title: Suppression of in vitro megakaryopoiesis by maternal sera containing anti-HPA-1a antibodies.
abstract: Incompatibility of the human platelet antigen-1 (HPA-1) system is the most common cause of fetal/neonatal alloimmune thrombocytopenia (F/NAIT) and is thought to be mediated by accelerated clearance of antibody-opsonized fetal platelets. We evaluated the effect of maternal sera containing anti-HPA-1a antibodies (F/NAIT sera) on in vitro megakaryopoiesis. Compared with control maternal sera, 14 out of 17 F/NAIT sera significantly reduced megakaryocyte (MK) number. This finding was associated with increased apoptosis and cell death of early MKs/MK progenitors, but normal maturation and differentiation of surviving MKs. An analysis of platelet counts in infants born to mothers following antenatal intravenous immunoglobulin (IVIG) ± prednisone therapy demonstrated a significant and moderately strong correlation between the MK growth in cultures and the infants' platelet counts at birth. These findings suggest that maternal anti-HPA-1a antibodies can suppress fetal megakaryopoiesis by inducing early cell death and that this influences the neonatal platelet count. Thus, the ability of maternal antibodies to suppress MK growth is a potential predictive factor for the fetal response to maternal IVIG therapy.
authors.affiliation: Division of Newborn Medicine, Boston Children's Hospital, Boston, MA;
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Liu
authors.affiliation: Division of Pediatric Hematology-Oncology, New York Presbyterian Hospital, New York, NY;
authors.forename: James B
authors.initials: JB
authors.lastname: Bussel
authors.affiliation: Division of Pediatric Hematology-Oncology, New York Presbyterian Hospital, New York, NY;
authors.forename: Madhavi
authors.initials: M
authors.lastname: Lakkaraja
authors.affiliation: Division of Newborn Medicine, Boston Children's Hospital, Boston, MA; Hematology and Medical Oncology Unit, Hospital Morales-Meseguer, Centro de Hemodonación, Instituto Murciano de Investigacion Biosanitaria, Murcia, Spain;
authors.forename: Francisca
authors.initials: F
authors.lastname: Ferrer-Marin
authors.affiliation: Department of Haematology, University of Cambridge/National Health Service Blood and Transplant, Cambridge, United Kingdom;
authors.forename: Cedric
authors.initials: C
authors.lastname: Ghevaert
authors.affiliation: Clinical Research Center, Boston Children's Hospital, Boston, MA; and.
authors.forename: Henry A
authors.initials: HA
authors.lastname: Feldman
authors.affiliation: Platelet & Neutrophil Immunology Laboratory, Blood Center of Wisconsin, Milwaukee, WI.
authors.forename: Janice G
authors.initials: JG
authors.lastname: McFarland
authors.affiliation: Division of Newborn Medicine, Boston Children's Hospital, Boston, MA;
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Chavda
authors.affiliation: Division of Newborn Medicine, Boston Children's Hospital, Boston, MA;
authors.forename: Martha
authors.initials: M
authors.lastname: Sola-Visner
mesh_terms: D016824:Antigens, Human Platelet / Q000276:immunology*; D005260:Female; D006410:Hematopoiesis / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D039661:Integrin beta3; D008533:Megakaryocytes / Q000276:immunology*; D011247:Pregnancy; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000276:immunology* / Q000503:physiopathology
chemical_list: D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D039661:Integrin beta3