DOI: 10.1093/rheumatology/kead682 ISSN: 1462-0324

A potential role for chlamydial infection in rheumatoid arthritis development

Celine Lamacchia, Romain Aymon, Brian C Hattel, Sebastien Aeby, Carole Kebbi-Beghdadi C, Benoit Gilbert, Olivia Studer, Jill M Norris, Michael V Nolers, M Kristen Demoruelle, Marie L Feser, LauraKay Moss, Delphine S Courvoisier, Kim Lauper, Kevin D Deane, Gilbert Greub G, Axel Finckh
  • Pharmacology (medical)
  • Rheumatology



To assess the relationship between self-reported and serologic evidence of prior chlamydial infection, rheumatoid arthritis (RA)-related autoantibodies and risk of RA-development.


This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA-FDR) who answered a question on past chlamydial infections. Primary outcome was systemic autoimmunity associated with RA (RA-autoimmunity) defined as positivity for anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF). Secondary outcomes were high levels of RA-autoimmunity, RA-associated symptoms and RA-autoimmunity, and subsequent seropositive RA diagnosis. We conducted a nested case-control analysis by measuring the serological status against Chlamydia trachomatis’ major outer membrane protein. We replicated our analysis in an independent United States-based RA-FDR cohort.


Among 1231 RA-FDRs, 168 (13.6%) developed RA-autoimmunity. Prevalence of self-reported chlamydial infection was significantly higher in individuals with RA-autoimmunity compared with controls (17.9% vs 9.8%, OR = 2.00, 95%CI: 1.27–3.09, p < 0.01). This association remained significant after adjustments (OR = 1.91, 95%CI: 1.20–2.95). Stronger effect sizes were observed in later stages of RA development. There was a similar trend between a positive C. trachomatis serology and high levels of RA-autoimmunity (OR = 3.05, 95% CI: 1.10–8.46, p= 0.032). In the replication cohort, there were significant associations between chlamydial infection and RF positivity and incident RA, but not anti-CCP positivity.


Self-reported chlamydial infections are associated with elevated RA-autoimmunity in at risk individuals. The differing association of chlamydial infections and ACPA/RF between cohorts will need to be explored in future studies but is consistent with a role of mucosal origin of RA-related autoimmunity.

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