• M Scully, J Brown, R Patel, V McDonald, C J Brown, and S Machin.
• Department of Haematology, University College of London Hospitals, and Haemostasis Research Unit, University College London, London, UK. m.scully@ucl.ac.uk
• J. Thromb. Haemost. 2010 Feb 1; 8 (2): 257-62.

BackgroundThrombotic 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 MethodsDNA 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.ResultsThere 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.ConclusionAnalysis 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.

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