Tran Ann, Yan Matthew T S, Branch Donald R, Blacquiere Megan, Pineault Nicolas, Pasha Roya, Clarke Gwen
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Medical Affairs and Innovation, Canadian Blood Services, Ottawa, Ontario, Canada.
Transfusion. 2023 Apr;63(4):877-882. doi: 10.1111/trf.17265. Epub 2023 Feb 2.
The Jr blood group system includes a single, high-prevalence antigen, Jr , encoded by the ABCG2 gene. The impact of anti-Jr in pregnancy is variable, ranging from no clinical effect to severe anemia including some fetal deaths. Case reports have postulated that anti-Jr mediated fetal anemia is poorly hemolytic, suggesting other mechanisms of anemia may be involved.
We describe the case of severe anti-Jr mediated fetal anemia. At Canadian Blood Services laboratories, maternal anti-Jr 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.
Sequencing 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-Jr may impair erythropoiesis leading to clinically significant fetal/neonatal anemia. A referral to maternal fetal medicine is recommended if anti-Jr is detected in pregnancy, regardless of the titer.
