FcgammaRIII (CD16)-deficient mice show IgG isotype-dependent protection to experimental autoimmune hemolytic anemia
| Autor: | D, Meyer, C, Schiller, J, Westermann, S, Izui, W L, Hazenbos, J S, Verbeek, R E, Schmidt, J E, Gessner |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Cytotoxicity
Immunologic Mice Knockout Erythrocytes Immunoglobulin G/ immunology Erythrocytes/ immunology Receptors IgG Receptors IgG/ deficiency/genetics/immunology ddc:616.07 Immunoglobulin Isotypes Mice Phagocytosis Immunoglobulin G Immunoglobulin Isotypes/immunology Animals Humans Anemia Hemolytic Autoimmune Autoantibodies/immunology Autoantibodies Anemia Hemolytic Autoimmune/ immunology |
| Zdroj: | Blood, Vol. 92, No 11 (1998) pp. 3997-4002 |
| ISSN: | 0006-4971 |
| Popis: | In autoimmune hemolytic anemia (AIHA), there is accumulating evidence for an involvement of FcgammaR expressed by phagocytic effector cells, but demonstration of a causal relationship between individual FcgammaRs and IgG isotypes for disease development is lacking. Although the relevance of IgG isotypes to human AIHA is limited, we could show a clear IgG isotype dependency in murine AIHA using pathogenic IgG1 (105-2H) and IgG2a (34-3C) autoreactive anti-red blood cell antibodies in mice defective for FcgammaRIII, and comparing the clinical outcome to those in wild-type mice. FcgammaRIII-deficient mice were completely resistent to the pathogenic effects of 105-2H monoclonal antibody, as shown by a lack of IgG1-mediated erythrophagocytosis in vitro and in vivo. In addition, the IgG2a response by 34-3C induced a less severe but persistent AIHA in FcgammaRIII knock-out mice, as documented by a decrease in hematocrit. Blocking studies indicated that the residual anemic phenotype induced by 34-3C in the absence of FcgammaRIII reflects an activation of FcgammaRI that is normally coexpressed with FcgammaRIII on macrophages. Together these results show that the pathogenesis of AIHA through IgG1-dependent erythrophagocytosis is exclusively mediated by FcgammaRIII and further suggest that FcgammaRI, in addition to FcgammaRIII, contributes to this autoimmune disease when other IgG isotypes such as IgG2a are involved. |
| Databáze: | OpenAIRE |
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