title: HLA and Sjögren's syndrome susceptibility. A meta-analysis of worldwide studies.
abstract: The aim of this work was to identify common HLA Class II alleles contributing to primary Sjögren's syndrome (pSS) susceptibility worldwide and to analyze their biological implications through a binding prediction approach of peptides from major pSS auto-antigens. Case-control studies on HLA-DQ and HLA-DR in pSS were searched in various literature databases through April 2011 by a systematic review. The effect summary odds ratios and 95% confidence intervals were obtained by means of the random effect model. A total of 1166 cases and 6470 controls from 23 studies were analyzed. At the allelic level, DQA1*05:01, DQB1*02:01, and DRB1*03:01 alleles were found to be risk factors for disease. Conversely, the DQA1*02:01, DQA1*03:01 and DQB1*05:01 alleles were protective factors. The current study stresses the significant size effect HLA exhibits in the development of pSS. Analysis of susceptibility and protective alleles revealed physicochemical differences in critical amino acids located within the antigen-binding groove of DRβ, DQα and DQβ chains, allowing us to infer a mechanistic approach to understand the role of HLA in pSS and other autoimmune diseases.
authors: Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
authors: Paola
authors: P
authors: Cruz-Tapias
authors: Adriana
authors: A
authors: Rojas-Villarraga
authors: Shannon
authors: S
authors: Maier-Moore
authors: Juan-Manuel
authors: JM
authors: Anaya
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology; D019295:Computational Biology; D020022:Genetic Predisposition to Disease; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology; D011110:Polymorphism, Genetic; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology*; D000097585:SS-B Antigen; D000099207:SS-A Antigen
chemical_list: D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen