspA(49-68), OspA(105-124), OspA(137-156), OspA(193-212) and OspA(233-252) showed the highest frequency of positive responses, being positive in CSF from 38% to 50% of patients with neuroborreliosis. These peptides also elicited higher responses in CSF compared with controls (P = 0.004). CSF cells more often showed positive responses to these peptides than blood cells (P = 0.001), in line with a compartmentalization to the central nervous system. Thus, a set of potential T-cell epitopes were identified in CSF cells from patients with neuroborreliosis. Further studies may reveal whether these epitopes can be used diagnostically and studies involving HLA interactions may show their possible pathogenetic importance.

  • 8.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Hedin Skogman, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Bergström, Sven
    Department of Microbiology, University of Umeå, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Jarefors, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Eknefelt, Mattias
    Pediatric Clinic, Ryhov County Hospital, Jönköping, Sweden.
    Eneström, Gunilla
    Pediatric Clinic, Västervik Hospital, Västervik, Sweden.
    Nordwall, Maria
    Pediatric Clinic, Vrinnevi Hospital, Norrköping, Sweden.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Croner, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Up-regulation of Borrelia-specific IL-4 and IFN-gamma secreting cells in cerebrospinal fluid from children with Lyme neuroborreliosis2005In: International Immunology, ISSN 0953-8178, Vol. 17, no 10, p. 1283-1291Article in journal (Refereed)
    Abstract [en]

    The clinical course and outcome of several infectious diseases are dependent on the type of immune response elicited against the pathogen. In adults with neuroborreliosis (NB), a type 1 response with high production of Borrelia-specific IFN-, but no IL-4, has been reported. Since children have a more benign course of NB than adults, we wanted to investigate type 1 and type 2 responses in children with NB. Cerebrospinal fluid (CSF) and blood were collected from children during the acute stage of ‘confirmed NB’ (n = 34), ‘possible NB’ (n = 30) and ‘non-NB’ (n = 10). The number of Borrelia-specific IL-4- and IFN--secreting cells was measured by enzyme-linked immunospot assay. Borrelia-specific secretion of both IL-4 and IFN- was increased in CSF in confirmed (P < 0.05) and possible (P < 0.01) NB, when compared with non-NB controls. Furthermore, children with NB had significantly higher Borrelia-specific IL-4 secretion in CSF than an adult reference material with NB (P < 0.05). There were no differences in cytokine secretion in relation to onset or recovery of neurological symptoms. Since IL-4 is known to down-regulate the pro-inflammatory and possibly harmful effects of prolonged IFN- responses, the prominent IL-4 response observed in the central nervous system compartment might contribute to the more benign disease course seen in children with Lyme NB.

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