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

J Thromb Haemost. 2010 Feb;8(2):257-62. doi: 10.1111/j.1538-7836.2009.03692.x. Epub 2009 Nov 17.


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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoimmunity / genetics*
  • Case-Control Studies
  • Child, Preschool
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA Antigens / genetics*
  • HLA-DQ Antigens / genetics
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • HLA-DRB3 Chains
  • HLA-DRB4 Chains
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Purpura, Thrombocytopenic, Idiopathic / genetics*
  • Purpura, Thrombocytopenic, Idiopathic / immunology
  • Purpura, Thrombotic Thrombocytopenic / genetics*
  • Purpura, Thrombotic Thrombocytopenic / immunology
  • Recurrence
  • Registries
  • Risk Assessment
  • Risk Factors
  • Young Adult


  • HLA Antigens
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQ7 antigen
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*11 antigen
  • HLA-DRB3 Chains
  • HLA-DRB4 Chains