Dynamic nature of maternal multiple RBC alloantibodies after vaccination: Case report and immunological mechanisms review.

Red blood cell (RBC) alloimmunization in pregnancy remains a major cause of hemolytic disease of the fetus and newborn (HDFN). Multiple maternal alloantibodies are uncommon and present significant diagnostic, and transfusion challenges. We report a case of a 35-year-old gravida, with anti-D, anti-C, anti-Fya, and anti-M alloantibodies detected at 10 weeks gestation. Initial titers of anti-D and anti-C were low and stable under serial monitoring. Non-invasive fetal genotyping confirmed an RHD-positive fetus. Following routine maternal vaccination against influenza (28 weeks), pertussis (30 weeks), and RSV (32 weeks), a rapid rise in anti-D and anti-C titers was observed at 31-32 weeks, accompanied by increased serologic reactivity of anti-Fya and anti-M. Middle cerebral artery peak systolic velocity (MCA-PSV) rose to 1.7 MoM, indicating fetal anemia. Two intrauterine transfusions with antigen-negative RBCs were performed. The patient delivered at 37 weeks. The neonate required phototherapy, IVIG, and transfusion support but had a favorable outcome. The temporal association between vaccination and antibody escalation raised the question of immune modulation. Although molecular mimicry is unlikely, non-specific polyclonal immune activation with bystander stimulation of memory B cells may represent a biologically plausible mechanism. However, causality cannot be established. This case highlights the dynamic nature of multiple maternal alloimmunizations, the critical role of serial monitoring and logistical challenges of providing antigen-negative blood for IUT.