HLA-DQ7 Is Associated with Susceptibility to Idiopathic Thrombotic Thrombocytopenic Purpura.

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder associated with microangiopathic haemolytic anaemia, thrombocytopenia and multisystem microvascular thrombosis. It results from a deficiency of ADAMTS 13, required to cleave Ultra large von Willebrand factor multimers. An underlying autoimmune basis is suggested; indeed in up to 90% of idiopathic cases, antibodies, primarily IgG, to ADAMTS 13 can be demonstrated during an acute episode. Joseph et al( Am J Hematology 1994) reported that HLA-DR53 protects against TTP. In this study, twenty patients with idiopathic TTP, 6 male and 14 female, were typed for HLA-DR and DQ by PCR-SSP. Thirteen had recurrent (>3) episodes of TTP and all patients had ADAMTS 13 activity <5% with evidence of antibody to ADAMTS 13 at acute presentation. The HLA-DR and DQ frequencies in the patient group were compared with those found in 203 local blood donors and selected results are shown in the table below. In this study the reduction of DR53 has been confirmed, however, this may not be the primary HLA frequency altered in patients with TTP. Although HLA-DR53 is associated with DR4, DR7 and DR9, only the frequency of DR4 is reduced suggesting that this HLA type may be protective against TTP. The main finding of this study is that the frequency of HLA-DQ7 is significantly increased in the patient group. The frequency of HLA-DR11 (associated with DQ7), is also increased. However, four patients are DQ7 positive but negative for DR11 suggesting an association of DQ7 and susceptibility to TTP. Five patients are negative for HLA-DQ7; of these, four are HLA-DR15 positive, which may also contribute to susceptibility to TTP. HLA-DR and DQ associations with autoimmune disease, such as SLE and IDDM, have been well documented. The findings in this patient cohort suggest that specific HLA-DR and DQ molecules may have contributory roles in resistance or susceptibility to TTP. The repertoire of peptides presented to the immune system by HLA-DQ7 positive patients may increse their risk of developing TTP. HLA type and TTP HLA type % patients positive % controls positive P value DR4 5.0 35.0 0.01 DR11 50.0 12.3 0.001 DR15 45.0 27.1 NS DR53 35.0 63.5 0.05 DQ7 75.0 34.5 0.001