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
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