The mode of action of treatment by IgG of haemolytic anaemia induced by an anti-erythrocyte monoclonal antibody.
In order to gain insight into the mechanisms by which the infusion of IgG can improve some autoimmune diseases, we induced haemolytic anaemia in mice by the injection of anti-erythrocyte MoAbs derived from NZB mice by S. Izui (Geneva). The IgG1 antibody 31-9D induces anaemia by erythrocyte sequestration in the spleen and liver, whereas the IgG2a antibody 34-3C triggers erythrophagocytosis (Shibata et al., Int Immunol 1990. 2:1133). Treatment of mice with pools of either human or mouse IgG clearly attenuated the anaemia induced by 34-3C, but not by 31-9D. Similar protection was obtained with human monoclonal IgGs from myeloma patients. Prior absorption by mouse erythrocytes did not affect the efficacy of the injected IgG. Treatment with Fc fragments also reduced the anaemia. In vitro experiments confirmed that 34-3C, but not 31-9D, triggered erythrocyte phagocytosis by murine macrophages. This process was completely inhibited by addition of polyclonal or myeloma IgG or of human Fc fragments. These results indicate that, in this model of autoimmune pathology, the protective effect of IgG is mediated by its interaction with the macrophage Fc receptors.
Pottier
Y
Y
Unit of Experimental Medicine, Université Catholique de Louvain, Bruxelles, Belgium.
Pierard
I
I
Barclay
A
A
Masson
P L
PL
Coutelier
J P
JP
D000744:Anemia, Hemolytic, Autoimmune / Q000188:drug therapy* / Q000209:etiology* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000494:pharmacology*; D001323:Autoantibodies / Q000097:blood / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G