title: Particular association of clinical and genetic features with autoimmunity to citrullinated α-enolase in rheumatoid arthritis.
abstract: OBJECTIVE
  To confirm that the presence of anti-citrullinated α-enolase peptide 1 (anti-CEP-1) antibodies identifies a subgroup of patients with rheumatoid arthritis (RA).
  
  
  METHODS
  DNA and serum samples were obtained from 451 patients with RA and 279 healthy control subjects, all of whom were of Spanish ancestry. Antibodies to cyclic citrullinated peptide (CCP) and CEP-1 were measured by enzyme-linked immunosorbent assay. HLA-DRB1 and the R620W single-nucleotide polymorphism of PTPN22 were genotyped.
  
  
  RESULTS
  Anti-CEP-1 and anti-CCP antibodies were observed in 26.8% and 71.2% of the patients with RA, respectively. Most of the patients (86.6%) with anti-CEP-1 antibodies also had anti-CCP antibodies. Erosive arthritis, rheumatoid factor (RF) positivity, and the presence of the HLA shared epitope (especially the DRB1*04 alleles) were disproportionately associated with the group of patients with both antibodies. In addition, evidence of a significant interaction between the shared epitope and the risk allele of PTPN22 was observed only in these patients. In contrast, the association with these clinical and genetic features was weaker in patients with anti-CCP antibodies but lacking anti-CEP-1 antibodies. These results were obtained in patients in whom the prevalence of RA risk factors differed from that in other previously studied patients.
  
  
  CONCLUSIONS
  We observed that autoimmunity against citrullinated α-enolase may identify a subset of patients with a higher frequency of joint erosions and RF positivity. In addition, we confirmed the disproportionately large effect of the susceptibility alleles of HLA-DRB1 and their interaction with PTPN22 in this subset of patients. These results extend, confirm, and generalize the evidence supporting the specificity of the anti-CEP-1 antibody-positive subgroup of patients with RA among anti-CCP antibody-positive patients with RA.
authors.affiliation: Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
authors.forename: Ariana
authors.initials: A
authors.lastname: Montes
authors.forename: Rebeca
authors.initials: R
authors.lastname: Dieguez-Gonzalez
authors.forename: Eva
authors.initials: E
authors.lastname: Perez-Pampin
authors.forename: Manuel
authors.initials: M
authors.lastname: Calaza
authors.forename: Antonio
authors.initials: A
authors.lastname: Mera-Varela
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gomez-Reino
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez
mesh_terms: D000368:Aged; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000235:genetics / Q000276:immunology; D010751:Phosphopyruvate Hydratase / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology; D015995:Prevalence; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics / Q000276:immunology; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D025521:Tumor Suppressor Proteins / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000939:Epitopes; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; D025521:Tumor Suppressor Proteins; C487763:cyclic citrullinated peptide; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase