Background/Purpose: The preclinical stage of Rheumatoid Arthritis (RA) is characterized by seropositivity for anti-citrullinated protein antibodies (ACPA). We (PubMed ID 30861615), and others, have shown that ACPA seropositivity is prevalent in the first-degree relatives (FDR) of RA patients. While ACPA is highly predictive of RA development in individuals who were selected by healthcare providers based on having joint symptoms such as arthralgia, the association between ACPA and self-reported symptoms in an unselected population of at-risk FDR has not been well studied. Because it has been proposed that the ACPA themselves may induce joint symptoms in the absence of joint inflammation, we sought to determine whether ACPA seropositivity is associated with self-reported symptoms and functional impairment in a large, unselected, cohort of at-risk Indigenous North American (INA) FDR of RA patients.  

Methods: Baseline demographics, Health Assessment Questionnaire (HAQ), and arthritis symptom survey data were obtained from a cohort of 607 unaffected FDR of RA patients. ACPA were detected using commercial kits (CCP2 or CCP3.1) and the manufacturer’s cut-off was used to define seropositivity. Associations between ACPA status and the self-report variables were analyzed by unsupervised univariate correlation, followed by logistic regression to identify variables that were independently associated with ACPA seropositivity.   

Results: 51 (8.4%) individuals were ACPA positive at baseline. Because smoking was prevalent in the cohort (85.4%), we were not able to demonstrate a clear relationship with ACPA seropositivity.  Although joint symptoms were common amongst FDR (53.6%), they were not associated with ACPA seropositivity. Mean HAQ scores were higher in ACPA positive individuals compared to ACPA negative (0.313 vs 0.197, p = 0.14), but this did not reach statistical significance. Unexpectedly, we found that compared to FDR from urban settings, FDR from rural communities were twice as likely to be ACPA seropositive (11.5% vs. 5.2%, p < 0.001). Logistic regression modelling showed that Rural status (odds ratio (OR) 3.2, 1.5 to 7.6), Difficulty lifting a glass (OR 4.3, 1.1 to 17.2), and Difficulty walking on a flat surfaces (OR 2.9, 1.1 to 7.6) were independently associated with ACPA seropositivity, after adjusting for age and sex.   

Conclusion: Although we were unable to demonstrate a relationship between joint symptoms and ACPA seropositivity, functional disability is associated with ACPA, even in the absence of detectable joint inflammation. The discordance in ACPA seropositivity between rural and urban locations is intriguing and warrants further investigation. 

ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-citrullinated-protein-antibodies-are-associated-with-functional-disability-in-unaffected-first-degree-relatives-of-rheumatoid-arthritis-patients/