HLA-DR4-Ala74β is associated with risk and poor outcome of severe aplastic anemia.

Autor: Kapustin, S. I., Popova, T. I., Lyshchov, A. A., Imyanitov, E. N., Blinov, M. N., Abdulkadyrov, K. M.
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Zdroj: Annals of Hematology; Feb2001, Vol. 80 Issue 2, p66-71, 6p
Abstrakt: Severe aplastic anemia (SAA) is a heterogeneous hematological disorder with a high mortality. Genetic predisposition has been shown to play a role in a considerable proportion of SAA cases. For instance, the human lymphocyte antigen HLA-DR2 has been repeatedly demonstrated to be over-represented in SAA patients. In this paper, we expand on the evidence for the contribution of HLA polymorphism in the susceptibility to SAA, which was obtained using the "high-resolution" technique of HLA-DRB1 subtyping. The DRB1*1501 allele appeared to be responsible for the predominance of DR2 specificity in SAA patients and was the most significant risk factor for this disease. It was observed in 23/44 (52.3%) patients versus 22/100 (22.0%) donors [odds ratio (OR)=3.9; 95% confidence interval (CI): 1.8–8.3;P=0.0005, corrected P (Pc)<0.05]. In addition, DRB1*04 alleles also displayed non-random distribution in the SAA group. In particular, DRB1*04 variants coding for alanine at position 74 of the DRβ1 chain (HLA-DR4-Ala74β subtype) were detected in all 13 DR4-positive SAA patients but only in 15/24 (62.5%) controls (OR=16.6; 95% CI: 0.9–312.0;P=0.015). Multiple comparison analysis confirmed that the HLA-DR4-Ala74β subtype confers susceptibility to SAA independently from the DRB1*1501 allele. Finally, examination of the clinical records has shown that the HLA-DR4-Ala74β subtype is associated with poor outcome of SAA. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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