RHD positive haplotypes in D negative Europeans

Area of Science:

• Genetics
• Immunology
• Molecular Biology

Background:

• Blood group genotyping is crucial for prenatal diagnosis and post-transfusion assessments.
• Current genotyping methods lack the specificity of serology, particularly for antigen D.
• Unknown RHD alleles and their frequencies pose challenges in accurate blood typing.

Purpose of the Study:

• To identify and characterize novel RHD alleles in antigen D negative blood donations.
• To determine the population frequencies of these identified RHD alleles in Germans and Europeans.
• To develop an improved RHD genotyping strategy with enhanced accuracy.

Main Methods:

• Screening of 8,442 antigen D negative blood donations using RHD PCR-SSP.
• Further characterization of RHD PCR positive samples via exon-specific PCR-SSP or sequencing.
• Phenotypic checking and frequency determination of identified alleles in the German population.

Main Results:

• 50 RHD positive samples were detected, including 15 with new Del alleles and 30 with 14 different D negative alleles (5 previously known).
• Fourteen D negative alleles, potentially generated by gene conversion, had a cumulative frequency of 1:1,500 in the population.
• Five samples showed D+/- chimera, weak D, or partial D types missed by serology, leading to anti-D immunization in two recipients.

Conclusions:

• An improved RHD genotyping strategy was developed with a false-positive rate below 1:10,000.
• The number of characterized RHD positive antigen D negative and Del alleles was more than doubled.
• Population frequencies of these alleles in Europe were defined, enhancing transfusion safety and prenatal diagnostics.