The Lyme Disease Network
Medical / Scientific Abstract


Title:Association of antibiotic treatment-resistant Lyme arthritis with T cell responses to dominant epitopes of outer surface protein A of Borrelia burgdorferi [see comments]
Authors:Chen J, Field JA, Glickstein L, Molloy PJ, Huber BT, Steere AC
Source:Arthritis Rheum 1999 Sep;42(9):1813-22
Organization:Tufts University School of Medicine, Boston, Massachusetts, USA.

Abstract:
OBJECTIVE: To explore further the association of antibiotic treatment-resistant Lyme arthritis and T cell reactivity with outer surface protein A (OspA) of Borrelia burgdorferi, including the identification of T cell epitopes associated with this treatment-resistant course. METHODS: The responses of peripheral blood and, if available, synovial fluid lymphocytes to B burgdorferi proteins, fragments, and synthetic peptides, as determined by proliferation assay and interferon-gamma production, were compared in 16 patients with treatment-responsive and 16 with treatment-resistant Lyme arthritis. RESULTS: The maximum severity of joint swelling correlated directly with the response to OspA. Moreover, the only significant difference between patients with treatment-resistant and treatment-responsive arthritis was in reactivity with N-terminal and C-terminal fragments of OspA, OspA1 (amino acids [aa] 16-106), and OspA3 (aa 168-273). Epitope mapping showed that 14 of the 16 patients with treatment-resistant arthritis had responses to OspA peptides (usually 4 or 5 epitopes), whereas only 5 of the 16 patients with treatment-responsive arthritis had reactivity with these peptides (usually 1 or 2 epitopes) (P = 0.003). Patients with HLA-DRB1 alleles associated with treatment-resistant arthritis were more likely to react with peptide 15 (aa 154-173) and, to a lesser degree, with peptide 21 (aa 214-233) than patients with other alleles, whereas the responses to other epitopes were similar in both groups. CONCLUSION: The maximum severity of joint swelling and the duration of Lyme arthritis after antibiotic treatment are associated with T cell responses to specific epitopes of OspA.

Keywords:
Adolescence, Adult, Aged, Alleles, Antibiotics, Tetracycline, THERAPEUTIC USE, Antibody Formation, Antigens, Surface, IMMUNOLOGY, Bacterial Outer Membrane Proteins, IMMUNOLOGY, Bacterial Vaccines, IMMUNOLOGY, Borrelia burgdorferi, Child, Doxycycline, THERAPEUTIC USE, Drug Resistance, Microbial, IMMUNOLOGY, Epitope Mapping, Epitopes, T-Lymphocyte, DRUG EFFECTS, Female, Human, HLA Antigens, GENETICS, Immunodominant Epitopes, IMMUNOLOGY, Lyme Disease, DRUG THERAPY, IMMUNOLOGY, Male, Middle Age, Severity of Illness Index, Support, Non-U.S. Gov't, Support, U.S. Gov't, P.H.S., T-Lymphocytes, IMMUNOLOGY, Tetracycline Resistance, IMMUNOLOGY, Time Factors

Language: Eng

Unique ID: 99441952


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