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.
Department of Rheumatology and Immunology, People's Hospital, Peking University, 11 Xizhimen South Street, Beijing, China.
Jinxia
J
Shi
Xiaoyun
X
Sun
Yi
Y
Zhao
Jinxia
J
Zhao
Zhanguo
Z
Li
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000276:immunology*; D000906:Antibodies / Q000097:blood* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D002681:China / Q000453:epidemiology; D002956:Citrulline; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology*; D015995:Prevalence; D012015:Reference Standards; D055815:Young Adult
D000906:Antibodies; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D010455:Peptides; D002956:Citrulline