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



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.



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.



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.
Department of Infectious Diseases, Region Jönköping County, SE-551 85, Jönköping, Sweden. paula.gyllemark@rjl.se.
Paula
0000-0002-4915-564X
P
Gyllemark
Department of Clinical and Experimental Medicine and Department of Infectious Diseases, Linköping University, Linköping, Sweden.
Pia
P
Forsberg
Department of Clinical and Experimental Medicine and Department of Clinical Immunology and Transfusion Medicine, Linköping University, Linköping, Sweden.
Jan
J
Ernerudh
Clinical Microbiology, Division of Medical Services, Jönköping, Region Jönköping County, Sweden.
Anna J
AJ
Henningsson
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D018925:Chemokines / Q000134:cerebrospinal fluid* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016207:Cytokines / Q000134:cerebrospinal fluid* / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D020852:Lyme Neuroborreliosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013129:Spinal Puncture; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines
APRIL; BAFF; CCL20; CXCL 1; CXCL13; Cerebrospinal fluid; Chemokines; Cytokines; IL-17A; Lyme neuroborreliosis