It has been confirmed that antibodies to citrullinated profilaggrin(306-324) may play important roles in RA. In this study, human papilloma virus (HPV)-47 E2(345-362), homologous to profilaggrin(306-324), was found using the NCBI BLAST program. Then, E2(345-362) and citrullinated E2(345-362), with arginine(348) 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 E2(345-362) peptide were similar in RA and other rheumatic diseases, those of antibodies to the citrullinated E2(345-362) 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 E2(345-362) peptide antibodies. Moreover, the prevalence of anti-CCP antibodies and that of anti-peptidylarginine deiminase (PAD14) antibodies in anti-citrullinated E2(345-362)-positive patients were all higher than those of anti-citrullinated E2(345-362)-negative patients. There were significant correlations between anti-citrullinated E2(345-362) and anti-PAD14. RA patients with antibodies to citrullinated E2(345-362) 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 PAD14 may make it easier to citrullinate the HPV-47 E2(345-362) peptide, leading to the subsequent immune responses. (C) 2008 Elsevier Ltd. All rights reserved.