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Scientific article
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IgM and IgA anti-erythrocyte autoantibodies induce anemia in a mouse model through multivalency-dependent hemagglutination but not through complement activation

Published inBlood, vol. 109, no. 12, p. 5355-5362
Publication date2007
Abstract

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 2 isotypes in view of the Fc-associated effector functions (ie, 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 4 different IgG subclasses, whereas 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 2 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 due to their ability to induce hemagglutination but completely independent of complement activation.

Keywords
  • Anemia/*etiology/immunology
  • Animals
  • Autoantibodies/*immunology
  • Complement Activation
  • Complement C3/deficiency
  • Disease Models, Animal
  • Erythrocytes/*immunology
  • Hemagglutination/*immunology
  • *Immunoglobulin A
  • *Immunoglobulin M
  • Mice
  • Mice, Knockout
  • Polymers
Affiliation Not a UNIGE publication
Citation (ISO format)
BAUDINO, Lucie Clementine et al. IgM and IgA anti-erythrocyte autoantibodies induce anemia in a mouse model through multivalency-dependent hemagglutination but not through complement activation. In: Blood, 2007, vol. 109, n° 12, p. 5355–5362. doi: 10.1182/blood-2006-11-059899
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ISSN of the journal0006-4971
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