title: HLA shared epitope and ACPA: just a marker or an active player?
abstract: Autoantibody production is genetically controlled and anti-citrullinated protein/peptide antibodies (ACPA) are not an exception to the rule. ACPA are highly specific markers of rheumatoid arthritis (RA) and are also associated with a more severe disease course. The production of ACPA is almost invariably observed in HLA-shared epitope (SE) positive patients. The DRB1 alleles sharing SE are those conferring susceptibility to RA. SE alleles behave like immune response genes, controlling both the specificity and the amount of ACPA produced. These data suggest a role of SE in the presentation of citrullinated antigens. The ability of SE alleles to bind selectively to citrullinated sequences as compared to the native counterparts has been demonstrated in the case of peptides derived from several joint associated proteins (vimentin, fibrinogen and cartilage intermediate-layer protein). On the contrary, EBV-derived citrullinated peptides do not display a biologically relevant binding to SE alleles even if the immune response to VCPs is under the genetic control of these alleles (namely *0401 and *0404). Thus, the presentation of citrullinated epitopes does not represent the only molecular mechanisms underlying the HLA-DRB1 effect on ACPA production.
authors: Clinical Immunology and Allergy Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy.
authors: Federico
authors: F
authors: Pratesi
authors: Elisabeth
authors: E
authors: Petit Teixeira
authors: John
authors: J
authors: Sidney
authors: Laetitia
authors: L
authors: Michou
authors: Ilaria
authors: I
authors: Puxeddu
authors: Alessandro
authors: A
authors: Sette
authors: Francois
authors: F
authors: Cornelis
authors: Paola
authors: P
authors: Migliorini
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics / Q000276:immunology; D017951:Antigen Presentation; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology; D002956:Citrulline / Q000378:metabolism*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000276:immunology*; D006801:Humans; D011506:Proteins / Q000378:metabolism*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D011506:Proteins; D002956:Citrulline