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Human leukocyte antigen association in idiopathic thrombotic thrombocytopenic purpura: evidence for an immunogenetic link
Author(s) -
SCULLY M.,
BROWN J.,
PATEL R.,
MCDONALD V.,
BROWN C. J.,
MACHIN S.
Publication year - 2010
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2009.03692.x
Subject(s) - human leukocyte antigen , immunology , thrombotic thrombocytopenic purpura , adamts13 , medicine , etiology , haplotype , antigen , allele , biology , gene , platelet , genetics
Summary. Background: Thrombotic thrombocytopenic purpura (TTP) is a rare, acute, life‐threatening disorder, associated with a deficiency in ADAMTS 13. The majority of acute, idiopathic, adult TTP cases are associated with anti‐ADAMTS 13 IgG antibodies. However, the factor(s) precipitating an acute TTP episode are not always obvious; indeed, a multifactorial etiology is likely. Objectives and Methods: DNA was used for human leukocyte antigen (HLA) class II typing, using polymerase chain reaction (PCR)–sequence‐specific primer and PCR–sequence‐specific oligonucleotide probe to methodology to investigate 50 European acquired idiopathic TTP cases. Results: There was an increase in the frequency of HLA‐DQB1*0301 (HLA‐DQ7) in patients with TTP as compared with controls [58.0% vs. 34.5% ( P = 0.048)]. The frequencies of HLA‐DRB1*11 and HLA‐DRB3* were also significantly increased in TTP patients as compared with controls [44.0% vs. 12.0% ( P = 0.0024) and 84.0% vs. 58.0% ( P = 0.024)], although it remains uncertain whether susceptibility is influenced by HLA‐DQ or HLA‐DR molecules or other genes in this haplotype. The frequencies of HLA‐DRB1*04 and HLA‐DRB4 (HLA‐DR53) were significantly decreased in the patient group as compared with controls [10.0% vs. 35.0% and 26.0% vs. 61.5% ( P = 0.0096 and P = 0.0024, respectively)], and may have a protective effect against the development of TTP. Conclusion: Analysis identified HLA class II types associated with susceptibility to and a protective effect against the development of acute acquired TTP in European patients. This provides the first description of a genetic factor predicting the risk of developing acquired antibody‐mediated TTP.