title: HLA Class I and II Blocks Are Associated to Susceptibility, Clinical Subtypes and Autoantibodies in Mexican Systemic Sclerosis (SSc) Patients.
abstract: BACKGROUND
  Human leukocyte antigen (HLA) polymorphism studies in Systemic Sclerosis (SSc) have yielded variable results. These studies need to consider the genetic admixture of the studied population. Here we used our previously reported definition of genetic admixture of Mexicans using HLA class I and II DNA blocks to map genetic susceptibility to develop SSc and its complications.
  
  
  METHODS
  We included 159 patients from a cohort of Mexican Mestizo SSc patients. We performed clinical evaluation, obtained SSc-associated antibodies, and determined HLA class I and class II alleles using sequence-based, high-resolution techniques to evaluate the contribution of these genes to SSc susceptibility, their correlation with the clinical and autoantibody profile and the prevalence of Amerindian, Caucasian and African alleles, blocks and haplotypes in this population.
  
  
  RESULTS
  Our study revealed that class I block HLA-C*12:03-B*18:01 was important to map susceptibility to diffuse cutaneous (dc) SSc, HLA-C*07:01-B*08:01 block to map the susceptibility role of HLA-B*08:01 to develop SSc, and the C*07:02-B*39:05 and C*07:02-B*39:06 blocks to map the protective role of C*07:02 in SSc. We also confirmed previous associations of HLA-DRB1*11:04 and -DRB1*01 to susceptibility to develop SSc. Importantly, we mapped the protective role of DQB1*03:01 using three Amerindian blocks. We also found a significant association for the presence of anti-Topoisomerase I antibody with HLA-DQB1*04:02, present in an Amerindian block (DRB1*08:02-DQB1*04:02), and we found several alleles associated to internal organ damage. The admixture estimations revealed a lower proportion of the Amerindian genetic component among SSc patients.
  
  
  CONCLUSIONS
  This is the first report of the diversity of HLA class I and II alleles and haplotypes Mexican patients with SSc. Our findings suggest that HLA class I and class II genes contribute to the protection and susceptibility to develop SSc and its different clinical presentations as well as different autoantibody profiles in Mexicans.
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Rodriguez-Reyna
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Pamela
authors.initials: P
authors.lastname: Mercado-Velázquez
authors.affiliation: HLA laboratory, The American Red Cross Northeast Division, Dedham, Massachusetts, United States of America.
authors.forename: Neng
authors.initials: N
authors.lastname: Yu
authors.affiliation: HLA laboratory, The American Red Cross Northeast Division, Dedham, Massachusetts, United States of America.
authors.forename: Sharon
authors.initials: S
authors.lastname: Alosco
authors.affiliation: HLA laboratory, The American Red Cross Northeast Division, Dedham, Massachusetts, United States of America.
authors.forename: Marina
authors.initials: M
authors.lastname: Ohashi
authors.affiliation: HLA laboratory, The American Red Cross Northeast Division, Dedham, Massachusetts, United States of America.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Lebedeva
authors.affiliation: Department of Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cruz-Lagunas
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Núñez-Álvarez
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Cabiedes-Contreras
authors.affiliation: Basic and Technological Research Subdirection, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vargas-Alarcón
authors.affiliation: Transplant Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Julio
authors.initials: J
authors.lastname: Granados
authors.affiliation: Department of Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Zúñiga
authors.affiliation: Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Edmond
authors.initials: E
authors.lastname: Yunis
mesh_terms: D000483:Alleles; D001323:Autoantibodies / Q000276:immunology*; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D026942:DNA Topoisomerases / Q000378:metabolism; D003710:Demography; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D059866:HLA-DQ beta-Chains / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008297:Male; D008800:Mexico; D008875:Middle Aged; D025341:Principal Component Analysis; D012595:Scleroderma, Systemic / Q000145:classification* / Q000276:immunology*; D044465:White People / Q000235:genetics
chemical_list: D001323:Autoantibodies; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D026942:DNA Topoisomerases