Association between HLA-DRB1*04, HLA-DQB1*03, and HLA-DQB1*06 with alloimmunization in transfusion-dependent patients with thalassemia: the first case-control study in Iran

Transfusion therapy is crucial for treating Transfusion-dependent thalassemia (TDT) patients. However, the production of Alloantibodies presents a substantial challenge for these individuals and impacts their quality of life. The Rh and Kell blood group antigens are particularly susceptible to alloantibody development. This study aims to establish the correlation between HLA-DRB1*04, HLA-DQB1*03, and HLA-DQB1*06 alleles and alloimmunzation in thalassemia patients from Iran. 98 thalassemic patients were recruited for this study (49 alloimmunized and 49 non-alloimmunized). Alloimmunized patients developed Rh and Kell specificities alloantibodies. The two groups were compared based on the results of HLA-DRB1 and HLA-DQB1 genotyping conducted using Sequence-Specific Primers (SSP-PCR). The findings from the antibody screening revealed that the predominant alloantibody detected was Anti-K (95.9%), Anti-E (65.3%), Anti-C (30.6%), Anti-D (28.6%), Anti-c (10.2%), Anti-e (2%), and Anti-k (2%). There was a notable difference in HLA-DQB1*03 between alloimmunized and non-alloimmunized groups, 41.8% vs. 58.2%, respectively. (iP = 0.001, OR = 0.135, CI = 0.036-0.499). There was not any notable relationship between HLA-DRB1*04 and HLA-DQB1*06 alleles and alloimmunization. Our findings indicate that HLA-DQB1*03 may have a protective role in preventing alloantibody production. Thus, HLA-typing, particularly focusing on DQB1*03, can significantly enhance the screening process, leading to improved blood transfusion management, reduced rejection of hematopoietic stem cell transplantation, and minimized blood transfusion complications.