title: Can antibodies with specificity for soluble antigens mimic the therapeutic effects of intravenous IgG in the treatment of autoimmune disease?
abstract: Intravenous Ig (IVIg) mediates protection from the effects of immune thrombocytopenic purpura (ITP) as well as numerous other autoimmune states; however, the active antibodies within IVIg are unknown. There is some evidence that antibodies specific for a cell-associated antigen on erythrocytes are responsible, at least in part, for the therapeutic effect of IVIg in ITP. Yet whether an IVIg directed to a soluble antigen can likewise be beneficial in ITP or other autoimmune diseases is also unknown. A murine model of ITP was used to determine the effectiveness of IgG specific to soluble antigens in treating immune thrombocytopenic purpura. Mice experimentally treated with soluble OVA + anti-OVA versus mice treated with OVA conjugated to rbcs (OVA-rbcs) + anti-OVA were compared. In both situations, mice were protected from ITP. Both these experimental therapeutic regimes acted in a complement-independent fashion and both also blocked reticuloendothelial function. In contrast to OVA-rbcs + anti-OVA, soluble OVA + anti-OVA (as well as IVIg) did not have any effect on thrombocytopenia in mice lacking the inhibitory receptor FcgammaRIIB (FcgammaRIIB(-/-) mice). Similarly, antibodies reactive with the endogenous soluble antigens albumin and transferrin also ameliorated ITP in an FcgammaRIIB-dependent manner. Finally, broadening the significance of these experiments was the finding that anti-albumin was protective in a K/BxN serum-induced arthritis model. We conclude that IgG antibodies directed to soluble antigens ameliorated 2 disparate IVIg-treatable autoimmune diseases.
authors.affiliation: Transfusion Medicine Research and the Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Vinayakumar
authors.initials: V
authors.lastname: Siragam
authors.forename: Davor
authors.initials: D
authors.lastname: Brinc
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Crow
authors.forename: Seng
authors.initials: S
authors.lastname: Song
authors.forename: John
authors.initials: J
authors.lastname: Freedman
authors.forename: Alan H
authors.initials: AH
authors.lastname: Lazarus
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001168:Arthritis / Q000276:immunology; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use*; D007167:Immunotherapy; D007249:Inflammation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000494:pharmacology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000139:chemically induced / Q000276:immunology* / Q000628:therapy*; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012995:Solubility
chemical_list: D000906:Antibodies; D000941:Antigens; D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG; D010047:Ovalbumin