title: Study of the association between human leukocyte antigens (HLA) and pemphigus vulgaris in Brazilian patients.
abstract: BACKGROUND
  Pemphigus vulgaris is a mucocutaneous blistering autoimmune disease that manifests as painful blisters or erosions on the skin and/or mucosal surfaces. IgG autoantibodies target desmoglein, playing a major role in disease pathogenesis. Genetic predisposal to pemphigus vulgaris, especially the HLA DR and DQ alleles, has been known since the 1980s. The unique constitution of the Brazilian population favors exploratory genetic studies.
  
  
  METHODS
  The study group included 51 patients with a confirmed diagnosis of pemphigus vulgaris from a tertiary hospital in Sao Paulo city, Sao Paulo, southeast Brazil. DNA was extracted from peripheral blood, and HLA A, B, C, DR, and DQ typing was performed. The control group was composed of a database of 297 deceased donors from the city of São Paulo typed with the same method. The statistical significance level was adjusted using the Bonferroni correction depending on the phenotypic frequencies evaluated for HLA A, HLA B, HLA C, HLA DRB1, DQA1, and HLA DQB1.
  
  
  RESULTS
  The alleles HLA-B*57, HLA-C*15, HLA-DRB1*04:02, HLA-DRB1*08:04, HLA-DRB1*14:01, DQA1*03:01, DQB1*03:02, and DQB1*05:03 were associated with susceptibility. Alleles HLA DRB1*04:02 and HLA-DRB1*14:01 and their respective haplotypes DRB1*04-DQA1*03:01-DQB1*03:02, and DRB1*14-DQA1*01:01-DQB1*05:03 conferred a risk of the disease.
  
  
  CONCLUSIONS
  The DRB1*04:02 and DQB1*05:03 alleles are associated with pemphigus vulgaris in our study as well as in various populations. The association with HLA-DRB1*08:04 in our study was confirmed to be specific to this allele and not to linkage disequilibrium to any adjacent gene. The association between HLA-B*57 and pemphigus vulgaris is reported for the first time in the present study.
authors.affiliation: ENT Department of School of Medicine, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Julio M
authors.initials: JM
authors.lastname: Gil
authors.affiliation: ENT Department of School of Medicine, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Raimar
authors.initials: R
authors.lastname: Weber
authors.affiliation: Transplant Immunology and Immunogenetics Laboratory, Heart Institute (INCOR), School of Medicine, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Claudia B
authors.initials: CB
authors.lastname: Rosales
authors.affiliation: Transplant Immunology and Immunogenetics Laboratory, Heart Institute (INCOR), School of Medicine, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Helcio
authors.initials: H
authors.lastname: Rodrigues
authors.affiliation: ENT Department of School of Medicine, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Luiz U
authors.initials: LU
authors.lastname: Sennes
authors.affiliation: Transplant Immunology and Immunogenetics Laboratory, Heart Institute (INCOR), School of Medicine, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.affiliation: ENT Department of School of Medicine, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Azis
authors.initials: A
authors.lastname: Chagury
authors.affiliation: ENT Department of School of Medicine, Sao Paulo University, Sao Paulo, Brazil.
authors.forename: Ivan D
authors.initials: ID
authors.lastname: Miziara
mesh_terms: D000328:Adult; D000483:Alleles; D001938:Brazil; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010392:Pemphigus / Q000235:genetics* / Q000276:immunology
chemical_list: D006680:HLA Antigens; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D015236:HLA-C Antigens; C446264:HLA-C*15 antigen; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; C527195:HLA-DRB1*04 antigen; C553506:HLA-DRB1*04:02 antigen; C553508:HLA-DRB1*08:04 antigen; C541271:HLA-DRB1*14:01 antigen