title: HLA type and immune response to Borrelia burgdorferi outer surface protein a in people in whom arthritis developed after Lyme disease vaccination.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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%).
  
  
  CONCLUSIONS
  Treatment-resistant 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.
authors.affiliation: Center for Biologics Evaluation and Research, FDA, Rockville, Maryland, USA. Robert.Ball@fda.hhs.gov
authors.forename: Robert
authors.initials: R
authors.lastname: Ball
authors.forename: Sean V
authors.initials: SV
authors.lastname: Shadomy
authors.forename: Abbie
authors.initials: A
authors.lastname: Meyer
authors.forename: Brigitte T
authors.initials: BT
authors.lastname: Huber
authors.forename: Mary S
authors.initials: MS
authors.lastname: Leffell
authors.forename: Andrea
authors.initials: A
authors.lastname: Zachary
authors.forename: Michael
authors.initials: M
authors.lastname: Belotto
authors.forename: Eileen
authors.initials: E
authors.lastname: Hilton
authors.forename: Marthe
authors.initials: M
authors.lastname: Bryant-Genevier
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schriefer
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Miller
authors.forename: M Miles
authors.initials: MM
authors.lastname: Braun