Severe fetal anemia caused by anti‐Jra: Burst forming unit‐erythroid colony formation inhibition assay suggesting possible erythroid suppression mechanism

Abstract

AbstractBackgroundThe Jr blood group system includes a single, high‐prevalence antigen, Jra, encoded by the ABCG2 gene. The impact of anti‐Jra in pregnancy is variable, ranging from no clinical effect to severe anemia including some fetal deaths. Case reports have postulated that anti‐Jra mediated fetal anemia is poorly hemolytic, suggesting other mechanisms of anemia may be involved.Study Design and MethodsWe describe the case of severe anti‐Jra mediated fetal anemia. At Canadian Blood Services laboratories, maternal anti‐Jra was tested for phagocytic activity via a monocyte monolayer assay (MMA) and erythroid suppression via inhibition of burst forming unit‐erythroid (BFU‐E) colony formation assays. The New York Blood Center sequenced exons 4 and 7 of the ABCG2 gene.Results and DiscussionSequencing of exons 4 and 7 of the ABCG2 gene revealed maternal compound heterozygosity for two nonsense mutations at exon 7 (c.706 C > T and c.784G > T). Fetal sequencing revealed the c.706C > T polymorphism. The MMA showed a borderline phagocytic index (around the cutoff of five for both donor segments tested [5 ± 1 and 7 ± 3]). The BFU‐E colony formation inhibition assay suggested a dose‐dependent inhibition of BFU‐E colony formation with inhibition percentages of 4%, 11%, and 43% at maternal serum concentrations of 2%, 5%, and 10%, respectively. Our findings support the hypothesis that anti‐Jra may impair erythropoiesis leading to clinically significant fetal/neonatal anemia. A referral to maternal fetal medicine is recommended if anti‐Jra is detected in pregnancy, regardless of the titer.