LOWER ANTIGEN SITE DENSITY AND WEAK-D IMMUNOGENICITY CANNOT BE EXPLAINED BY STRUCTURAL GENOMIC ABNORMALITIES OR REGULATORY DEFECTS OF THE RHD GENE

BACKGROUND: The weak D phenotype is characterized serologically by a w eak or negative agglutination reaction with polyclonal anti-D in an im mediate-spin test. Agglutination is enhanced in the indirect antiglobu lin test. Red cells that are typed weak D have a much lower number of apparently complete D antigens at their cell surface and are associate d with considerably weaker immunogenicity than are red cells with norm al D. In a previous study, the number of D sites per cell was determin ed in eight unrelated weak D individuals to range from 490 to 1870 D s ites per cell, which corresponded to 4 to 14.2 percent of the number o f D sites in CcDee samples. STUDY DESIGN AND METHODS: The RHD gene was investigated for structural abnormalities by Southern blot experiment s and polymerase chain reaction-based RHD typing in these individuals. In addition, abnormalities in the transcription process were studied by sequence analysis of RH transcripts and by comparing the relative a mounts of RHD mRNA in weak D to those in CcDee, CcDEe, and -D- samples by using a semiquantitative reverse transcriptase-polymerase chain re action analysis. RESULTS: The RHD gene in weak D phenotypes does not s how any abnormalities at either the genomic or the transcriptional lev el when compared to the RHD gene in normal D phenotypes. CONCLUSION: T he weaker immunogenicity of weak D is not explained by structural diff erence in the RHD gene itself. The weaker expression of D might be cau sed by factors involved in the Rh-related complex or by an as yet unid entified suppressor gene. This study supports the concept that weak D phenotypes carry complete D polypeptides and reflect a quantitative ra ther than a qualitative variation of D.