Epitopes described in "Multiple antibody reactivities to citrullinated antigens in sera from patients with rheumatoid arthritis: association with HLA-DRB1 alleles."

Article Authors:O Snir; M Widhe; C von Spee; J Lindberg; L Padyukov; K Lundberg; A Engström; P J Venables; J Lundeberg; R Holmdahl; L Klareskog; V Malmström
Article Title:Multiple antibody reactivities to citrullinated antigens in sera from patients with rheumatoid arthritis: association with HLA-DRB1 alleles.
Reference Detail
Reference ID:1014220
Abstract:BACKGROUND: Autoantibodies to cyclic citrullinated peptides (anti-CCP) are present in most patients with rheumatoid arthritis (RA), and associate with HLA-DRB1 shared epitope (SE) alleles. OBJECTIVE: To investigate reactivities of anti-CCP to various citrullinated proteins/peptides, which represent potential autoantigens in RA, and to examine the relationship between such antibodies, and their association with genetic variants within HLA-DRB1 SE alleles. METHODS: Serum samples from 291 patients with established RA and 100 sex- and age-matched healthy subjects were included in this study. Sera were first analysed for presence of anti-CCP antibodies and further for IgG and IgA antibodies towards candidate autoantigens in both their native and citrullinated form including: fibrinogen, alpha-enolase peptide-1 and the C1-epitope of type II collagen (C1(III)). Antibody specificity was confirmed by cross-reactivity tests. HLA-DR genotyping was performed. RESULTS: 72% of patients with RA were anti-CCP positive. Among the candidate autoantigens examined, IgG antibodies to citrullinated fibrinogen were found in 66% of patients' sera and in 41% for both citrullinated alpha-enolase peptide-1 and citrullinated C1(III). These antibodies were mainly seen in the anti-CCP-positive patient group; they were specific for their respective antigen and displayed limited cross reactivity. IgA responses were also detected, but less frequently than IgG. Anti-CCP and anti-citrullinated protein antibodies were associated with HLA-DRB1*04 rather than with HLA-DRB1*01 alleles. CONCLUSIONS: Antibodies directed against several citrullinated antigens are present in CCP-positive RA, with many patients displaying multireactivity. All specific reactivities were primarily associated with the HLA-DRB1*04 alleles, suggesting common pathways of anti-citrulline immunity.
Reference Type:Literature
PubMed ID:18635594
Journal:Ann Rheum Dis
Journal Volume:68
Article Pages:736-43
Journal ISSN:1468-2060
Article Chemical List:Autoantibodies;Autoantigens;Collagen Type II;DNA-Binding Proteins;HLA-DR Antigens;HLA-DRB1 Chains;Immunoglobulin A;Peptides, Cyclic;Tumor Markers, Biological;Tumor Suppressor Proteins;cyclic citrullinated peptide;Citrulline;Fibrinogen;ENO1 protein, human;Phosphopyruvate Hydratase
Article MeSH List:Adult; Aged; Aged, 80 and over; Alleles; Arthritis, Rheumatoid(genetics; immunology); Autoantibodies(blood); Autoantigens(immunology); Citrulline(immunology); Collagen Type II(immunology); Cross Reactions; DNA-Binding Proteins(immunology); Female; Fibrinogen(immunology); Genotype; HLA-DR Antigens(genetics); HLA-DRB1 Chains; Humans; Immunoglobulin A(biosynthesis); Male; Middle Aged; Peptides, Cyclic(immunology); Phosphopyruvate Hydratase(immunology); Tumor Markers, Biological(immunology); Tumor Suppressor Proteins(immunology); Young Adult
Curation Last Updated:2015-12-28 20:02:02