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1. Intrathecal Th17- and B cell-associated cytokine and chemokine responses in relation to clinical outcome in Lyme neuroborreliosis: a large retrospective study.

Author

Gyllemark, Paula, Forsberg, Pia, Ernerudh, Jan, and Henningsson, Anna J.

Subjects
*B cells, *CYTOKINES, *CHEMOKINES, *RELAPSING fever, *CEREBROSPINAL fluid, *BIOMARKERS, *LYME disease diagnosis, *LYMPHOCYTE metabolism, *LONGITUDINAL method, *LYME neuroborreliosis, *LYMPHOCYTES, *LUMBAR puncture, *TREATMENT effectiveness, *RETROSPECTIVE studies, *DIAGNOSIS, CENTRAL nervous system infections
Abstract

Background: B cell immunity, including the chemokine CXCL13, has an established role in Lyme neuroborreliosis, and also, T helper (Th) 17 immunity, including IL-17A, has recently been implicated.Methods: We analysed a set of cytokines and chemokines associated with B cell and Th17 immunity in cerebrospinal fluid and serum from clinically well-characterized patients with definite Lyme neuroborreliosis (group 1, n = 49), defined by both cerebrospinal fluid pleocytosis and Borrelia-specific antibodies in cerebrospinal fluid and from two groups with possible Lyme neuroborreliosis, showing either pleocytosis (group 2, n = 14) or Borrelia-specific antibodies in cerebrospinal fluid (group 3, n = 14). A non-Lyme neuroborreliosis reference group consisted of 88 patients lacking pleocytosis and Borrelia-specific antibodies in serum and cerebrospinal fluid.Results: Cerebrospinal fluid levels of B cell-associated markers (CXCL13, APRIL and BAFF) were significantly elevated in groups 1, 2 and 3 compared with the reference group, except for BAFF, which was not elevated in group 3. Regarding Th17-associated markers (IL-17A, CXCL1 and CCL20), CCL20 in cerebrospinal fluid was significantly elevated in groups 1, 2 and 3 compared with the reference group, while IL-17A and CXCL1 were elevated in group 1. Patients with time of recovery <3 months had lower cerebrospinal fluid levels of IL-17A, APRIL and BAFF compared to patients with recovery >3 months.Conclusions: By using a set of markers in addition to CXCL13 and IL-17A, we confirm that B cell- and Th17-associated immune responses are involved in Lyme neuroborreliosis pathogenesis with different patterns in subgroups. Furthermore, IL-17A, APRIL and BAFF may be associated with time to recovery after treatment. [ABSTRACT FROM AUTHOR]

Published
2017
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2. Intrathecal Th17- and B cell-associated cytokine and chemokine responses in relation to clinical outcome in Lyme neuroborreliosis : a large retrospective study

Author

Anna J. Henningsson, Jan Ernerudh, Paula Gyllemark, and Pia Forsberg

Subjects
Male, 0301 basic medicine, Lyme neuroborreliosis, Infektionsmedicin, Spinal Puncture, Cohort Studies, 0302 clinical medicine, Cerebrospinal fluid, IL-17A, APRIL, CXCL 1, Child, Aged, 80 and over, B-Lymphocytes, biology, General Neuroscience, CXCL13, Middle Aged, Treatment Outcome, medicine.anatomical_structure, Neurology, Child, Preschool, Cytokines, BAFF, Female, Chemokines, Antibody, Neuroborreliosis, Adult, Infectious Medicine, Adolescent, Immunology, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, medicine, Humans, Pleocytosis, B-cell activating factor, B cell, Aged, Retrospective Studies, business.industry, Research, Infant, medicine.disease, 030104 developmental biology, Lyme Neuroborreliosis, biology.protein, Th17 Cells, CCL20, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

BACKGROUND: B cell immunity, including the chemokine CXCL13, has an established role in Lyme neuroborreliosis, and also, T helper (Th) 17 immunity, including IL-17A, has recently been implicated. METHODS: We analysed a set of cytokines and chemokines associated with B cell and Th17 immunity in cerebrospinal fluid and serum from clinically well-characterized patients with definite Lyme neuroborreliosis (group 1, n = 49), defined by both cerebrospinal fluid pleocytosis and Borrelia-specific antibodies in cerebrospinal fluid and from two groups with possible Lyme neuroborreliosis, showing either pleocytosis (group 2, n = 14) or Borrelia-specific antibodies in cerebrospinal fluid (group 3, n = 14). A non-Lyme neuroborreliosis reference group consisted of 88 patients lacking pleocytosis and Borrelia-specific antibodies in serum and cerebrospinal fluid. RESULTS: Cerebrospinal fluid levels of B cell-associated markers (CXCL13, APRIL and BAFF) were significantly elevated in groups 1, 2 and 3 compared with the reference group, except for BAFF, which was not elevated in group 3. Regarding Th17-associated markers (IL-17A, CXCL1 and CCL20), CCL20 in cerebrospinal fluid was significantly elevated in groups 1, 2 and 3 compared with the reference group, while IL-17A and CXCL1 were elevated in group 1. Patients with time of recovery 3 months. CONCLUSIONS: By using a set of markers in addition to CXCL13 and IL-17A, we confirm that B cell- and Th17-associated immune responses are involved in Lyme neuroborreliosis pathogenesis with different patterns in subgroups. Furthermore, IL-17A, APRIL and BAFF may be associated with time to recovery after treatment. Funding agencies: Medical Research Council of Southeast Sweden (FORSS); Futurum-the Academy for Health and Care; Division of Medical Services, Region Jonkoping County; EU-Interreg project ScandTick Innovation

Published
2017

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