title: Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis.
abstract: BACKGROUND
  Epstein-Barr virus exposure appears to be an environmental trigger for rheumatoid arthritis that interacts with other risk factors. Relationships among anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status have been observed in patients with rheumatoid arthritis from different populations.
  
  
  OBJECTIVE
  To perform an association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status in Brazilian patients with rheumatoid arthritis.
  
  
  METHODS
  In a case-control study, 140 rheumatoid arthritis patients and 143 healthy volunteers who were matched for age, sex, and ethnicity were recruited. Anti-Epstein-Barr nuclear antigen-1 antibodies and anti-cyclic citrullinated peptide antibodies were examined using an enzyme-linked immunosorbent assay, and shared epitope alleles were identified by genotyping. Smoking information was collected from all subjects. A comparative analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status was performed in the patient group. Logistic regression analysis models were used to analyze the risk of rheumatoid arthritis.
  
  
  RESULTS
  Anti-Epstein-Barr nuclear antigen-1 antibodies were not associated with anti-cyclic citrullinated peptide antibodies, shared epitope alleles, or smoking status. Anti-cyclic citrullinated peptide antibody positivity was significantly higher in smoking patients with shared epitope alleles (OR = 3.82). In a multivariate logistic regression analysis using stepwise selection, only anti-cyclic citrullinated peptide antibodies were found to be independently associated with rheumatoid arthritis (OR = 247.9).
  
  
  CONCLUSIONS
  Anti-Epstein-Barr nuclear antigen-1 antibodies did not increase the risk of rheumatoid arthritis and were not associated with the rheumatoid arthritis risk factors studied. Smoking and shared epitope alleles were correlated with anti-cyclic citrullinated peptide-antibody-positive rheumatoid arthritis. Of the risk factors, only anticyclic citrullinated peptides antibodies were independently associated with rheumatoid arthritis susceptibility.
authors.affiliation: Department of Rheumatology, University of Campinas, Campinas, SP, Brazil. m-yazbek@uol.com.br
authors.forename: Michel Alexandre
authors.initials: MA
authors.lastname: Yazbek
authors.forename: Silvia de
authors.initials: Sd
authors.lastname: Barros-Mazon
authors.forename: Cláudio Lúcio
authors.initials: CL
authors.lastname: Rossi
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Londe
authors.forename: Lilian Tereza Lavras
authors.initials: LT
authors.lastname: Costallat
authors.forename: Manoel Barros
authors.initials: MB
authors.lastname: Bertolo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000914:Antibodies, Viral / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000097:blood / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide