Igm and Iga Anti-erythrocyte Autoantibodies Induce Anemia in a Mouse Model Through Multivalency-dependent Hemagglutination but Not Through Complement Activation.
From: Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Blood
- Publish Date: Jun 2007
- ISSN: 0006-4971
- Volume: 109
- Issue: 12
- Pages: 5355-62
- Medium: Print
- Language: English
- Citation (JAMA): Baudino Lucie, Fossati-Jimack Liliane, Chevalley Christelle, et al. Igm and Iga Anti-erythrocyte Autoantibodies Induce Anemia in a Mouse Model Through Multivalency-dependent Hemagglutination but Not Through Complement Activation.. Blood Jun 2007;109:5355-62
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.
Mesh Headings (Keywords): Anemia, Animals, Autoantibodies, Complement Activation, Complement C3, Disease Models, Animal, Erythrocytes, Hemagglutination, Immunoglobulin A, Immunoglobulin M, Mice, Mice, Knockout, Polymers
Check for Full Text / PubMed Unique Identifier (PMID): 17317854
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