Functional Disability to Evaluate the Risk of Arthritis in First-degree Relatives of Patients With Rheumatoid Arthritis

Abstract

Objective The events that occur prior to the onset of rheumatoid arthritis (RA) continue to be delineated. We examined the relationship between self-reported joint symptoms, functional disability, and anticitrullinated protein antibody (ACPA) status in a cohort of first-degree relatives (FDR) of patients with RA who are at risk of future disease development. Methods We studied a cohort of 279 FDR of First Nations (FN) patients with RA who are at increased risk for future RA development, and analyzed data collected at their enrollment study visit. In parallel, we analyzed data from 279 FN subjects with no family history of RA. A subset of FDR developed inflammatory arthritis and we analyzed longitudinal data in this group. Results The prevalence of joint symptoms and functional disability was higher in FDR compared to non-FDR (all P < 0.001). Difficulty walking (37.3% vs 18.0%) and modified Health Assessment Questionnaire (HAQ) results were higher in ACPA-positive FDR compared to ACPA-negative FDR, and HAQ was independently associated with ACPA seropositivity (OR 2.79, 95% CI 1.56–5.00). Longitudinally, in individuals who developed ACPA-positive RA, ACPA level and HAQ score were significantly associated (R = 0.45, P < 0.001) in the preclinical period. Conclusion Compared to population-based controls, FDR have a high burden of joint symptoms and functional disability. Functional disability was most closely associated with ACPA seropositivity in the FDR, suggesting a direct role for ACPA outside of the context of clinically detectable synovitis. HAQ appears to be particularly valuable in the assessment of individuals at risk for future RA development.

Predictive risk factors before the onset of familial rheumatoid arthritis: the Tatarstan cohort study

“…Indeed, the two most prevalent symptoms retrieved in our study were arthralgia and MCP arthralgia within pre-RA and FDR groups. Moreover, and similar to our study, it was previously reported that arthralgia was higher in FDR than in HC ( 16 ), that joint symmetry was at high risk among arthralgia in FDR from RA patients ( 17 ), and that symmetry takes place as the disease progresses and may be absent at the RA onset ( 18 ).…”

Increased frequency of TIGIT+ CD4 T Cell subset in autoantibody-positive first-degree relatives of patients with rheumatoid arthritis

“…Autoantibody data was unavailable for 2 RA patients. Neither of the two FDR groups had clinically detectable RA, although as we previously reported, joint symptoms were prevalent in this population irrespective of their seropositivity status ( 16 ). Of note, the aAb+ FDR group was comprised of 3 individuals who were positive for ACPA only (222.5 ± 83.2 U/mL; mean ± SD), 3 individuals who were positive for RF only (27.9 ± 8.9 IU/mL; mean ± SD), and 4 individuals who were positive for both ACPA (59.6 ± 21.9 U/mL) and RF (231.5 ± 331 IU/mL).…”

Lipoxygenase-derived oxylipins are enriched in anti-citrullinated protein antibody (ACPA)-positive individuals at risk for developing rheumatoid arthritis

“…Based on this testing, the following 2 groups were included in this study: ACPA + FDR ( N = 53) and ACPA − FDR ( N = 10), which served as the control group. Some of the FDR reported musculoskeletal pain in various locations, as we have documented in other publications [ 7 ]. Venous blood was collected into SST™ serum separation tubes (BD Vacutainer Systems) and centrifuged for serum separation as per the manufacturer’s instructions.…”