CLINICAL SIGNIFICANCE OF ANTI-E IN SICKLE CELL DISEASE (SCD) PATIENTS UNDERGOING TRANSFUSION CARRYING THE RHCECEVS.01 AND RHCECEVS.02.01 VARIANT ALLELES

The genetic diversity of the RH locus in African populations contributes to the high prevalence of altered RHCE alleles and with high rate of Rh alloimmunization in SCD patients but the full clinical impact of alloimmunization associated with RH variants in these patients remains unclear as not all patients form alloantibodies and not all alloantibodies are implicated in hemolytic transfusion reactions when the carrier of the variant is exposed to the conventional antigen. It is unclear which variants are more likely to induce alloimmunization and which alloantibodies are clinically significant and capable of causing hemolytic transfusion reaction. Given that RHCE*ceVS.01 (RHCE* ce733G) and RHCE*ceVS.02.01 (RHCE* ce48C,733G ) are associated with the partial e-antigen and are the most commonly found variant alleles in our SCD patient population, we aimed to analyze the risk of anti-e formation in transfused patients carrying these variants exposed to conventional e-antigen. Additionally, we aimed to assess the clinical significance of the produced anti-e antibodies. We selected 61 patients with SCD receiving chronic and episodic transfusions with a history of ≥ 15 RBC transfusions (38 with RHCE*ceVS.01 and 23 with RHCE*ceVS.02.01). All patients were being transfused with Rh and K matched RBC units. RH genotyping was performed on all patients using the RHCE BeadChip array (BioArray, Immucor) and sequencing when necessary. Antibody screening and identification with autologous control were conducted using the gel test. Direct antiglobulin test (DAT), adsorption with autologous RBCs, and crossmatching with allogeneic partial e-antigen from donors carrying the same alleles were also performed when possible. To assess the clinical relevance of the alloanti-e produced we compared the patient's total Hb or HbA and HbS percentages at time of antibody detection with pretransfusion values and clinical suspicion of anemia and hemolysis. Among the 38 SCD patients with the RHCE*ceVS.01 variant allele, 5 were homozygous, 28 were heterozygous and 5 were compound heterozygous. Among the 23 patients with the RHCE*ceVS.02.01 variant allele, 8 were homozygous, 7 were heterozygous and 8 were compound heterozygous. Fifty percent of the patients with the RHCE*ceVS.01 allele developed alloanti-e, 23.7% autoanti-e and 26.3% did not develop anti-e. Fifty-two percent of the patients with the RHCE*ceVS.02.01 allele developed alloanti-e, 30.4% autoanti-e and 17.4% did not develop anti-