Association of antibiotic treatment-resistant lyme arthritis with T cell responses to dominant epitopes of outer surface protein A of Borrelia burgdorferi
J. Chen et al., Association of antibiotic treatment-resistant lyme arthritis with T cell responses to dominant epitopes of outer surface protein A of Borrelia burgdorferi, ARTH RHEUM, 42(9), 1999, pp. 1813-1822
Objective. To explore further the association of antibiotic treatment-resis
tant Lyme arthritis and T cell reactivity with outer surface protein A (Osp
A) 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 flui
d 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-re
sistant Lyme arthritis.
Results. The maximum severity of joint swelling correlated directly with th
e response to OspA. Moreover, the only significant difference between patie
nts with treatment-resistant and treatment-responsive arthritis was in reac
tivity 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 th
e 16 patients with treatment-resistant arthritis had responses to OspA pept
ides (usually 4 or 5 epitopes), whereas only 5 of the 16 patients with trea
tment-responsive arthritis had reactivity with these peptides (usually 1 or
2 epitopes) (P = 0.003). Patients with HLA-DRB1 alleles associated with tr
eatment-resistant arthritis were more likely to react with peptide 15 (aa 1
54-173) and, to a lesser degree, with peptide 21 (aa 214-233) than patients
with other alleles, whereas the responses to other epitopes were similar i
n 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.