Estimating the serological underrecognition of patients with weak or partial RHD variants.

Area of Science:

• Hematology
• Genetics
• Immunology

Background:

• RHD genotyping is crucial for managing patients with weak or discrepant RhD red blood cell (RBC) phenotypes.
• Many RHD variants are misclassified as D-negative or D-positive, complicating management.
• The serological recognition rates (RRs) for weak and partial RHD variants are not well-established.

Purpose of the Study:

• To characterize the serological recognition rates (RRs) of weak and partial RHD variants.
• To assess the effectiveness of different serological methods in detecting RHD variants.
• To provide data for improving RhD blood group management.

Main Methods:

• Utilized data from four US studies involving RHD genotyping for weak or discrepant RhD phenotypes.
• Calculated allele frequencies (AFs) for weak D types 1, 2, and 3 SNVs in White and Hispanic/Latino populations using gnomAD.
• Devised formulas to correct for overcounting in gnomAD and calculated genetic prevalences to determine serological RRs.

Main Results:

• Overall RRs for weak D types 1-3 were 17% in Whites and 12% in Hispanics/Latinos.
• For partial RHD variants in Black individuals, the overall RR was 11%, but DAR RR reached 80%.
• Gel-tube methods showed higher recognition for some variants (type 2, DAU5) compared to microplate, while anti-D was detected in a small percentage of recognized cases.

Conclusions:

• Over 80% of patients with weak or partial RHD variants remain serologically unrecognized based on allele frequencies.
• Despite low overall anti-D detection rates, enhanced recognition of partial RHD variants is clinically important.
• Current serological methods may not adequately identify all individuals with RHD variants, necessitating improved diagnostic approaches.