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

J Autoimmun. 2008 Sep;31(2):131-5. doi: 10.1016/j.jaut.2008.04.021. Epub 2008 Jun 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alphapapillomavirus / immunology*
  • Antibodies / blood*
  • Antibodies / immunology
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / immunology*
  • China / epidemiology
  • Citrulline*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Filaggrin Proteins
  • Humans
  • Intermediate Filament Proteins / immunology*
  • Male
  • Middle Aged
  • Peptides / immunology*
  • Prevalence
  • Reference Standards
  • Young Adult

Substances

  • Antibodies
  • Filaggrin Proteins
  • Intermediate Filament Proteins
  • Peptides
  • Citrulline