Association of anti-citrullinated vimentin and anti-citrullinated α-enolase antibodies with subsets of rheumatoid arthritis.
OBJECTIVE
To determine whether the anti-citrullinated vimentin peptide 60-75 (anti-Cit-vimentin) and the immunodominant anti-citrullinated α-enolase peptide 1 (anti-CEP-1) antibodies are associated with subsets of patients with rheumatoid arthritis (RA) independently of the associations between anti-cyclic citrullinated peptide (anti-CCP) antibodies and clinical features of RA.


METHODS
The 3 antibody types were quantified by enzyme-linked immunosorbent assay (ELISA) in serum samples from 521 patients with RA and 173 healthy controls of Spanish ancestry. Genotypes for HLA-DRB1 alleles and rs2476601 in PTPN22 were available for these patients and controls plus an additional 106 healthy controls. A combined analysis of the 3 antibodies was conducted using stratified contingency tables and logistic regression models.


RESULTS
A differential, particularly strong, and independent association was observed between the presence of anti-Cit-vimentin antibodies and the presence of shared epitope (SE) alleles, specifically in patients carrying 2 SE alleles, and between the presence of anti- Cit-vimentin antibodies and the prevalence of joint erosion. Associations were observed between anti-CEP-1 positivity and the presence of HLA-DRB1 and PTPN22 risk alleles and their additive interaction. These associations were not accounted for by the anti-CCP status.


CONCLUSIONS
Our results indicate that the 2 antibodies against citrullinated peptides analyzed in this study add specific information beyond that obtained with the anti-CCP status. They define subgroups of patients with RA in which genetic factors have different weight and there is an observed difference in the prevalence of erosions.
Instituto de Investigacion Sanitaria and Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
Ariana
A
Montes
Eva
E
Perez-Pampin
Manuel
M
Calaza
Juan J
JJ
Gomez-Reino
Antonio
A
Gonzalez
D000328:Adult; D000483:Alleles; D000906:Antibodies / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D018450:Disease Progression; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000276:immunology*; D014746:Vimentin / Q000235:genetics / Q000276:immunology*
D000906:Antibodies; D000939:Epitopes; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide; D010751:Phosphopyruvate Hydratase