title: HLA-DRB1 shared epitope alleles in patients with rheumatoid arthritis: relation to autoantibodies and disease severity in a south Indian population.
abstract: OBJECTIVE
  To investigate the presence of the 'shared epitope' (SE) in the HLA-DRB1 alleles in patients with RA and to ascertain the frequency of the HLA-DRB1 alleles with autoantibodies (anti-cyclic citrullinated peptide [anti-CCP] rheumatoid factor [RF]) and disease severity.
  
  
  METHODS
  A total of 200 RA patients and 200 apparently healthy subjects participated in the study. HLA-DRB1 were genotyped using polymerase chain reaction with sequence-specific primer (PCR-SSP). Anti-CCP and RF in serum were determined by in vitro quantitative enzyme-linked immunosorbent assay (ELISA) method. Erythrocyte sedimentation rate (ESR) was measured by Westergren method. Disease activity was assessed by using the disease activity score-28 (DAS-28). Chi-square test and Student's t-test were used in the statistical analysis.
  
  
  RESULTS
  A significant increase in the frequency of HLA-DRB1*01, *04, *10 and *14 were identified in RA patients and showed a strong association with the disease susceptibility. While the frequencies of HLA-DRB1*03, *07, *11 and *13 were significantly lower in RA patients than in controls. The other HLA-DRB1 alleles *08, *09, *12, *15 and *16 showed no significant difference. The frequency of anti-CCP and RF antibodies did not showed significant difference in SE-positive patients compared with SE-negative patients. DAS-28 values of RA patients showed no significant difference between SE-positive and SE-negative groups.
  
  
  CONCLUSIONS
  Our results indicate that HLA-DRB1*01, *04, *10 and *14 alleles are related with RA, while HLA-DRB1*03, *07, *11 and *13 protect against RA in our population. On the other hand, we failed to provide evidence for the association of the autoantibodies and DAS-28 with SE-positive RA patients.
authors.affiliation: Department of Biochemistry, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Chennai, India.
authors.forename: Vasanth
authors.initials: V
authors.lastname: Konda Mohan
authors.affiliation: Department of Biochemistry, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Chennai, India.
authors.forename: Nalini
authors.initials: N
authors.lastname: Ganesan
authors.affiliation: Arthritis and Rheumatism Care Centre, Chennai, India.
authors.forename: Rajasekhar
authors.initials: R
authors.lastname: Gopalakrishnan
authors.affiliation: Department of Human Genetics, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Chennai, India.
authors.forename: Vettriselvi
authors.initials: V
authors.lastname: Venkatesan
mesh_terms: D000328:Adult; D000075422:Anti-Citrullinated Protein Antibodies / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics*; D007194:India; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D012217:Rheumatoid Factor / Q000097:blood*; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D000075422:Anti-Citrullinated Protein Antibodies; D015415:Biomarkers; D059811:HLA-DRB1 Chains; D016056:Immunodominant Epitopes; D012217:Rheumatoid Factor
keywords: 
  HLA-DRB1
  ; 
  RF
  ; anti-CCP; rheumatoid arthritis; shared epitope