Treg cell numbers and function in patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis.

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.

• Authors: Shiqian Shen, Junghee J Shin, Klemen Strle, Gail McHugh, Xin Li, Lisa J Glickstein, Elise E Drouin, Allen C Steere
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 62 Issue 7 Pg. 2127-37 (Jul 2010) ISSN: 1529-0131 [Electronic] United States
• PMID: 20506317 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents

Topics

• Adolescent
• Adult
• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Arthritis, Infectious (drug therapy, immunology, pathology)
• Borrelia burgdorferi (drug effects)
• CD4 Lymphocyte Count
• Cell Proliferation
• Child
• Drug Resistance, Bacterial (drug effects)
• Female
• Humans
• Lyme Disease (drug therapy, immunology, pathology)
• Lymphocyte Activation
• Male
• Middle Aged
• Synovial Fluid (cytology, immunology)
• T-Lymphocyte Subsets (immunology, pathology)
• T-Lymphocytes, Regulatory (immunology, pathology)
• Young Adult