Red blood cell (RBC) transfusion remains the cornerstone for treating patients with sickle cell disease (SCD). While most patients with SCD do not form alloantibodies even after several transfusions, other “responder” SCD patients are more susceptible. While pro-inflammatory conditions have been shown to increase the risk for alloimmunization, other genetic and environmental factors likely contribute as well. In order to assess the role genetic factors play, researchers genotyped approximately 2.3 million single nucleotide polymorphisms (SNPs) in 288 patients with SCD—154 responders and 134 non-responders. Based on genome-wide association analysis (GWAS), one locus (rs75853687) on chromosome 5 was found to be associated with alloantibody formation. The associated SNP variant is rare outside of African populations, and the locus overlaps a putative cis-acting enhancer that may be involved with immune regulation. Further studies are required in order to determine if other genetic loci are associated with alloimmunization.
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