FRI0341 Anti-Carp Antibodies in Two Large Cohorts of Patients with Rheumatoid Arthritis and their Relationship to Genetic Risk Factors, Cigarette Smoking and Other Autoantibodies

Abstract

Background In rheumatoid arthritis (RA), several genetic risk factors and smoking are strongly associated with the presence of anti-citrullinated protein antibodies (ACPA), while much less is known about risk factors for ACPA-negative RA. Antibodies against carbamylated proteins (anti-CarP) have been described in both ACPA-positive and ACPA-negative RA patients. Objectives In this study we have analysed the relationships between anti-CarP antibodies, ACPA, genetic risk factors (HLA-DRB1 alleles and PTPN22) and smoking in RA. Methods Presence of antibodies to carbamylated fetal calf serum (CarP-FCS) and fibrinogen (CarP-Fib) was determined by in-house ELISAs in the Leiden Early Arthritis Cohort (EAC) and in the Swedish Epidemiological Investigation of RA (EIRA) cohort. Odds ratios for associations with different HLA-DRB1 alleles, PTPN22 genotypes and smoking were calculated separately for each cohort as well as in the combined meta-analysis, in RA subsets defined by anti-CarP and anti-cyclic citrullinated peptide (CCP) antibody status. Results In both cohorts, anti-CarP antibodies were mainly detected in the anti-CCP-positive population, but also in the anti-CCP-negative population. No associations between anti-CarP antibodies and HLA-DRB1 shared epitope alleles could be identified, while a consistent signal for an association between anti-CarP-FCS and HLA-DRB1*03 was observed. Further analyses did not reveal any specific associations of anti-CarP antibodies with other HLA-DRB1 alleles, PTPN22 genotypes or smoking. Conclusions Anti-CarP antibodies were present in both ACPA-positive and ACPA-negative RA. Except for a modest association with HLA-DRB1*03, there were no strong associations between anti-CarP antibodies and HLA-DRB1 alleles, PTPN22 or smoking. These data suggest that different biological mechanisms may underlie anti-CarP versus anti-CCP antibody formation. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4653