title: Human leukocyte antigen association in idiopathic thrombotic thrombocytopenic purpura: evidence for an immunogenetic link.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Haematology, University College of London Hospitals, and Haemostasis Research Unit, University College London, London, UK. m.scully@ucl.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Scully
authors.forename: J
authors.initials: J
authors.lastname: Brown
authors.forename: R
authors.initials: R
authors.lastname: Patel
authors.forename: V
authors.initials: V
authors.lastname: McDonald
authors.forename: C J
authors.initials: CJ
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Machin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015551:Autoimmunity / Q000235:genetics*; D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D059845:HLA-DRB4 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000235:genetics* / Q000276:immunology; D011697:Purpura, Thrombotic Thrombocytopenic / Q000235:genetics* / Q000276:immunology; D012008:Recurrence; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069546:HLA-DQ7 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C508422:HLA-DRB1*11 antigen; D059826:HLA-DRB3 Chains; D059845:HLA-DRB4 Chains