title: The Protective Role of HLA-DRB1(∗)13 in Autoimmune Diseases.
abstract: Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB1(∗)15 (OR = 2.17) and HLA-DRB1(∗)03 (OR = 1.81) alleles with MS, HLA-DRB1(∗)03 with SLE (OR = 2.49), HLA-DRB1(∗)01 (OR = 1.79) and HLA-DRB1(∗)04 (OR = 2.81) with RA, HLA-DRB1(∗)07 with Ps + PsA (OR = 1.79), HLA-DRB1(∗)01 (OR = 2.28) and HLA-DRB1(∗)08 (OR = 3.01) with SSc, and HLA-DRB1(∗)03 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB1(∗)13 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB1(∗)13 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB1(∗)13, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB1(∗)13 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection.
authors.affiliation: Immunogenetics Laboratory, Instituto de Ciências Biomédicas Abel Salazar-Universidade do Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Bettencourt
authors.affiliation: Immunogenetics Laboratory, Instituto de Ciências Biomédicas Abel Salazar-Universidade do Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Carvalho
authors.affiliation: Immunogenetics Laboratory, Instituto de Ciências Biomédicas Abel Salazar-Universidade do Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Leal
authors.affiliation: Immunogenetics Laboratory, Instituto de Ciências Biomédicas Abel Salazar-Universidade do Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Brás
authors.affiliation: Immunogenetics Laboratory, Instituto de Ciências Biomédicas Abel Salazar-Universidade do Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal.
authors.forename: Dina
authors.initials: D
authors.lastname: Lopes
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Department of Neurology, Centro Hospitalar do Porto-Hospital de Santo António (CHP-HSA), Largo Prof. Abel Salazar, 4099-001 Porto, Portugal ; Unidade de Imunologia Clínica (UIC), Centro Hospitalar do Porto-Hospital de Santo António (CHP-HSA), Largo Prof. Abel Salazar, 4099-001 Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Martins da Silva
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Department of Neurology, Centro Hospitalar do Porto-Hospital de Santo António (CHP-HSA), Largo Prof. Abel Salazar, 4099-001 Porto, Portugal.
authors.forename: Ernestina
authors.initials: E
authors.lastname: Santos
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Department of Dermatology, Centro Hospitalar do Porto-Hospital de Santo António (CHP-HSA), Largo Prof. Abel Salazar, 4099-001 Porto, Portugal.
authors.forename: Tiago
authors.initials: T
authors.lastname: Torres
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Unidade de Imunologia Clínica (UIC), Centro Hospitalar do Porto-Hospital de Santo António (CHP-HSA), Largo Prof. Abel Salazar, 4099-001 Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Almeida
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Unidade de Imunologia Clínica (UIC), Centro Hospitalar do Porto-Hospital de Santo António (CHP-HSA), Largo Prof. Abel Salazar, 4099-001 Porto, Portugal ; Department of Internal Medicine, Centro Hospitalar do Porto-Hospital de Santo António (CHP-HSA), Largo Prof. Abel Salazar, 4099-001 Porto, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Farinha
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Barbosa
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Unidade de Imunologia Clínica (UIC), Centro Hospitalar do Porto-Hospital de Santo António (CHP-HSA), Largo Prof. Abel Salazar, 4099-001 Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Marinho
authors.affiliation: Department of Dermatology, Centro Hospitalar do Porto-Hospital de Santo António (CHP-HSA), Largo Prof. Abel Salazar, 4099-001 Porto, Portugal.
authors.forename: Manuela
authors.initials: M
authors.lastname: Selores
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Unidade de Imunologia Clínica (UIC), Centro Hospitalar do Porto-Hospital de Santo António (CHP-HSA), Largo Prof. Abel Salazar, 4099-001 Porto, Portugal ; Department of Internal Medicine, Centro Hospitalar do Porto-Hospital de Santo António (CHP-HSA), Largo Prof. Abel Salazar, 4099-001 Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Correia
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Unidade de Imunologia Clínica (UIC), Centro Hospitalar do Porto-Hospital de Santo António (CHP-HSA), Largo Prof. Abel Salazar, 4099-001 Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vasconcelos
authors.affiliation: Immunogenetics Laboratory, Instituto de Ciências Biomédicas Abel Salazar-Universidade do Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), Rua Alexandre Herculano No. 321, 4000-055 Porto, Portugal.
authors.forename: Paulo P
authors.initials: PP
authors.lastname: Costa
authors.affiliation: Immunogenetics Laboratory, Instituto de Ciências Biomédicas Abel Salazar-Universidade do Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal.
authors.forename: Berta Martins
authors.initials: BM
authors.lastname: da Silva
mesh_terms: D000483:Alleles; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D016017:Odds Ratio
chemical_list: D059811:HLA-DRB1 Chains; C506473:HLA-DRB1*13 antigen