Balsa, AlejandroCabezón, AranchaOrozco, GiselaCobo, TatianaMiranda-Carus, EugeniaLópez-Nevot, Miguel AngelVicario, José LuisMartín-Mola, EmilioMartín, JavierPascual-Salcedo, Dora2012-11-212012-11-212010-04-06Balsa A, Cabezón A, Orozco G, Cobo T, Miranda-Carus E, López-Nevot MA, et al. Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regulation of antibodies against citrullinated proteins and rheumatoid factor. Arthritis Res. Ther.; 12(2):R621478-6354http://hdl.handle.net/10668/634Journal Article; Research Support, Non-U.S. Gov't;INTRODUCTION The purpose of this study was to investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF). METHODS We studied 408 patients (235 with RA, 173 non-RA) and 269 controls. ACPA, RF and HLA-DR typing were determined. RESULTS We found an increased frequency of HLA DRB1 alleles with the shared epitope (SE) in ACPA-positive RA. Inversely, HLA DRB1 alleles encoding DERAA sequences were more frequent in controls than in ACPA-positive RA, and a similar trend was found for HLA DR3. However, these results could not be confirmed after stratification for the presence of the SE, probably due to the relatively low number of patients. These data may suggest that the presence of these alleles may confer a protective role for ACPA-positive RA. In RA patients we observed association between SE alleles and ACPA titers in a dose-dependent effect. The presence of HLA DR3 or DERAA-encoding alleles was associated with markedly reduced ACPA levels. No association between RF titers and HLA DR3 or DERAA-encoding alleles was found. CONCLUSIONS HLA DRB1 alleles with the SE are associated with production of ACPA. DERAA-encoding HLA-DR alleles and HLA DR3 may be protective for ACPA-positive RA.enSecuencias de AminoácidosArtritis ReumatoideAutoanticuerposEpítoposFemeninoMarcadores GenéticosPredisposición Genética a la EnfermedadAntígenos HLA-DRCadenas HLA-DRB1HumanosMasculinoMediana EdadPéptidos CíclicosConformación ProteicaFactor ReumatoideMedical Subject Headings::Diseases::Musculoskeletal Diseases::Joint Diseases::Arthritis::Arthritis, RheumatoidMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::AutoantibodiesMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::EpitopesMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype::Genetic MarkersMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to DiseaseMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Histocompatibility Antigens Class II::HLA-D Antigens::HLA-DR AntigensMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Histocompatibility Antigens Class II::HLA-D Antigens::HLA-DR Antigens::HLA-DR beta-Chains::HLA-DRB1 ChainsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Macrocyclic Compounds::Peptides, CyclicMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Molecular Conformation::Protein ConformationMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Autoantibodies::Rheumatoid FactorMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Amino Acid Sequence::Amino Acid Motifsresearch article20370905open access10.1186/ar29751478-6362