Background/Purpose: Patients with rheumatoid arthritis, an autoimmune disease affecting ~1% of the population, have an increased risk of infection. Interestingly, data are mixed for response to vaccination with rheumatoid arthritis patients showing a reduced response to some vaccine antigens, but relatively normal antibody titers in response to others, like the highly efficacious tetanus vaccine. Little is known about the response to pertussis vaccination in rheumatoid arthritis, a concerning omission given the relatively low efficacy of the pertussis vaccine, the rise in pertussis infections in the last 20 years, and the increased susceptibility of rheumatoid arthritis patients to infection. The purpose of this study is to determine if pertussis titers are reduced in vaccinated subjects with rheumatoid arthritis versus controls as well as to determine if clinical factors in rheumatoid arthritis, including the use of immune suppressing medications, correlate with pertussis titers.

Methods: Serum from 98 subjects with seropositive rheumatoid arthritis not using rituximab (a B cell depleting drug) and 77 controls, all vaccinated within 10 years of serum collection with the Tdap (tetanus, diphtheria, and pertussis) vaccine, were selected from our biorepository. Serum was subjected to enzyme-linked immunosorbent assay to detect IgG titers against pertussis and tetanus toxoid. Titers were compared by unpaired t-test and the rates of immunity based on manufacturer cut-offs were compared by a Fisher’s exact test. Univariate and multivariate logistic regression was used to identify clinical factors that correlate with pertussis titers. A p value <0.05 was considered significant.

Results: Subjects with rheumatoid arthritis had significantly lower IgG titers against pertussis, but not tetanus, compared to controls and fewer rheumatoid arthritis subjects were immune to pertussis. At less than 5 years post-vaccination, there was no significant difference in pertussis titers between rheumatoid arthritis patients and controls. However, at 5-10 years post-vaccination, rheumatoid arthritis patients had 50% lower titers than controls and fewer rheumatoid arthritis subjects met immune thresholds. Multivariate regression demonstrated that rheumatoid arthritis, female sex, and longer length of time since vaccination correlated with lower than median pertussis titers. Interestingly, the use of leflunomide or methotrexate at the time of serum collection correlated with higher and lower than median pertussis titers, respectively. No correlation was seen between TNF-inhibiting medications and pertussis titer.

Conclusion: Patients with rheumatoid arthritis have lower IgG titers against pertussis, especially 5-10 years post-vaccination. Reduced titers could be due to the relatively low efficacy of the pertussis vaccine, a dysregulated immune system in rheumatoid arthritis, and/or the use of certain medications. Future studies are needed to determine the mechanism for reduced immunity to pertussis, if more frequent vaccination would improve titers against pertussis, and if susceptibility to pertussis infection is increased in patients with rheumatoid arthritis.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduced-antibody-titers-against-pertussis-in-rheumatoid-arthritis/