Red blood cell alloimmunization in patients with sickle cell disease: correlation with HLA and cytokine gene polymorphisms

BACKGROUND: The reason for the difference in susceptibility to red blood cell (RBC) alloimmunization among patients with sickle cell disease (SCD) is not clearly understood and is probably the result of multiple factors. Our hypothesis is that genetic polymorphisms are associated with RBC alloimmunization. STUDY DESIGN AND METHODS: We investigated the possible association of susceptibility to RBC alloimmunization with polymorphisms of HLA and cytokines genes in 161 SCD patients prior exposed to RBC transfusion. Cytokine gene polymorphisms were analyzed by polymerase chain reaction (PCR) and TaqMan assays. HLA Class I genotyping was performed using PCR-specific sequence of oligonucleotides. Polymorphism frequencies were compared using the Fisher's exact test. RESULTS: Our results revealed increased percentage of the A allele and the GA genotype of the TNFA 308G/A cytokine among alloimmunized patients when compared to nonalloimmunized patients (A allele, 16.4% vs. 6.8%, p 5 0.004; GA genotype, 32.8% vs. 11.7%, p 5 0.0021). In addition, the IL1B 2511Tallele and the IL1B 2511TTand CT genotype frequencies were overrepresented among alloimmunized patients (T allele, 53.0% vs. 37.5%, p50.0085; CT1TT genotypes, 81.82% vs. 60.87%, p 5 0.0071). In relation to HLA Class I, we found a higher frequency of HLA-DRB1* 15 among patients alloimmunized to Rh antigens when compared to nonalloimmunized patients (15.63% vs. 6.98%, p - 0.044). CONCLUSION: Brazilian SCD patients with the TNFA, IL1B, and HLA- DRB1 gene polymorphisms were at increased risk of becoming alloimmunized by RBC transfusions. These findings may contribute to the development of future therapeutic strategies for patients with SCD with higher susceptibility of alloimmunization.