Autoantibodies are a key feature of rheumatoid arthritis (RA) and a useful marker in the diagnosis and classification of the disease, as well as to determine its severity and development.

Previous research indicates that they may play an important role in the pathophysiology of RA. In an effort to assess the relationships between antibodies against carbamylated protein (anti-CarP) antibodies, anticitrullinated protein antibodies (ACPA), genetic factors (HLA-DRB1 alleles and PTPN22), and smoking in RA, Xia Jiang, Institute of Environmental Medicine, Kar­olinska Institutet, Stockholm, Sweden, and colleagues determined the presence of antibodies to CarP–fetal calf serum (FCS) and fibrinogen (CarP-Fib) in 846 patients with RA from the Leiden Early Arthritis Clinic (EAC), and almost 2000 patients with RA from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA).

“The detection of autoantibodies in sera of RA patients has opened up possibilities of subgrouping the RA population to allow more precise prognosis and possibly therapeutic management,” according to the investigators.

Using enzyme-linked immunosorbent assays, Dr Jiang and colleagues evaluated the frequency of anti-CarP as it relates to anti–cyclic citrullinated protein (CCP) immunoglobulin G in patients with RA and found that antibodies to CarP-FCS and CarP-Fib existed in both cohorts. Anti-CarP antibody positivity was observed in 49% to 73% of patients with anti–CCP-positive RA, and in 8% to 14% of patients with anti–CCP-negative RA—the differences were statistically significant.

In addition, the researchers further analyzed the impact of HLA-DRB1 alleles on disease risk in different types of RA and found a significant strong risk effect in anti–CCP-positive RA. This finding was observed regardless of anti-CarP antibody status, in both EIRA and EAC cohorts, as well as in the meta-analysis that was observed, the study authors noted.

Taking a closer look at the association of different HLA-DRB1 alleles and disease risk in different RA subsets, they found that several alleles, including HLA-DRB1*03 and HLA-DRB1*07, were associated with protection against anti–CCP-positive RA, especially in double-positive (CCP+/CarP+) subgroups. These data were collected through unstratified analyses, however, and after stratification, only HLA-DRB1*13 alleles showed protective effects.

The investigators also evaluated a subset of patients with ACPA-negative RA. No association was observed between anti-CarP antibodies and smoking, PTPN22 genotype variants, or HLA-DRB1 alleles; an association was, however, observed between anti–CarP-FCS antibodies and HLA-DRB1*03.

“These data suggest that anti-CarP antibody induction may be facilitated by different mechanisms than the ones involved in the induction of ACPA,” Dr Jiang and colleagues explained. No specific association between anti-CarP antibodies with other HLA-DRB1 alleles, PTPN22 genotypes, or smoking was seen after further analysis was performed.

Overall, data by Dr Jiang and colleagues indicate that different biological mechanisms may be associated with the formation of anti-CarP versus anti-CCP antibodies in patients with ACPA-positive and ACPA-negative RA.

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