SEARCH:   Advanced

Blood, 1 August 2005, Vol. 106, No. 3, pp. 771-772. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Spitalnik, S. L. Search for Related Content PubMed Articles by Spitalnik, S. L. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSFUSION MEDICINE Comment on Zimring et al, page 1105 Yin and yang in transfusion medicine Steven L. Spitalnik COLLEGE OF PHYSICIANS & SURGEONS OF COLUMBIA UNIVERSITY A new mouse model of transfusion of incompatible RBCs sheds light on the mysterious process of antibody-induced antigen suppression. Antibody binding to red blood cell (RBC) antigens classically results in hemolysis. The converse is the phenomenon of "antigen suppression," which has been described in only a few case reports. These cases typically occurred in patients with autoimmune hemolytic anemia (AIHA) in which the autoantibody led to suppressed expression of its cognate antigen. Suppression was transient with antigen re-expression when the antibody disappeared. In addition, 2 antigens were suppressed sequentially in 1 patient by the appearance and disappearance of autoantibodies with different specificities.1 Antigen suppression occurred most often with antibodies recognizing Kell blood group system antigens, but other specificities were also described. These antibodies can hemolyze autologous and transfused RBCs,2 and antigen suppression protects RBCs from hemolysis. Thus, unraveling the mechanism of antigen suppression may lead to new ways of treating AIHA and preventing transfusion reactions. In this issue of Blood, Zimring and colleagues present a novel mouse model that may provide this understanding. Various mechanisms have been proposed to explain antigen suppression, but it is still not understood. For example, since these antibodies may bind antigens on RBC progenitors, they may prevent antigen synthesis; however, thisdoes not explain antigen suppression of transfused RBCs.2 Antibody binding to the RBC antigen may also interfere with in vitro serological tests to detect that antigen; however, immunoblots of antigen-suppressed RBCs demonstrated the absence of the relevant antigen.1 Finally, the RBC antigen may be destroyed, with circulating microbial enzymes the likely culprits; however, infections in these patients were rarely described. Similarly, Williamson and colleagues postulated the "shedding" of immune complexes containing the relevant RBC antigen and its bound autoantibody.1 Although mice have at least 10 RBC alloantigen systems (ie, Ea1-Ea10 [erythrocyte alloantigens 1-10]), and several mouse strains express transgenic RBC antigens,3 these have not yet been exploited to study incompatible RBC transfusions. To this end, Zimring et al transfused RBCs from transgenic mice expressing a transmembrane form of hen egg lysozyme (HEL) into recipients with high titers of immunoglobulin G (IgG) anti-HEL. Surprisingly, the transfused RBCs were not hemolyzed; rather, HEL was specifically removed from the transfused RBCs, which then survived normally. This Fc receptor–mediated process did not require the spleen and probably occurred in the liver. Given that extravascular hemolysis, and not antigen suppression, is found in both a mouse model of AIHA4 and following transfusion of glycophorin A transgenic mouse RBCs into alloimmunized recipients (David A. Schirmer, Shuh-Chung Song, and S.L.S., unpublished observations, May 2005), it will be interesting to compare and contrast these models in future studies. Finally, the model of Zimring et al is reminiscent of the "transfer reaction" involving immune complexes bound to complement receptor 1 (ie, CR1) on primate RBCs, in which macrophages ingest both the immune complex and CR1 without producing hemolysis.5 In particular, the Fc region of the relevant antibody and intact Fc receptor function are required for the transfer reaction.5,6 In addition, the liver primarily removes the CR1-bound immune complexes in vivo.6 Although mouse RBCs do not express CR1, this process may not be limited to CR1,7 thereby suggesting additional ways of studying antigen suppression in vivo using the mouse model of Zimring et al and in vitro using antibody and RBC samples from human patients. References Williamson LM, Poole J, Redman C, et al. Transient loss of proteins carrying Kell and Lutheran red cell antigens during consecutive relapses of autoimmune thrombocytopenia. Br J Haematol. 1994;87: 805-812.[Medline] [Order article via Infotrieve] Vengelen-Tyler V, Gonzalez B, Garratty G, et al. Acquired loss of red cell Kell antigens. Br J Haematol. 1987;65: 231-234.[Medline] [Order article via Infotrieve] Halverson GR, Chaudhuri A, Huang T, Yazdanbakhsh K, Reid ME. Immunization of transgenic mice for production of MoAbs directed at polymorphic blood group antigens. Transfusion. 2001;41: 1393-1396.[Medline] [Order article via Infotrieve] Izui S, Fossati-Jimack L, da Silveira SA, Moll T. Isotype-dependent pathogenicity of autoantibodies: analysis in experimental autoimmune hemolytic anemia. Springer Semin Immunopathol. 2001;23: 433-445.[CrossRef][Medline] [Order article via Infotrieve] Reinagel ML, Taylor RP. Transfer of immune complexes from erythrocyte CR1 to mouse macrophages. J Immunol. 2000;164: 1977-1985.[Abstract/Free Full Text] Nardin A, Schlimgen R, Holers VM, Taylor RP. A prototype pathogen bound ex vivo to human erythrocyte complement receptor 1 via bispecific monoclonal antibody complexes is cleared to the liver in a mouse model. Eur J Immunol. 1999;29: 1581-1586.[Medline] [Order article via Infotrieve] Craig ML, Waitumbi JN, Taylor RP. Processing of C3b-opsonized immune complexes bound to non-complement receptor 1 (CR1) sites on red cells: phagocytosis, transfer, and associations with CR1. J Immunol. 2005;174: 3059-3066.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Nonhemolytic antibody-induced loss of erythrocyte surface antigen James C. Zimring, Gregory A. Hair, Traci E. Chadwick, Seema S. Deshpande, Kimberly M. Anderson, Christopher D. Hillyer, and John D. Roback Blood 2005 106: 1105-1112. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Spitalnik, S. L. Search for Related Content PubMed Articles by Spitalnik, S. L. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020