title: Clinically significant anti-KEL RBC alloantibodies are transferred by breast milk in a murine model.
abstract: OBJECTIVE
  Fetuses affected by maternal RBC alloantibodies may have prolonged anaemia after birth, leading one to question whether maternal alloantibody transfer may occur outside the placenta. In response to a recent publication describing breast milk transfer of clinically significant amounts of maternal antiplatelet IgA antibodies from mother to nursing infant, we hypothesized that maternal RBC alloantibodies may also be capable of being transferred in breast milk.
  
  
  METHODS
  The presence and clinical significance of breast milk alloantibody transfer were tested through a series of pregnancy, fostering and transfusion experiments, using a murine model in which transgenic RBCs express the human KEL glycoprotein.
  
  
  RESULTS
  Maternal anti-KEL immunoglobulins, induced through transfusion or pregnancy, were detected in the aqueous phase of breast milk. Further, efficient transfer of maternal anti-KEL IgG and IgA to nursing pups was observed in fostering experiments. The breast milk-acquired alloantibodies were clinically significant in wild-type pups in a transfusion setting, binding to 'incompatible' KEL RBCs and leading to premature clearance from the circulation. Although breast milk-acquired alloantibodies also bound to the RBCs of transgenic KEL-positive fostered pups, no anaemia resulted.
  
  
  CONCLUSIONS
  Taking these murine data in combination with recently published human data of maternal antiplatelet IgA antibodies in breast milk leading to sequelae in some infants, it is theoretically possible that maternal anti-RBC IgA alloantibodies may also be transferred in human breast milk and may lead to sequelae in some infants under some circumstances.
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: M
authors.initials: M
authors.lastname: Santhanakrishnan
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA.|VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Tormey
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: P
authors.initials: P
authors.lastname: Natarajan
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA.|Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Hendrickson
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D000906:Antibodies / Q000276:immunology* / Q000378:metabolism; D001803:Blood Transfusion; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008892:Milk / Q000378:metabolism*; D023421:Models, Animal; D011247:Pregnancy; D014886:Weaning
chemical_list: D000906:Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C585978:KEL protein, human; D008666:Metalloendopeptidases
keywords: RBC; alloimmunization; breast milk