ANTI-PEPTIDE ANTIBODIES SPECIFIC FOR THE HUMAN FIBRINOGEN. CHAIN COULD PLAY AN ESSENTIAL ROLE IN THE PROGNOSIS IN EARLY RHEUMATOID ARTHRITIS AND FAMILY RISK GROUPS

Background: Rheumatoid Arthritis (RA) is a chronic systemic and autoimmune disease. The identification of antibodies has contributed to understanding RA. Recently, anti-carbamylated protein antibodies are the new autoantibodies present in RA and have been associated with severity and detected before the onset of RA. However, it is not clear the precise target antigen of anti-CarP antibodies Objectives: To determine associations between the anti-carbamylated protein and peptides antibodies with genetic and rheumatic indexes in patients with early RA (eRA) and individuals with family history of RA (FDR) Methods: A cross-sectional study involving 51 eRA patients, according to ACR/EULAR 2010 and 124 FDR matched by sex and age with healthy controls (HC). Two peptides of fibrinogen beta chain (Anti-Ca-Fib2 and Anti-Ca-Fib3) and a peptide without modification were synthesized. Antibodies against carbamylated peptides were measured using in-house indirect ELISA. RF and anti-CCP by turbidimetry and ELISA, hs-CRP by chemiluminescence. ESR by capillary photometry, disease activity was measured by SDAI, DAS28, RAPID3, and disability was assessed using MDHAQ. HLA-DRB1 (shared epitope SE) typing was made using the Luminex 200 TM. The comparisons were performed by McNemar and Wilcoxon tests. The chi-squared and Fisher’s tests were used in categorical variables. The associations were evaluated by the Mann–Whitney U test or t-test and conditional logistic regressions Results: In FDR anti-Ca-Fib2 and anti-Ca-Fib3 were more frequent than HC (25.0% vs 14.5%, 34.7% vs 15.3% and 33.1% vs 11.3%, respectively). The anti-Ca-Fib2 antibodies were associated with the HLA DRB1 SE* 1501 allele (p=0.03), with non-SE *0901 allele (p=0.01) (Fig. 1), the anti-Ca-Fib3 was associated with positive RF (p=0.0012). The FDR condition was associated with the presence of anti-Ca-Fib3 (OR=4.7; 95%CI=1.8–11.7; p=0.001) and painful joints (OR=2.2; 95%CI=1.01–4.68; p=0.045). In eRA anti-Ca-Fib2 were more frequent 47.1% vs. 13.7% in HC (OR 6.6 95% CI: 1.97-35.0 p = 0.0005) showing a risk of present anti-Ca-Fib2 antibodies six times higher in patients, without no differences in the frequency of anti-Ca-Fib3 between patients and controls. The anti-Ca-Fib2 antibodies were associated with positive RF (p = 0.022) and with high positive anti-CCP (p = 0.032) additionally we observed association with HLA-DRB1 SE * 0405 (p = 0.050) and non SE alleles * 1501 (p = 0.026) and * 0407 (p = 0.010)(Fig.2). Anti-Ca-Fib3 were associated with DAS28 ESR (p = 0.046) and with the HLA-DRB1 SE * 1402 allele (p = 0.050) and non-SE *0301 allele (p = 0.025). We found an association between eRA diagnosis with the presence of anti-Ca-Fib2 (OR 6.72 95% CI: 1.09-41.38 p = 0.040) and positive anti-CCP (OR 7.94 95% CI: 1.44-43.77 p = 0.017) Conclusion: Anti-Ca-Fib3 and anti-Ca-Fib2 antibodies might have significant prognostic value because the relationship with joint inflammatory manifestations in FDR. These results suggest a role for these antibodies as early biomarkers of RA, probably including additional mechanisms related to other non-SE alleles, especially in high-risk individuals. Finally, the anti-peptide antibodies in the present study may represent a straightforward way to identify antibodies directed to a specific carbamylated target References: [1] Shi J, van Steenbergen HW, van Nies JAB, et al. Arthritis Res Ther. 2015;17(1) Acknowledgments: Hospital Militar Central (Grant 2015-047), the Government Institute of Science, Technology,and Innovation,Francisco Jose de Caldas—COLCIENCIAS(Grant No. 130865740792-2014) Disclosure of Interests: None declared