Correlation of the relative binding affinity of the Borrelia burgdorferi outer-surface protein A (OspA)_163–175 peptide for 14 HLA-DR molecules and percentage allele frequencies of these HLA-DR molecules in patients with antibiotic-refractory Lyme arthritis (antibiotic-refractory patients) or antibiotic-responsive Lyme arthritis (antibiotic-responsive patients). Seven of the 14 DRB molecules, which showed strong-to-weak binding of OspA_163–175, were more common among patients with antibiotic-refractory arthritis, whereas the other 7 DRB molecules, which showed negligible or no binding of the peptide, were more common among patients with antibiotic-responsive arthritis. Reproduced with permission from Steere et al [16].

Correlation of the duration of joint inflammation and the frequency of Borrelia burgdorferi outer-surface protein A (OspA)_161–175–specific T cells in peripheral blood in serial samples from 4 patients with antibiotic-responsive Lyme arthritis (antibiotic-responsive patients) or antibiotic-refractory Lyme arthritis (antibiotic-refractory patients). The 2 patients with antibiotic-responsive arthritis were first evaluated prior to antibiotic therapy, and both responded to a 1-month course of oral doxycycline. The 2 patients with antibiotic-refractory arthritis were first seen 1 and 4 months after the start of antibiotic therapy. Patient 3 (Pt#3) was treated with a 2-month course of oral doxycycline and a 1-month course of intravenous ceftriaxone. Patient 4 (Pt#4) received a 1-month course of doxycycline, followed 3 months later by a 1-month course of intravenous ceftriaxone. The cross-hatched areas show the amount of joint swelling, and the lines with closed circles show the frequency of OspA_161–175-specific T cells. In both patients with antibiotic-responsive arthritis and those with antibiotic-refractory arthritis, the frequencies of OspA_161–175-specific T cells decreased during the period of antibiotic therapy, whereas joint inflammation persisted for months longer in patients with antibiotic-refractory arthritis than in patients with antibiotic-responsive arthritis. Reproduced with permission from Kannian et al [20].

Serial assessment of immunoglobulin (Ig) G antibody titers to the Borrelia burgdorferi, VlsE C6 peptide and outer-surface protein A (OspA) protein in patients with antibiotic-responsive or antibiotic-refractory Lyme arthritis. The horizontal bars represent the median value in each group. The top of the hatched horizontal bars represents the cutoff value for a positive response; the bottom of the hatched horizontal bars represents the minimal dilution tested. The antibody response to the VlsE C6 peptide and to 2 other outer-surface proteins tested (data not shown) decreased similarly in both patient groups. In contrast, OspA antibody titers tended to be higher in the first 1–6 months after the start of antibiotic therapy in the antibiotic-refractory arthritis group but then decreased to similar levels in both patient groups. Mos, months. Reproduced with permission from Kannian et al [21].

T cell reactivity with 3 self-peptides or the Borrelia burgdorferi outer-surface protein A (OspA)_161–175 peptide in each of 11 patients with antibiotic-refractory Lyme arthritis. Among 11 patients, 9 had T cell–proliferative responses to the OspA peptide, 6 had reactivity with the MAP kinase activator with WD-repeats (MAWD-BP) peptide, 3 had responses to the T-span peptide, and 2 had reactivity with the LFA-1 peptide. However, reactivity with the self-peptides was less than that with the spirochetal peptide. Reproduced with permission from Drouin et al [17].

Interferon (IFN) γ production from lymph node cells and Borrelia burgdorferi outer-surface protein A (OspA) antibody titers in OspA-vaccinated mice with the DR4 or DR11 transgene lacking the CD28 co-receptor. DR11-tg and DR4-tg mice (15 mice per group) were vaccinated in the footpad (50 μg per mouse) with recombinant OspA (rOspA) in Freund's complete adjuvant. A, production of IFN-γ after in vitro restimulation of popliteal lymph node cells with rOspA (10 μg/mL) was assessed by enzyme-linked immunosorbent assay (ELISA). B, anti-OspA antibody titers were measured by ELISA 2 weeks after OspA vaccination. In both panels, mean values (± standard error of the mean) are given and include the results of 4 or 5 independent experiments. For the comparison in panel A, P = .003. For the comparison in panel B, P = .005. Reproduced with permission from Iliopoulou et al [29].