A newly identified blood variant found predominantly in Indigenous Australians may have important implications for people affected by hemolytic disease of the fetus and newborn (HDFN), according to new research published in Vox Sanguinis.
In a review spanning eight years, researchers at the Australian Red Cross Lifeblood identified 12 people who share the same unusual pattern of genetic changes in the RHD gene, which determines whether someone’s blood type is RhD-positive or RhD-negative. While nearly all Indigenous Australians are D-positive, this newly recognized variant appears to produce a partial D antigen. This subtle difference can cause the body to form antibodies against D-positive red blood cells.
Nine of the 12 people studied developed anti-D antibodies, most during or after pregnancy. In one case, a baby developed severe HDFN after inheriting the variant allele from their father, leading the mother’s immune system to attack the fetus’s red blood cells.
Learn more about HDFN prognosis
The variant includes six consistent single nucleotide variations (c.186G>T, c.410C>T, c.455A>C, c.602C>G, c.604G>A, c.733G>C) and a rearrangement involving exon 9 of a related gene, RHCE. Though standard blood testing classified most individuals as D-positive, their blood’s altered structure likely prevented full expression of the D antigen, prompting immune reactions similar to those seen in D-negative people exposed to D-positive blood.
The researchers say people with this variant should be considered functionally D-negative when receiving blood transfusions or during pregnancy to avoid sensitization and HDFN risk. Because all cases identified so far were in Indigenous Australians, the team recommends raising awareness in this population and considering targeted genetic testing.
“With wider knowledge of the variant, it is anticipated that there will be increased screening in this population, especially in women of childbearing age,” they concluded.
Sign up here to get the latest news, perspectives, and information about HDFN sent directly to your inbox. Registration is free and only takes a minute.
