HLA-DR2 frequency increase in severe aplastic anemia patients is mainly attributed to the prevalence of DR15 subtype

Abstract

The association between severe aplastic anemia (AA) and DR2 antigen seems to be well established. However, since discrimination between two DR2-associated splits, namely DR15 and DR16, rarely was performed, it remains unclear whether one or both of these subvariants are responsible for AA susceptibility. In this study, we have analyzed the HLA-DR allelic distribution in a group of 37 AA patients of slavic origin from North-Western Russia. The experimental design included PCR-based amplification of DRB-specific sequences, followed by reverse dot-blot hybridization of the biotinylated PCR-product with the set of sequence-specific oligonucleotide probes. HLA-DRB alleles were identified by non-radioactive enzymatic reaction, then standard serological specificities of HLA-DR antigen were estimated according to the WHO nomenclature. Whereas DR15 subtype occurred more often in the patients (23.0% vs. 13.3%, p< 0.05), DR16 split did not show the same tendency. The results, show the overall predominance of HLA-DR2 specificity (DR15+DR16) did not reach statistical significance (24.4% vs.17.5%, p<0.2). Thus, we conclude that repeatedly reported DR2 frequency increase in AA patients is mainly attributed to the prevalence of DR15 subtype.

Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria–type cells in bone marrow failure syndrome

“…This DR antigen has been repeatedly reported to be associated with susceptibility to AA. 20,21 The frequency of HLA-DR15 in PNH ϩ RA patients (90.5%) in the present study was higher than the frequency of HLA-DR2 (74%) in the recent study White blood cell, hemoglobin, and platelet counts were determined at the time of diagnosis. NCC indicates nucleated cell count; NT, not tested; and NE, not evaluable.…”

Diagnosis of acquired aplastic anemia

“…HLA-DR2 27 and particularly HLA-DRB1*15 (DRB1*1501 and DRB1*1502) 28 have been associated with some characteristics and to affect the outcome of AA. Patients possessing HLA-DR15 tend to be older and actually 450% of the patients with HLA-DRB1*1502 are older than 40 years of age.…”

The ancestry of the HLA–DRB1∗15 allele predisposes the Mexican mestizo to the development of aplastic anemia

“…Patients with this disease show pancytopenia in peripheral blood and hypoplasia in bone marrow, which in turn translates into the anemic syndrome, hemorrhages, and habitually serious infections and which can lead to death of the patient [3]. Epidemiological data worldwide show in Europe and USA an incidence of 0.8 and 1.5 new cases per million individuals per year respectively; in Mexico, the incidence is 3.9-4.2 new cases per million individuals per year [4].…”