title: The role of human leukocyte antigen DRB1-DQB1 haplotypes in the susceptibility to acquired idiopathic thrombotic thrombocytopenic purpura.
abstract: The acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying ADAMTS13-deficiency is caused by inhibitory autoantibodies against the protease. Human leukocyte antigens (HLA), responsible for antigen presentation, play an important role in the development of antibodies. The loci coding HLA DR and DQ molecules are inherited in linkage as haplotypes. The c.1858C>T polymorphism of the PTPN22 gene, which codes a protein tyrosine phosphatase important in lymphocyte activation, predisposes to a number of autoimmune diseases. We determined the HLA-DRB1-DQB1 haplotypes and the PTPN22 c.1858C>T genotypes in 75 patients with acquired idiopathic TTP and in healthy controls, in order to assess the role of these genetic factors and their interactions in the susceptibility to TTP. We found that the carrier frequencies of the DRB1∗11-DQB1∗03 and DRB1∗15-DQB1∗06 haplotypes were higher, while those of the DRB1∗07-DQB1∗02 and DRB1∗13-DQB1∗06 haplotypes were lower in TTP patients. There was no difference in the overall frequency of the PTPN22 c.1858T allele between TTP patients and controls. In conclusion, we identified four HLA-DRB1-DQB1 haplotypes associated with an increased (DRB1∗11-DQB1∗03 and DRB1∗15-DQB1∗06) or a decreased (DRB1∗07-DQB1∗02 and DRB1∗13-DQB1∗06) susceptibility to acquired idiopathic TTP.
authors.affiliation: 3rd Dept. of Internal Medicine, Research Laboratory, Semmelweis University, Budapest, Hungary. Electronic address: gysinkovits@gmail.com.
authors.forename: György
authors.initials: G
authors.lastname: Sinkovits
authors.affiliation: 3rd Dept. of Internal Medicine, Research Laboratory, Semmelweis University, Budapest, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Szilágyi
authors.affiliation: 3rd Dept. of Internal Medicine, Research Laboratory, Semmelweis University, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Farkas
authors.affiliation: Laboratory of Transplantation Immunogenetics, Hungarian National Blood Transfusion Service, Budapest, Hungary.
authors.forename: Dóra
authors.initials: D
authors.lastname: Inotai
authors.affiliation: Laboratory of Transplantation Immunogenetics, Hungarian National Blood Transfusion Service, Budapest, Hungary.
authors.forename: Anikó
authors.initials: A
authors.lastname: Szilvási
authors.affiliation: Dept. of Pathophysiology, Semmelweis University, Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Tordai
authors.affiliation: Dept. of Internal Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Rázsó
authors.affiliation: Dept. of Haematology and Stem Cell Transplantation, United St. István and St. László Hospital, Budapest, Hungary.
authors.forename: Marienn
authors.initials: M
authors.lastname: Réti
authors.affiliation: 3rd Dept. of Internal Medicine, Research Laboratory, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
mesh_terms: D000071120:ADAMTS13 Protein / Q000276:immunology*; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D006814:Hungary; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics; D011697:Purpura, Thrombotic Thrombocytopenic / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D059866:HLA-DQ beta-Chains; D059811:HLA-DRB1 Chains; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D000071120:ADAMTS13 Protein
keywords: Gender; HLA-DRB1-DQB1 haplotypes; PTPN22 c.1858C>T polymorphism; Thrombotic thrombocytopenic purpura