Author/Editor     Shen, Shiqian; Shin, Junghee J; Strle, Klemen; McHugh, Gail; Li, Xin; Glickstein, Lisa J; Drouin, Elise E; Steere, Allen C
Title     Treg cell numbers and function in patients with antibiotic-refractory or antibiotic-responsive lyme arthritis
Type     članek
Source     Arthritis Rheum
Vol. and No.     Letnik 62, št. 7
Publication year     2010
Volume     str. 2127-37
Language     eng
Abstract     Objective: In a murine model of antibiotic-refractory Lyme arthritis, the numbers of Treg cells are dramatically reduced. The aim of this study was to examine Treg cell numbers and function in patients with antibiotic-refractory Lyme arthritis. Methods: CD4+ T cell subsets were enumerated in the peripheral blood (PB) and synovial fluid (SF) of 12 patients with antibiotic-refractory arthritis and 6 patients with antibiotic-responsive arthritis. Treg cell function was examined using Borrelia-specific and nonspecific Treg cell proliferation assays. Results: In both patient groups, interferon-gamma-positive Th1 cells in SF were abundant and enriched ( approximately 50% of CD4+ T cells). In patients with antibiotic-refractory arthritis, the median percentages of FoxP3-positive Treg cells were significantly higher in SF than in PB (12% versus 6%; P = 0.03) or in SF from patients with antibiotic-responsive arthritis (12% versus 5%; P = 0.04). Moreover, in the antibiotic-refractory group, a higher percentage of Treg cells in SF correlated with a shorter duration until resolution of arthritis (r = -0.74, P = 0.006). In contrast, patients with fewer Treg cells had suboptimal responses to disease-modifying antirheumatic drugs and a longer duration of arthritis after antibiotic treatment, and they often required synovectomies for arthritis resolution. In each group, Treg cells in SF dampened Borrelia burgdorferi-specific proliferative responses, and in 2 patients with antibiotic-refractory arthritis, Treg cells were functional in nonspecific suppression assays. Conclusion: Treg cells were functional in patients with antibiotic-refractory arthritis, and in some patients, higher numbers of these cells in SF appeared to participate in arthritis resolution. However, as in the murine model, patients with antibiotic-refractory arthritis and lower numbers of Treg cells seemed unable to achieve resolution of synovial inflammation.
Descriptors     LYME DISEASE
ARTHRITIS
ANTIBIOTICS
DRUG RESISTANCE, MICROBIAL
CD4-POSITIVE T-LYMPHOCYTES
SYNOVIAL FLUID
BORRELIA BURGDORFERI
TH1 CELLS
MONOCYTES
POLYMERASE CHAIN REACTION