Anti-Ge3 causes late-onset hemolytic disease of the newborn: The fourth case in three Hispanic families

Hemolytic disease of the fetus and newborn (HDFN) is a rare, but significant, cause of neonatal morbidity and mortality. HDFN occurs when a maternal immunoglobulin (Ig)G antibody, directed against an antigen on fetal red blood cells (RBCs), crosses the placenta and attacks fetal RBCs, causing hemolytic anemia. Maternal antibodiesdevelop after exposure to foreign RBC antigens, for example, via blood transfusion or via transplacental fetomaternal hemorrhage. Historically, ABO antibodies have caused the majority of mild cases of HDFN, and D alloimmunizationhas caused the majority of severe cases.1 The prevalence of HDFN associated with anti-D has declined with routine anti-D prophylaxis for all D– women.1 Other antibodies, such as anti-K, anti-c, and anti-E, now cause an increasingly large percentage of severe HDFN cases, although anti-D still causes the majority of them.1,2 IgG antibodies to any of the 300 RBC antigens other than ABO and Rh can also cause HDFN but are much rarer. Many of these antigens (e.g., Lub, Yta, and Vel) are not well developed on fetal RBCs or are of high prevalence so only a small percentage of the population is at risk for making these antibodies. The Gerbich blood group system consists of 11 antigens carried on RBC membrane glycophorins C(GPC) and D (GPD), proteins that help maintain RBC membrane shape and stability.3 Five of the Gerbich antigens (Ge5, Ge6, Ge7, Ge8, Ge9) are of low prevalence and have not been reported to be clinically significant.3 The other six Gerbich antigens (Ge2, Ge3, Ge4, Ge10, Ge11, Ge12) are high-prevalence antigens (found in >99.9% of the population).3 Three Gerbich-negative types have been identified: Ge:–2,3,4 (Yus type); Ge:–2,–3,4 (Gerbich type); and Ge:–2,–3,–4 (Leach type).3 Anti-Ge3 is usually IgG and reacts at the anti-human globulin phase of antibody detection tests, but IgM forms of anti-Ge3 have also been reported.3 Anti-Ge3 can cause autoimmune hemolytic anemiaand alloimmunetransfusion reactions3,4 but was not known to be associated with severe HDFN until recently. Two relatively recent reports described three infants who developed severe, late-onset anemia and hyperbilirubinemia up to 40 days after birth to mothers with anti-Ge3.5,6 We now report a fourth such case.