Session Type: Abstract Submissions (ACR)
Lyme disease usually begins with an expanding skin lesion, erythema migrans (EM), whereas arthritis is a late disease manifestation. The infection usually resolves with appropriate antibiotic therapy, but post-infectious symptoms following EM or persistent synovitis despite antibiotic therapy (antibiotic-refractory arthritis) may occur. Control of the infection in humans is attributed predominantly to innate and adaptive TH1 immune responses, whereas the role of TH17 responses is not yet well characterized. We recently showed that high levels of IL-23, a TH17-associated cytokine, occur in a subset of European patients with EM, and are associated with more frequent post-infectious symptoms and autoantibody responses. Here, we characterized these responses in a large cohort of American patients with EM or Lyme arthritis to elucidate the role of TH17-mediated immunity throughout the infection.
The levels of 20 cytokines and chemokines, representative of innate and adaptive TH1 and TH17 immune responses, were assessed by Luminex in matched acute and convalescent serum samples from 106 culture-positive patients with EM, in matched serum and synovial fluid (SF) samples from 159 patients with antibiotic-responsive or antibiotic-refractory arthritis, and in serum samples from 57 healthy control subjects.
Compared with healthy subjects, acute-phase sera from EM patients contained significantly higher levels of the TH17-associated mediators (IL-6, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25 and IL-27; P≤0.01). With the exception of IL-27, which down-regulates TH17 responses, the levels of other TH17-associated mediators remained elevated in convalescent sera obtained at the conclusion of antibiotic therapy. The levels of IL-23, the most highly induced TH17 cytokine, correlated directly with antibody levels to the B. burgdorferi VlsE antigen (P=0.04) in both acute and convalescent samples, suggesting a role for TH17-associated mediators in control of the infection. In patients with Lyme arthritis, the serum levels of IL-23 and other TH17-associated mediators were generally lower than in patients with EM, and the levels of these mediators were only minimally concentrated, if at all, in SF. In contrast, innate (IL-8) and TH1 mediators (CXCL9 and CXCL10) were >50-fold higher in SF than in serum. Compared with antibiotic-responsive patients, there was a trend toward higher levels of most of the TH17-associated mediators, particularly IL-23, in SF in patients with antibiotic-refractory arthritis, and toward a greater frequency of autoantibody responses to human endothelial cell growth factor, the first known target of T and B cell responses in this disease.
A subset of patients with Lyme disease develops TH17 immune responses. TH17-associated mediators seem to be highest early in the infection and may play a role in control of the infection. In addition, TH17 mediators may be one factor in shaping an immune response early in the illness in which autoantibody responses are more common, thereby contributing to subsequent antibiotic refractory Lyme arthritis.
NIH, Arthritis Foundation,
E. E. Drouin,
A. C. Steere,
ACR, NIH, Foundation,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/th17-inflammatory-responses-occur-in-a-subset-of-patients-with-erythema-migrans-or-lyme-arthritis-but-are-not-predominant-responses-in-joints/