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Immunohematology and Genetic Testing (red cells, leukocytes and platelets)

Oral Abstract Spotlight Session - Discoveries in the Science of Immunohematology

#OA3-AM25-ST-28 - Diversity of RH and Antibody Development Following Transfusion in the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) Brazil Sickle Cell Disease Cohort

Saturday, October 25, 2025

10:45 AM - 12:15 PM PT

Room: SDCC 30AB

CE: N/A

Presenting Author(s)

Monike A. M Oliveira, MS

PhD Candidate
Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil
Osasco, Sao Paulo

Disclosure information not submitted.

Handouts

Background/Case Studies: RH diversity in individuals with sickle cell disease (SCD) poses transfusion challenges due to Rh alloimmunization. While some alleles encoding partial D or C phenotypes are known to increase risk for clinically significant Rh alloimmunization, the risk of antibody formation associated with other variant alleles is less clear. More data is needed to determine risk associated with combinations of RH variants. This study determined the frequency of RH variants in a large cohort of Brazilians with SCD and assessed Rh alloimmunization after RBC transfusion.

Study

Design/Methods: Whole genome sequencing (WGS) data from individuals with SCD enrolled in the REDS-III Brazil SCD cohort were analyzed. Patients were recruited (2013–2015) from four major blood centers in six Brazilian cities. WGS was performed using Illumina technology through the NHLBI Trans-Omics for Precision Medicine (TOPMed) consortium. RH variants were identified using bloodTyper, a custom software for WGS data analysis. Phenotype and alloimmunization data were provided by each center. Associations were assessed using Pearson’s Chi-squared test in R (v4.2.0).

Results/Findings: Among 2,626 individuals, 594 (22.6%) demonstrated RH variants. Most had RHCE variants (66.5%, n=395), followed by RHD (22.1%, n=131), or both (11.4%, n=68). Predicted partial antigen expression was c (11%), e (9.1%), D (7.6%), C (3.3%) and E (0.1%). The most frequent partial RHD variants were RHD*DAR3 (23.9%), RHD*DAR1 (20.7%) and RHD*DAU3 (10.8%). RHCE*ceVS accounted for 80% of RHCE variants, followed by RHCE*ceMO (5.4%). RBC alloimmunization was assessed in 2,070 transfused individuals. Rh antibodies were detected in 16.1% (n=334/2070), with similar frequencies in patients with RH variants (16.4%, n=75/457) and without (16.1%, n=259/1613). Rh antibodies directed against antigens present on the patient’s red cells were more frequent in patients with RH variants (42.7%, n=32/75) than those without (27.4%, n=71/259; p=0.017). In individuals with partial Rh antigens, 5.3% (n=24/457) had respective antibody, most commonly anti-C (9.5%) and anti-D (8.5%); anti-c was rare (0.9%) despite high partial c prevalence (10.9%). Anti-D and anti-C were mainly associated with RHD*DIIIa or DIIIa-ceVS(4-7)-D, respectively, in patients with partial antigens (Table).

Conclusions: Although RH variants were relatively common (22.6%) among our SCD cohort, only 5.3% of transfused individuals developed the corresponding Rh antibody. Molecular investigation of patients with SCD and C+ or D+ type may be a useful strategy, as most clinically significant alloimmunization involved alleles encoding partial C and partial D. The incidence of anti-c in patients with c variants was low, and in this cohort, RHD*DIIIa was the main variant associated with anti-D alloimmunization.