RGD Reference Report - FcgammaRIII (CD16)-deficient mice show IgG isotype-dependent protection to experimental autoimmune hemolytic anemia. - Rat Genome Database

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FcgammaRIII (CD16)-deficient mice show IgG isotype-dependent protection to experimental autoimmune hemolytic anemia.

Authors: Meyer, D  Schiller, C  Westermann, J  Izui, S  Hazenbos, WL  Verbeek, JS  Schmidt, RE  Gessner, JE 
Citation: Meyer D, etal., Blood. 1998 Dec 1;92(11):3997-4002.
RGD ID: 11054970
Pubmed: PMID:9834201   (View Abstract at PubMed)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FCGR2AHumanautoimmune hemolytic anemia  ISOFcgr3 (Mus musculus) RGD 
Fcgr2aRatautoimmune hemolytic anemia  ISOFcgr3 (Mus musculus) RGD 
Fcgr3Mouseautoimmune hemolytic anemia  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fcgr2a  (Fc gamma receptor 2A)

Genes (Mus musculus)
Fcgr3  (Fc receptor, IgG, low affinity III)

Genes (Homo sapiens)
FCGR2A  (Fc gamma receptor IIa)


Additional Information