Prevalence and significance of antibodies to citrullinated human papilloma virus-47 E2345–362 in rheumatoid arthritis

It has been confirmed that antibodies to citrullinated profilaggrin306–324 may play important roles in RA. In this study, human papilloma virus (HPV)-47 E2345–362, homologous to profilaggrin306–324, was found using the NCBI BLAST program. Then, E2345–362 and citrullinated E2345–362, with arginine348 replaced by citrulline, were synthesized. The presence of antibodies against these peptides was examined by an enzyme-linked immunosorbent assay. Associations between these antibodies and the clinical and laboratory features of RA were evaluated. Although the prevalence and AU value of antibodies to the E2345–362 peptide were similar in RA and other rheumatic diseases, those of antibodies to the citrullinated E2345–362 peptide were significantly higher in RA than in other rheumatic diseases. Additionally, sera that were preincubated with cyclic citrullinated peptide (CCP) demonstrated lower AU values of anti-citrullinated E2345–362 peptide antibodies. Moreover, the prevalence of anti-CCP antibodies and that of anti-peptidylarginine deiminase (PADI4) antibodies in anti-citrullinated E2345–362-positive patients were all higher than those of anti-citrullinated E2345–362-negative patients. There were significant correlations between anti-citrullinated E2345–362 and anti-PADI4. RA patients with antibodies to citrullinated E2345–362 had higher DAS28 scores, erythrocyte sedimentation rates, and radiographic progression than those without the antibodies. These results suggest that HPV-47 E2 may act as an autoantigen in RA. The increase in PADI4 may make it easier to citrullinate the HPV-47 E2345–362 peptide, leading to the subsequent immune responses.