A transcription factor involved in red blood cell (RBC) production, namely GATA1, could participate in rare expressions of RhD antigen, which is commonly seen in hemolytic disease of the fetus and newborn (HDFN) and transfusion reactions, according to a recently published study in Transfusion Medicine and Hemotherapy.
RhD antigen incompatibility is, along with ABO group incompatibility, the most common cause of HDFN. Mothers without this antigen (RhD-) carrying a fetus with RhD positivity (RhD+) usually require RhD immunoglobulin (RhDIg) administration during and after pregnancy to prevent HDFN in a subsequent pregnancy.
Learn more about HDFN causes and risk factors
There are genetic variants in which some individuals express so small quantities of RhD antigen in their RBCs that they are wrongly classified as RhD—after routine blood typing. A lot of research has been done on this subject, revealing that some patients with so-called weak RhD could be safely considered RhD+, avoiding unnecessary RhDIg administration, while others must be classified as RhD—depending on genetic testing.
The authors of this study have used bioinformatics to explore why some individuals exhibit weak or absent RhD blood group antigens despite having normal RHD gene exons. This research could significantly impact blood typing and transfusion practices. Most cases of weak RhD involve variants in non-coding regions of the RHD gene, which influence gene expression.
“In this study, we aimed to investigate a cohort of weakened D and routinely typed D– samples with normal RHD exons (after routine reference laboratory analysis) for potential disruptions in GATA1 motif candidates,” the authors wrote.
The study focused on GATA1, a transcription factor known to play a role in blood cell differentiation. Results showed that five GATA1 motifs were present in the RHD gene’s regulatory regions. Furthermore, some samples have modifications that differ from standard GATA1 motifs.
“The candidate GATA1 motifs from this study may be useful in future investigations of weak D samples with normal RHD exons,” the authors concluded.
