POS0422 A HISTORY OF CHLAMYDIAE INFECTION IN RHEUMATOID ARTHRITIS DEVELOPMENT

Abstract

BackgroundCurrent hypotheses for the ethiopathogenesis of rheumatoid arthritis (RA) postulate an infectious agent initiating autoimmunity, which is thought to be at the mucosal level. Chlamydiae infections have been previously associated to development of an acute inflammatory arthritis, which can become chronic in some patients. Chlamydia trachomatis was detected in synovial fluid and tissue of RA patients, at least in early disease, suggesting that this organism could be involved in initiating RA onset, at least in a subset of patients.ObjectivesTo investigate the association between Chlamydiae infection and the development of autoimmunity and pre-clinical manifestations associated with RA.MethodsThis study was performed in an ongoing prospective study of individuals genetically at risk of developing RA, namely first-degree relatives of RA patients (RA-FDR). Individuals without clinical evidence of RA are enrolled, and assessed yearly, clinically and biologically. We included all RA-FDRs who responded to a Chlamydiae infection questionnaire, and the exposure of interest was self-reported Chlamydiae infection. The primary outcome was autoimmunity associated with RA (seropositivity) defined by the presence of anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factors (RF) at the last visit. Seropositive inflammatory arthritis at the last visit was a secondary outcome. We used logistic regression to analyze univariable and multivariable associations, adjusting for age and gender as potential confounders.ResultsA total of 1254 RA-FDRs were analyzed, of which 168 (13.4%) had developed seropositivity. The prevalence of self-reported Chlamydia infection was significantly higher in seropositive individuals as compared to controls (17.9% versus 9.8%, P<0.01) (Table 1). A significant association between the self-reported history of Chlamydiae infection and the seropositivity was observed in both univariate and multivariate analyses (OR=2.00, 95% CI: 1.27-3.09; OR=1.91, 95% CI: 1.20-2.95, respectively). A sub-group of 48 RA-FDRs (4 %) presented inflammatory arthritis in conjunction with seropositivity. This subgroup, considered at highest risk for RA, reported significantly more often prior infections with Chlamydiae than the negative subgroup (20.8% versus 10.5%, P<0.05). The ORs for the association of self-reported history of Chlamydiae infection and inflammatory arthritis coupled to RA-associated autoimmunity were 2.23 (95% CI: 1.03-4.43, P<0.01, univariate analysis) and 1.91 (95% CI: 0.88-3.82, P=0.08, multivariate analysis).Table 1.A potential association between a self-reported history of Chlamydiae infection and RA developmentRA-FDR with a self-reported chlamydia infection anamnesis (n=1254)Study GroupsSelf-reported “infection”Univariate analysisMultivariate analysis1OR (95% CI)OR (95% CI)Seropositive RA-FDR (n=168)30 (17.9%)2.00** (1.27 - 3.09)1.91** (1.20 – 2.95)Seronegative RA-FDR (n=1063)104 (9.8%)RA-FDR with seropositive inflammatory arthritis2 (n=48)10 (20.8%)2.23* (1.03 – 4.43)1.91 (0.88 – 3.82)RA-FDR without seropositive inflammatory arthritis (n = 1206)127 (10.5%)1Logistic regression model adjusting for age and gender.2Seropositive inflammatory arthritis was defined by being either: seropositive RA; seropositive “arthritis” (defined by at least one swollen joint at physical examination); seropositive with MSUS (musculoskeletal ultrasound) inflammatory activity.* P-value < 0.05** P-value < 0.01ConclusionOur results suggest that a history of Chlamydiae infection may be a risk factor for the development of RA in a subset of individuals at genetic risk for the disease. Serological analyses to assess the prevalence of antibodies to C. trachomatis major outer membrane protein (MOMP) are under way to confirm these preliminary data.