Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Serum anti-citrullinated proteins (ACPA, including anti-CCP antibodies) and rheumatoid factor (RF) are critical diagnostic markers for RA, and are associated with more severe radiographic damage. The mechanisms of this association are unclear, but might involve serum cytokine levels, given our previous study reporting an association of IFN-γ receptor gene expression in peripheral blood mononuclear cells with radiographic damage in African-Americans with RA.
Methods: ACPA profiles (20 specificities) of 923 and cytokine profiles (17 cytokines) of 825 African-Americans with RA were generated from serum obtained at the time of enrollment into a large observational study. We stratified patents into four subgroups according to autoantibody positivity (CCP+/RF+, CCP+/RF-, CCP-/RF+, and CCP-/RF-). Associations of ACPA specificities and serum cytokine levels with radiographic severity were analyzed using a cross sectional approach, based on disease duration at the time of the enrollment: 0-12 months; 12-24 months; 24-48 months; 48-96 months; 96-120 months; and >120 months. The mean ± SE values of each subgroup of CCP and RF combination were analyzed and compared by student t-test. Correlations were analyzed using a zero-inflated binomial model (ZINB).
Results: After adjustment for disease duration at enrollment in the cohort, strong associations were found between radiographic scores and 11 of 20 ACPA specificities. Among patients with disease duration 0-48 months, radiographic scores were slightly higher for CCP+/RF+ compared to other subgroups. As expected, after 96 months of disease duration, the accrued radiographic damage was much higher in the double positive group compared to others subgroups. Almost all serum ACPA specificities were significantly higher at 0-48 months than at > 48 months disease duration. Among the CCP+/RF+ group, serum IL-1β, IL-6, and MCP-1 levels were higher as disease duration increased. Serum levels of IL-2, IL-5, IL-7, IL-12, IL-13 and IFN-γ were significantly higher in CCP+/RF+ compared to CCP-/RF- (p values <0.05). There was a strong association between total radiographic scores and log transformed serum IFN-γ levels (adjusted for age at disease onset, body mass index, and CCP status) (p = 0.0374, ZINB).
Conclusion: Our findings support the hypothesis that temporal changes in immunologic perturbations play a role in accumulated joint damage in RA. Specifically, the presence of ACPA specificities, the increasing elevation of IL-1β, IL-6, and MCP-1 over time, and elevated serum IL-2, IL-5, IL-7, IL-12, IL-13, and IFN-γ levels may contribute to the accrued joint damage in CCP+/RF+ patients. These findings may have important implications for stratifying African-Americans with RA according to risk of joint damage and may lead to different treatment strategies.
To cite this abstract in AMA style:Sun D, Robinson WH, Cui X, Laufer VA, Danila MI, Reynolds RJ, Raman C, Ledbetter S, Szalai A, Bridges SL Jr.. Associations of Serum Anti-Citrullinated Proteins and Cytokines with Radiographic Scores in African-American Rheumatoid Arthritis Patients [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/associations-of-serum-anti-citrullinated-proteins-and-cytokines-with-radiographic-scores-in-african-american-rheumatoid-arthritis-patients/. Accessed October 27, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/associations-of-serum-anti-citrullinated-proteins-and-cytokines-with-radiographic-scores-in-african-american-rheumatoid-arthritis-patients/