HLA-DR4-Ala74 beta is associated with risk and poor outcome of severe aplastic anemia.
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 DR beta 1 chain (HLA-DR4-Ala74 beta 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-Ala74 beta subtype confers susceptibility to SAA independently from the DRB1*1501 allele. Finally, examination of the clinical records has shown that the HLA-DR4-Ala74 beta subtype is associated with poor outcome of SAA.
Department of Biochemistry, Research Institute of Hematology and Transfusiology, 2nd Sovietskaya St., 16 St. Petersburg, 193024, Russia. kapsi@mail.lanck.net
S I
SI
Kapustin
T I
TI
Popova
A A
AA
Lyshchov
E N
EN
Imyanitov
M N
MN
Blinov
K M
KM
Abdulkadyrov
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000453:epidemiology / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D017063:Outcome Assessment, Health Care; D012307:Risk Factors
D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains