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Decline in the Frequencies of Borrelia burgdorferi OspA_161–175-Specific T Cells after Antibiotic Therapy in HLA-DRB1*0401-Positive Patients with Antibiotic-Responsive or Antibiotic-Refractory Lyme Arthritis¹

Priya Kannian^*, Elise E. Drouin^*, Lisa Glickstein^*, William W. Kwok, Gerald T. Nepom and Allen C. Steere^2,*

^* Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; and Benaroya Research Institute, Virginia Mason Medical Center, University of Washington, Seattle, WA 98101

Synovitis in patients with antibiotic-refractory Lyme arthritis persists for months to several years after antibiotic therapy. This course, which may result from infection-induced autoimmunity, is associated with T cell recognition of Borrelia burgdorferi outer surface protein A (OspA_161–175) and with HLA-DR molecules that bind this epitope, including the DRB1*0401 molecule. In this study, we used tetramer reagents to determine the frequencies of OspA_161–175-specific T cells in samples of PBMC and synovial fluid mononuclear cells (SFMC) from 13 DRB1*0401-positive patients with antibiotic-responsive or antibiotic-refractory arthritis. Initially, three of the six patients (50%) with antibiotic-responsive arthritis and four of the seven patients (57%) with antibiotic-refractory arthritis had frequencies of OspA_161–175-specific CD4⁺ T cells in peripheral blood above the cutoff value of 4 per 10⁵ cells. Among the five patients with concomitant PBMC and SFMC, four (80%) had OspA tetramer-positive cells at both sites, but the mean frequency of such cells was 16 times higher in SFMC, reaching levels as high as 1,177 per 10⁵ cells. In the two patients in each patient group in whom serial samples were available, the frequencies of OspA_161–175-specific T cells declined to low or undetectable levels during or soon after antibiotic therapy, months before the resolution of synovitis in the two patients with antibiotic-refractory arthritis. Thus, the majority of patients with Lyme arthritis initially have increased frequencies of OspA_161–175-specific T cells. However, the marked decline in the frequency of such cells with antibiotic therapy suggests that persistent synovitis in the refractory group is not perpetuated by these cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institutes of Health Grant AR-20358 and by the English-Bonter-Mitchell Foundation, the Eshe Fund, and the Lyme/Arthritis Research Fund at Massachusetts General Hospital, Boston, MA. P. K. received a scholarship for the study of Lyme disease from the Lillian B. Davey Foundation.

² Address correspondence and reprint requests to Dr. Allen C. Steere, MD, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 55 Fruit Street, Charlestown Navy Yard 149/8301, Boston, MA 02114. E-mail address: asteere{at}partners.org

³ Abbreviations used in this paper: OspA, outer surface protein A; HA, hemagglutinin; SFMC, synovial fluid mononuclear cell.