Anti-Rh17 antibodiesAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens., a rare immune response linked to hemolytic disease of the fetus and newborn (HDFN), can endanger pregnancies when mothers have the uncommon D–/D– RhRh factor A protein or antigen found on red blood cells. When an Rh-negative mother carries an Rh-positive fetus, her immune system may make antibodies that attack the fetus' red blood cells. phenotype, as described in a case report published recently in Transfusion and Apheresis Science.
HDFN occurs when a woman lacks several common Rh blood groupBlood group A classification of blood based on inherited markers found on red blood cells. The ABO and Rh blood groups are most common in HDFN. antigensAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens. and has been exposed to typical Rh-positiveRh-Positive A blood type trait that means your red blood cells have the Rh(D) antigen. blood through pregnancy or transfusion. Once sensitizedSensitization The process by which a mother’s immune system becomes “primed” to recognize and attack fetal red blood cells carrying incompatible antigens., the immune system can attack a baby’s red blood cells, causing severe anemiaAnemia A condition that occurs when the body doesn’t have enough healthy red blood cells to carry oxygen to its tissues. In HDFN, anemia occurs when maternal antibodies destroy fetal red blood cells. and jaundiceJaundice A common symptom of HDFN, jaundice is caused by excess bilirubin and is characterized by a yellow tint to the skin or eyes. that may require urgent blood transfusion.
One such case involved a mother with the D–/D– phenotype whose newborn developed anemia and dangerously high levels of bilirubinBilirubin A yellow substance produced when red blood cells break down. High bilirubin levels in newborns with HDFN can cause jaundice or, in severe cases, brain damage. shortly after birth. The baby required an exchange transfusion using blood sourced from Iran’s rare blood bank, as compatible donors are exceptionally scarce, estimated at only one in every 100,000 people worldwide. Without such a transfusion, the newborn’s life would have been at risk.
“Although our study faced limitations in terms of time and financial resources, preventing extensive molecular investigations, future research could explore the samples from this study to ascertain the presence of a chimeric gene or a potential new allele,” explained the authors of this case report.
Read more about symptoms and risks for HDFN
Testing revealed the mother’s blood group was O+ but lacked the C, E, c, and e antigens, confirming the D–/D– phenotype. AntibodyAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens. screening showed strong reactivity for Anti-Rh17, while direct antiglobulin testing on the baby’s red cells was negative. The mother’s history included a prior blood transfusion after a road accident, a likely source of her sensitizationSensitization The process by which a mother’s immune system becomes “primed” to recognize and attack fetal red blood cells carrying incompatible antigens..
Following the delivery, researchers screened 13 family members. Four, including the mother, her mother, a sister, and a brother, shared the D–/D– phenotype. Blood from these relatives was stored for potential future use, both for themselves and for others in urgent need. Genetic testing confirmed all four lacked the RHCE gene, which normally produces the C, E, c, and e antigens.
The Rh blood group system is second only to ABO in its importance for transfusion compatibility and pregnancy care. While most people carry multiple Rh antigens, those without them face higher risks if exposed to mismatched blood. For patients and expectant mothers with the D–/D– phenotype, early blood typing, antibody screening, and rare donor identification can mean the difference between life and death in the event of HDFN.
For people living with this rare blood type, awareness and preparation are key. Storing compatible blood in advance can protect future pregnancies and ensure rapid treatment during emergencies.
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.
