title: Inhibition of erythroid progenitor cells by anti-Kell antibodies in fetal alloimmune anemia.
abstract: BACKGROUND
  In alloimmune anemia of the newborn, the level of hemolysis caused by the presence of antibodies to antigens of the Kell blood-group system is less than that caused by antibodies to the D antigen of the Rh blood-group system, and the numbers of reticulocytes and normoblasts in the baby's circulation are inappropriately low for the degree of anemia. These findings suggest that sensitization to Kell antigens results in suppression of fetal erythropoiesis as well as hemolysis.
  
  
  METHODS
  We compared the growth in vitro of Kell-positive and Kell-negative hematopoietic progenitor cells from cord blood in the presence of human monoclonal anti-Kell antibodies and anti-D antibodies and serum from women with anti-Kell antibodies.
  
  
  RESULTS
  The growth of Kell-positive erythroid progenitor cells (erythroid burst-forming units and colony-forming units) from cord blood was markedly inhibited by monoclonal IgG and IgM anti-Kell antibodies in a dose-dependent fashion (range of concentrations, 0.2 to 20 percent), but monoclonal anti-D antibodies had no effect. The growth of these types of cells from Kell-negative cord blood was not affected by either type of antibody. Neither monoclonal anti-Kell antibodies nor monoclonal anti-D antibodies inhibited the growth of granulocyte or megakaryocyte progenitor cells from cord blood. Serum from 22 women with anti-Kell antibodies inhibited the growth of Kell-positive erythroid burst-forming units and colony-forming units but not of Kell-negative erythroid burst-forming units and colony-forming units (P<0.001 for the difference between groups). The maternal anti-Kell antibodies had no inhibitory effects on granulocyte-macrophage or mega-karyocyte progenitor cells from cord blood.
  
  
  CONCLUSIONS
  Anti-Kell antibodies specifically inhibit the growth of Kell-positive erythroid burst-forming units and colony-forming units, a finding that supports the hypothesis that these antibodies cause fetal anemia by suppressing erythropoiesis at the progenitor-cell level.
authors.affiliation: Department of Obstetrics, Institute of Obstetrics and Gynaecology, Queen Charlotte's Hospital, London, United Kingdom.
authors.forename: J I
authors.initials: JI
authors.lastname: Vaughan
authors.forename: M
authors.initials: M
authors.lastname: Manning
authors.forename: R M
authors.initials: RM
authors.lastname: Warwick
authors.forename: E A
authors.initials: EA
authors.lastname: Letsky
authors.forename: N A
authors.initials: NA
authors.lastname: Murray
authors.forename: I A
authors.initials: IA
authors.lastname: Roberts
mesh_terms: D000744:Anemia, Hemolytic, Autoimmune; D000911:Antibodies, Monoclonal / Q000502:physiology; D002455:Cell Division / Q000276:immunology; D004899:Erythroblastosis, Fetal / Q000097:blood / Q000209:etiology* / Q000276:immunology; D015672:Erythroid Precursor Cells / Q000276:immunology / Q000502:physiology*; D004920:Erythropoiesis / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D007518:Isoantibodies / Q000502:physiology*; D007626:Kell Blood-Group System / Q000276:immunology*; D011247:Pregnancy; D012204:Rh-Hr Blood-Group System / Q000276:immunology; D012720:Severity of Illness Index
chemical_list: D000911:Antibodies, Monoclonal; D007518:Isoantibodies; D007626:Kell Blood-Group System; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen