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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5355-5362. Prepublished online as a Blood First Edition Paper on February 22, 2007; DOI 10.1182/blood-2006-11-059899. This Article Full Text (PDF) All Versions of this Article: blood-2006-11-059899v1 109/12/5355    most recent 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 Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Baudino, L. Articles by Izui, S. Search for Related Content PubMed PubMed Citation Articles by Baudino, L. Articles by Izui, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 27, 2006 Accepted February 17, 2007 IgM and IgA anti-erythrocyte autoantibodies induce anemia in a mouse model through multivalency-dependent hemagglutination but not through complement activation Lucie Baudino, Liliane Fossati-Jimack, Christelle Chevalley, Eduardo Martinez-Soria, Marc J. Shulman, and Shozo Izui* Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland Rheumatology Section, Imperial College School of Medicine, London, United Kingdom Department of Immunology, University of Toronto, Ontario, Canada * Corresponding author; email: shozo.izui{at}medecine.unige.ch. By generating IgM and IgA switch variants of the 34-3C IgG2a anti-red blood cell (RBC) autoantibody, we evaluated the pathogenic activity of these two isotypes in view of the Fc-associated effector functions, i.e. complement activation and polyvalency-dependent agglutination. We found that polymeric forms of 34-3C IgM and IgA anti-RBC autoantibody were as pathogenic as IgG2a, which was the most pathogenic among four different IgG subclasses, while their monomeric variants completely lacked pathogenic effects. Histological examination showed that 34-3C IgM and IgA autoantibodies caused anemia as a result of multivalency-dependent hemaggultination and subsequent sequestration of RBC in the spleen, in contrast to Fc receptor- and complement receptor-mediated erythrophagocytosis by Kupffer cells with IgG isotypes. In addition, the development of anemia induced by IgM and IgA isotypes of 34-3C antibody and by two additional IgM anti-RBC monoclonal autoantibodies was not inhibited at all in C3-deficient mice, indicating the lack of involvement of complement activation in the pathogenesis of IgM- and IgA-induced anemia. Our data demonstrate a remarkably high pathogenic potential of polymeric forms of IgM and IgA anti-RBC autoantibodies owed to their ability to induce hemagglutination, but completely independent of complement activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. M. Czajkowsky and Z. Shao The human IgM pentamer is a mushroom-shaped molecule with a flexural bias PNAS, September 1, 2009; 106(35): 14960 - 14965. [Abstract] [Full Text] [PDF] P. Borel, M. Benkhoucha, M. S. Weber, S. S. Zamvil, M.-L. Santiago-Raber, and P. H. Lalive Glatiramer acetate treatment does not modify the clinical course of (NZB x BXSB)F1 lupus murine model Int. Immunol., October 1, 2008; 20(10): 1313 - 1319. [Abstract] [Full Text] [PDF] L. Baudino, F. Nimmerjahn, S. Azeredo da Silveira, E. Martinez-Soria, T. Saito, M. Carroll, J. V. Ravetch, J. S. Verbeek, and S. Izui Differential Contribution of Three Activating IgG Fc Receptors (Fc{gamma}RI, Fc{gamma}RIII, and Fc{gamma}RIV) to IgG2a- and IgG2b-Induced Autoimmune Hemolytic Anemia in Mice J. Immunol., February 1, 2008; 180(3): 1948 - 1953. [Abstract] [Full Text] [PDF]

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