Ab response to B. burgdorferi (whole-cell lysate), full-length VlsE, and individual VlsE epitopes. Mean levels of IgG reactivity to B. burgdorferi (whole-cell lysate) (A), IgG to full-length recombinant VlsE protein (B), IgG to VlsE274 (C), C6 Ab (D), IgG to VlsE21 (E), and IgG to VlsE336 (F), as measured by ELISA, in healthy controls (HC) (n = 30) and in patients with single EM (n = 18), multiple EM (n = 17), early neurologic (n = 16), late neurologic (n = 16), antibiotic-responsive arthritis (n = 12), and antibiotic-refractory arthritis (n = 11) manifestations of Lyme disease. Error bars represent the SEM. Levels of statistical significance for differences in Ab reactivity are as follows. (A) Healthy versus multiple EM, early neurologic, late neurologic, responsive arthritis, and refractory arthritis: p < 0.001, p < 0.0001, p < 0.0001, p < 0.0001, and p < 0.0001, respectively; single EM versus early neurologic, late neurologic, responsive arthritis, and refractory arthritis: p < 0.01, p < 0.01, p < 0.0001, and p < 0.0001, respectively. (B) Healthy versus single EM, multiple EM, early neurologic, late neurologic, responsive arthritis, and refractory arthritis: p < 0.01, p < 0.001, p < 0.0001, p < 0.0001, p < 0.0001, and p < 0.0001, respectively; single EM versus early neurologic, late neurologic, responsive arthritis, and refractory arthritis: p < 0.01 for each comparison. (C and D) Healthy versus individual Lyme disease subgroups: p < 0.0001 for each; single EM versus other Lyme disease subgroups: p < 0.05 for each. (E) Healthy versus late neurologic, responsive arthritis, and refractory arthritis: p < 0.01, p < 0.0001, and p < 0.0001, respectively; single EM versus late neurologic, responsive arthritis, and refractory arthritis: p < 0.01, p < 0.0001, and p < 0.0001; multiple EM versus late neurologic, responsive arthritis, and refractory arthritis: p < 0.01, p < 0.0001, and p < 0.0001, respectively; early neurologic versus late neurologic, responsive arthritis, and refractory arthritis: p < 0.05, p < 0.001, and p < 0.0001, respectively. (F) Healthy versus late neurologic, responsive arthritis, and refractory arthritis: p < 0.01, p < 0.001, and p < 0.0001, respectively; single EM versus late neurologic, responsive arthritis, and refractory arthritis: p < 0.05, p < 0.01, and p < 0.001; multiple EM versus late neurologic, responsive arthritis, and refractory arthritis: p < 0.05, p < 0.01, and p < 0.001, respectively; early neurologic versus responsive arthritis and refractory arthritis: p < 0.05 and p < 0.01, respectively. Differences for other group comparisons were not statistically significant.