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.