Human leukocyte antigen association in idiopathic thrombotic thrombocytopenic purpura: evidence for an immunogenetic link

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.