PMID- 25993664 OWN - NLM STAT- MEDLINE DCOM- 20160418 LR - 20221207 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 5 DP - 2015 TI - HLA Class I and II Blocks Are Associated to Susceptibility, Clinical Subtypes and Autoantibodies in Mexican Systemic Sclerosis (SSc) Patients. PG - e0126727 LID - 10.1371/journal.pone.0126727 [doi] LID - e0126727 AB - INTRODUCTION: 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. CONCLUSION: 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. FAU - Rodriguez-Reyna, Tatiana S AU - Rodriguez-Reyna TS AD - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. FAU - Mercado-Velazquez, Pamela AU - Mercado-Velazquez P AD - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. FAU - Yu, Neng AU - Yu N AD - HLA laboratory, The American Red Cross Northeast Division, Dedham, Massachusetts, United States of America. FAU - Alosco, Sharon AU - Alosco S AD - HLA laboratory, The American Red Cross Northeast Division, Dedham, Massachusetts, United States of America. FAU - Ohashi, Marina AU - Ohashi M AD - HLA laboratory, The American Red Cross Northeast Division, Dedham, Massachusetts, United States of America. FAU - Lebedeva, Tatiana AU - Lebedeva T AD - HLA laboratory, The American Red Cross Northeast Division, Dedham, Massachusetts, United States of America. FAU - Cruz-Lagunas, Alfredo AU - Cruz-Lagunas A AD - Department of Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico. FAU - Nunez-Alvarez, Carlos AU - Nunez-Alvarez C AD - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. FAU - Cabiedes-Contreras, Javier AU - Cabiedes-Contreras J AD - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. FAU - Vargas-Alarcon, Gilberto AU - Vargas-Alarcon G AD - Basic and Technological Research Subdirection, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico. FAU - Granados, Julio AU - Granados J AD - Transplant Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. FAU - Zuniga, Joaquin AU - Zuniga J AD - Department of Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico. FAU - Yunis, Edmond AU - Yunis E AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150520 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Autoantibodies) RN - 0 (HLA-DQ beta-Chains) RN - 0 (HLA-DQB1 antigen) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Histocompatibility Antigens Class II) RN - EC 5.99.1.- (DNA Topoisomerases) SB - IM MH - Alleles MH - Autoantibodies/*immunology MH - Black People/genetics MH - Case-Control Studies MH - DNA Topoisomerases/metabolism MH - Demography MH - Disease Susceptibility/immunology MH - Female MH - HLA-DQ beta-Chains/immunology MH - Histocompatibility Antigens Class I/*immunology MH - Histocompatibility Antigens Class II/*immunology MH - Humans MH - Male MH - Mexico MH - Middle Aged MH - Principal Component Analysis MH - Scleroderma, Systemic/*classification/*immunology MH - White People/genetics PMC - PMC4439150 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/05/23 06:00 MHDA- 2016/04/19 06:00 PMCR- 2015/05/20 CRDT- 2015/05/21 06:00 PHST- 2015/01/08 00:00 [received] PHST- 2015/04/07 00:00 [accepted] PHST- 2015/05/21 06:00 [entrez] PHST- 2015/05/23 06:00 [pubmed] PHST- 2016/04/19 06:00 [medline] PHST- 2015/05/20 00:00 [pmc-release] AID - PONE-D-15-00854 [pii] AID - 10.1371/journal.pone.0126727 [doi] PST - epublish SO - PLoS One. 2015 May 20;10(5):e0126727. doi: 10.1371/journal.pone.0126727. eCollection 2015.