title: T-Helper 17 Cell Cytokine Responses in Lyme Disease Correlate With Borrelia burgdorferi Antibodies During Early Infection and With Autoantibodies Late in the Illness in Patients With Antibiotic-Refractory Lyme Arthritis.
abstract: BACKGROUND
  Control of Lyme disease is attributed predominantly to innate and adaptive T-helper 1 cell (TH1) immune responses, whereas the role of T-helper 17 cell (TH17) responses is less clear. Here we characterized these inflammatory responses in patients with erythema migrans (EM) or Lyme arthritis (LA) to elucidate their role early and late in the infection.
  
  
  METHODS
  Levels of 21 cytokines and chemokines, representative of innate, TH1, and TH17 immune responses, were assessed by Luminex in acute and convalescent sera from 91 EM patients, in serum and synovial fluid from 141 LA patients, and in serum from 57 healthy subjects. Antibodies to Borrelia burgdorferi or autoantigens were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Compared with healthy subjects, EM patients had significantly higher levels of innate, TH1, and TH17-associated mediators (P ≤ .05) in serum. In these patients, the levels of inflammatory mediators, particularly TH17-associated cytokines, correlated directly with B. burgdorferi immunoglobulin G antibodies (P ≤ .02), suggesting a beneficial role for these responses in control of early infection. Late in the disease, in patients with LA, innate and TH1-associated mediators were often >10-fold higher in synovial fluid than serum. In contrast, the levels of TH17-associated mediators were more variable, but correlated strongly with autoantibodies to endothelial cell growth factor, matrix metalloproteinase 10, and apolipoprotein B-100 in joints of patients with antibiotic-refractory LA, implying a shift in TH17 responses toward an autoimmune phenotype.
  
  
  CONCLUSIONS
  Patients with Lyme disease often develop pronounced TH17 immune responses that may help control early infection. However, late in the disease, excessive TH17 responses may be disadvantageous by contributing to autoimmune responses associated with antibiotic-refractory LA.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, and.
authors.forename: Klemen
authors.initials: K
authors.lastname: Strle
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, and.
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Sulka
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, and.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pianta
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, and.
authors.forename: Jameson T
authors.initials: JT
authors.lastname: Crowley
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, and.
authors.forename: Sheila L
authors.initials: SL
authors.lastname: Arvikar
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Anthony
authors.initials: A
authors.lastname: Anselmo
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Sadreyev
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, and.
authors.forename: Allen C
authors.initials: AC
authors.lastname: Steere
mesh_terms: D056704:Adaptive Immunity; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D001168:Arthritis / Q000209:etiology / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D015415:Biomarkers; D025065:Borrelia burgdorferi / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005260:Female; D005929:Glossitis, Benign Migratory / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D008193:Lyme Disease / Q000150:complications / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D000907:Antibodies, Bacterial; D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators
keywords: Lyme arthritis; Lyme disease; TH17; antibodies; erythema migrans