INHIBITION OF ERYTHROID PROGENITOR CELLS BY ANTI-KELL ANTIBODIES IN FETAL ALLOIMMUNE ANEMIA

Background In alloimmune anemia of the newborn, the level of hemolysis caused by the presence of antibodies to antigens of the Kell blood-gr oup system is less than that caused by antibodies to the D antigen of the Rh blood-group system, and the numbers of reticulocytes and normob lasts 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-nega tive hematopoietic progenitor cells from cord blood in the presence of human monoclonal anti-Kelt antibodies and anti-D antibodies and serum from women with anti-Kell antibodies. Results The growth of Kell-posi tive erythroid progenitor cells (erythroid burst-forming units and col ony-forming units) from cord blood was markedly inhibited by monoclona l IgG and IgM anti-Kell antibodies in a dose-dependent fashion (range of concentrations, 0.2 to 20 percent), but monoclonal anti-D antibodie s had no effect, The growth of these types of cells from Kell-negative cord blood was not affected by either type of antibody. Neither monoc lonal anti-Kelt 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 gro wth of Kelt-positive erythroid burst-forming units and colony-forming units but not of Kell-negative erythroid burst-forming units and colon y-forming units (P<0.001 for the difference between groups). The mater nal anti-Kell antibodies had no inhibitory effects on granulocyte-macr ophage or megakaryocyte 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 s uppressing erythropoiesis at the progenitor-cell level. (C) 1998, Mass achusetts Medical Society.