Correspondence

Inhibition of Megakaryopoiesis by Kell-Related Antibodies

N Engl J Med 2000; 343:72July 6, 2000

Article

To the Editor:

Kell, one of the major red-cell groups in humans, comprises 22 antigens. These antigens are encoded by alleles on chromosome 7, including sets of antithetical antigens such as Kell (K) and Cellano (k), which differ by a single amino acid.1 Anti-Kell antibodies have been shown to suppress the growth of erythroid progenitor cells in a semisolid culture system.2 This finding has been linked to the reticulocytopenia that is usual in hemolytic disease of the newborn (erythroblastosis neonatorum) induced by anti-Kell antibodies.3 We recently observed substantial thrombocytopenia in three fetuses with erythroblastosis fetalis due to anti-Kell antibodies (platelet counts, 70 × 10⁹ per liter, 53 × 10⁹ per liter, and 67 × 10⁹ per liter). The mean (±SE) platelet count in these three fetuses was 63±5 × 10⁹ per liter, as compared with a mean platelet count of 252±15 × 10⁹ per liter in five fetuses with erythroblastosis fetalis induced by anti-D antibodies (P<0.005 by the t-test). In these fetuses, intrauterine cord blood was obtained between the 21st and 28th weeks of gestation.4 We therefore studied the expression of Kell blood-group antigens on megakaryocytic progenitor cells from both cord blood and adult blood using a commercial semisolid in vitro culture system (MegaCult-C, Stem Cell Technologies, Vancouver, Canada) that supports the growth of megakaryocyte colony-forming units (CFU-MK). Because of the low frequency of persons with the K+k– phenotype (0.2 percent), we used only K–k+ blood samples.

In five experiments using cord-blood mononuclear cells from healthy K–k+ newborns, we observed a clear and dose-dependent inhibition of the growth of CFU-MK with the addition of 10 μl of human anti-k antibody per dish (titer, 1:64; IgG, Diamed, Basel, Switzerland) (Table 1Table 1Growth of Megakaryocyte Colony-Forming Units Derived from Cord-Blood Mononuclear Cells from K–k+ Newborns in the Presence and Absence of Anti-k and Anti-K Antibodies.). Not unexpectedly, the addition of 10 μl of human anti-K antibody per dish (titer, 1:64; IgG, Diamed) had no effect on the growth of CFU-MK from these K– infants, suggesting specific inhibition by the anti-k antibody (Table 1). Using peripheral-blood mononuclear cells from nine hematologically normal adults, we also found a significant inhibition of the growth of CFU-MK with the addition of 10 μl of anti-k antibody per dish (control value, 8.3±1.5 colonies per dish; value with the addition of anti-k antibody, 3.8±0.7 colonies per dish; P<0.005).

Our findings indicate that Kell blood-group antigens are expressed not only on erythroid progenitors but also on megakaryocyte progenitors. Therefore, antibody-mediated inhibition of progenitor cells may affect not only erythropoiesis in newborns with erythroblastosis neonatorum induced by anti-Kell antibodies, but also the formation of platelets, as we observed in three fetuses.

Thomas Wagner, M.D.
University Hospital, A-8036 Graz, Austria

Gerhard Bernaschek, M.D.
Klaus Geissler, M.D.
University of Vienna, A-1090 Vienna, Austria

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Citing Articles (9)

Citing Articles

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   M. E. A. Rath, V. E. H. J. Smits-Wintjens, D. Oepkes, E. W. van Zwet, I. L. van Kamp, A. Brand, F. J. Walther, E. Lopriore. (2011) Thrombocytopenia at birth in neonates with red cell alloimmune haemolytic disease. Vox Sanguinisno-no
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   E. S. A. van den Akker, F. J. C. M. Klumper, A. Brand, H. H. H. Kanhai, D. Oepkes. (2008) Kell alloimmunization in pregnancy: associated with fetal thrombocytopenia?. Vox Sanguinis 95:1, 66-69
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   Günther F. Körmöczi, Thomas Wagner, Christof Jungbauer, Maria Vadon, Norbert Ahrens, Willi Moll, Annelies Mühlbacher, Seyhan Özgül-Gülce, Thomas Kleinrath, Susanne Kilga-Nogler, Diether Schönitzer, Christoph Gassner. (2007) Genetic diversity of KELnull and KELel: a nationwide Austrian survey. Transfusion 47:4, 703-714
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   Vagner Castro, Hartmut Kroll, Andréa F. Origa, Mônica A. Falconi, Sílvia B.D. Marques, Sérgio T. Marba, Renato Passini, Joyce M. Annichino-Bizzacchi, Fernando F. Costa, Sentot Santoso, Valder R. Arruda. (2007) A prospective study on the prevalence and risk factors for neonatal thrombocytopenia and platelet alloimmunization among 9332 unselected Brazilian newborns. Transfusion 47:1, 59-66
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   Jeffrey J. Pu, Colvin M. Redman, Jan W.M. Visser, Soohee Lee. (2005) Onset of expression of the components of the Kell blood group complex. Transfusion 45:6, 969-974
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6. 6

   P. A. Arndt, G. Garratty, G. Daniels, C. A. Green, A. M. Wilkes, P. Hunt, J. Do, S. Glenn, D. Peterson. (2005) Late onset neonatal anaemia due to maternal anti-Ge: possible association with destruction of eythroid progenitors. Transfusion Medicine 15:2, 125-132
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7. 7

   Thomas Wagner, Bernhard Resch, Friedrich Reiterer, Christoph Gassner, Gerhard Lanzer. (2004) Pancytopenia Due to Suppressed Hematopoiesis in a Case of Fatal Hemolytic Disease of the Newborn Associated With Anti-K Supported by Molecular K1 Typing. Journal of Pediatric Hematology/Oncology 26:1, 13-15
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8. 8

   Yoshiro Koda, Mikiko Soejima, Makoto Tsuneoka, Kiyoshi Yasumoto, Takanori Higashitani, Kimitaka Sagawa, Hiroshi Kimura. (2002) Heterozygosity for two novel null alleles of the KEL gene causes the Kell-null phenotype in a Japanese woman. British Journal of Haematology 117:1, 220-225
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9. 9

   T. Wagner, G. Lanzer, K. Geissler. (2002) Kell Expression on Myeloid Progenitor Cells. Leukemia & Lymphoma 43:3, 479-485
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