To investigate whether persons with treatment-resistant
Lyme arthritis-associated HLA alleles might develop arthritis as a result of an autoimmune reaction triggered by Borrelia burgdorferi outer surface protein A (OspA), the
Lyme disease vaccine antigen.
Persons in whom inflammatory arthritis had developed after
Lyme disease vaccine (cases) were compared with 3 control groups: 1) inflammatory arthritis but not
Lyme disease vaccine (arthritis controls), 2)
Lyme disease vaccine but not inflammatory arthritis (vaccine controls), and 3) neither
Lyme disease vaccine nor inflammatory arthritis (normal controls). HLA-DRB1 allele typing, Western blotting for
Lyme antigen, and T cell reactivity testing were performed.
Twenty-seven cases were matched with 162 controls (54 in each control group). Odds ratios (ORs) for the presence of 1 or 2 treatment-resistant
Lyme arthritis alleles were 0.8 (95% confidence interval [95% CI] 0.3-2.1), 1.6 (95% CI 0.5-4.4), and 1.75 (95% CI 0.6-5.3) in cases versus arthritis controls, vaccine controls, and normal controls, respectively. There were no significant differences in the frequency of DRB1 alleles. T cell response to OspA was similar between cases and vaccine controls, as measured using the stimulation index (OR 1.6 [95% CI 0.5-5.1]) or change in uptake of tritiated thymidine (counts per minute) (OR 0.7 [95% CI 0.2-2.3]), but cases were less likely to have IgG antibodies to OspA (OR 0.3 [95% CI 0.1-0.8]). Cases were sampled closer to the time of vaccination (median 3.59 years versus 5.48 years), and fewer cases had received 3 doses of vaccine (37% versus 93%).
Lyme arthritis alleles were not found more commonly in persons who developed arthritis after
Lyme disease vaccination, and immune responses to OspA were not significantly more common in arthritis cases. These results suggest that
Lyme disease vaccine is not a major factor in the development of arthritis in these cases.