I Got It from My Mamma: Sensitization by Transplacental Transfer of Maternal HLA Antibodies Managed with Manual Exchange Transfusion

Abstract

<h3>Introduction</h3> During pregnancy antibodies are passed from mother to fetus with many known immunologic benefits. There is no data about the implications of this on pediatric transplant immunology. We report a case of transplacental transfer of maternal Human Leukocyte Antigen (HLA) antibodies affecting cardiac transplant candidacy in an infant with cardiomyopathy. <h3>Case Report</h3> A 3-week-old Amish boy with a homozygous MYBPC3 mutation causing severe cardiomyopathy admitted for refractory heart failure symptoms was referred for heart transplant evaluation. Labs were notable for high levels of high Mean Fluorescence Intensity (MFI) HLA antibodies (Panel of Reactive Antibodies (PRA) Class I: 74%, Class II: 80%) with no known sensitizing events. Maternal history was remarkable for multiple miscarriages raising the question that his HLA antibodies could be a result of maternal HLA sensitization with transplacental antibody transfer versus active antibody production by the child. Subsequent antibody testing of his mother's blood and breast milk revealed nearly identical HLA antibody profiles to that of the patient. Given the patient's prohibitively small size for antibody removal by plasmapheresis, we elected to perform double volume whole blood exchange transfusions with serial monitoring of his HLA antibodies. Considering his severe ventricular dysfunction, exchange transfusions were performed manually via the push pull method over 6 hours. He ultimately underwent 6 exchange transfusions over the course of 7 weeks. Serial antibody testing revealed a progressive decline in all his HLA antibody levels to <3,000 MFI with only mild rebound after each transfusion consistent with tissue redistribution rather than active antibody production. He was successfully transplanted with a negative PRA (Class I: 0%, Class II: 0%) without post-transplant complications. <h3>Summary</h3> We believe this is the first report demonstrating transplacental acquisition of maternal HLA antibodies in an infant successfully removed via serial whole blood exchange transfusions enabling successful cardiac transplantation.