Association of HLA-DRB1*12 with red cell alloimmunization in transfusion-dependent thalassemia

Alloimmunization is a major complication in transfusion-dependent thalassemia (TDT), leading to difficulties in providing compatible blood and increasing transfusion-related morbidity. Genetic factors, particularly polymorphisms in human leukocyte antigen (HLA) class II genes, may influence individual susceptibility to alloantibody formation. This study investigated the association between selected HLA-DRB1 targets and alloimmunization in TDT patients from South Khorasan Province, Iran. In this cross-sectional case-control study, 74 patients with transfusion-dependent β-thalassemia were enrolled and classified as alloimmunized patients or non-alloimmunized transfused disease controls according to alloantibody formation. Targeted detection of HLA-DRB1*07:01, HLA-DRB1*10, and HLA-DRB1*12 was performed using PCR-SSP. Seven patients (9.5%) developed alloantibodies, with anti-E and anti-K being the most frequent specificities, and most alloimmunized patients were hyper-responders with multiple alloantibodies. HLA-DRB1*10 was detected in 3/7 alloimmunized patients and 1/67 non-alloimmunized controls (Fisher’s exact test, p = 0.002; OR = 49.50, 95% CI: 4.64–528.21). HLA-DRB1*12 was detected in 2/7 alloimmunized patients and in none of the non-alloimmunized controls (Fisher’s exact test, p = 0.008); because of the zero cell, a stable odds ratio could not be estimated. No statistically significant association was observed for HLA-DRB1*07:01. Given the small number of alloimmunized patients and sparse data, the observed associations should be interpreted as exploratory and hypothesis-generating. These preliminary findings suggest that selected HLA-DRB1 targets may be associated with alloimmunization in TDT patients from South Khorasan and warrant validation in larger, geographically diverse cohorts.