Reduced IgG titers against pertussis in rheumatoid arthritis: Evidence for a citrulline-biased immune response and medication effects

BACKGROUND: The antibody response to pertussis vaccination in rheumatoid arthritis is unknown, a concerning omission given the relatively low efficacy of the pertussis vaccine, a rise in pertussis infections, and a general increased susceptibility to infection in rheumatoid arthritis. Additionally, the contributions from an intrinsically dysregulated immune system in rheumatoid arthritis and immune-suppressing medications to the response to pertussis vaccination is poorly defined. This study examines antibody titers against pertussis in vaccinated rheumatoid arthritis patients and controls as well as evaluates potential contributions from demographic factors, immune suppressing medications, and reactivity against citrullinated pertussis. METHODS: Serum IgG titers against native and citrullinated pertussis and tetanus were quantified by enzyme-linked immunosorbent assay in rheumatoid arthritis subjects and controls who were vaccinated within 10 years. Titers were compared by t-test and percent immunity by Fisher’s exact test. Multivariable logistic regression was used to identify clinical factors that correlate with native pertussis titers. RESULTS: Compared to controls, rheumatoid arthritis subjects had lower titers against pertussis, but not tetanus, and reduced immunity to pertussis. These results were even more prominent at 5–10 years post-vaccination, when rheumatoid arthritis patients had 50% lower titers than controls and 2.5x more rheumatoid arthritis subjects were not considered immune to pertussis. Multiple logistic regression demonstrated that female sex and methotrexate use, but not TNF inhibiting medications, correlated with reduced immunity to pertussis. Finally, rheumatoid arthritis patients had higher IgG titers against citrullinated pertussis than native pertussis. CONCLUSIONS: Pertussis titers are lower in vaccinated rheumatoid arthritis patients with evidence for contributions from female sex, a citrulline-biased immune response, and methotrexate use.