Prevention of murine cryoglobulinemia and associated pathology by monoclonal anti-idiotypic antibody.
A murine IgG3 mAb, clone 6-19, derived from non-manipulated autoimmune MRL/MpJ-lpr/lpr mice is a rheumatoid factor specific for IgG2a and is able to generate cryoglobulins via nonspecific IgG3 Fc-Fc interaction. Intraperitoneal passive transfer of ascites containing the 6-19 mAb into BALB/c mice induces, within 18 h, remarkable pathology characterized by skin vasculitis and acute glomerulonephritis associated with cryoglobulinemia. In order to evaluate the possibility of modulating the development of tissue lesions by an anti-Id antibody, we have raised an IgG2b anti-Id mAb specific to the 6-19 mAb. The cryoprecipitation of 6-19 mAb was completely inhibited in the presence of excess amounts of anti-Id mAb in vitro. In vivo, pretreatment of BALB/c mice with anti-6-19 anti-Id mAb inhibited development of skin vasculitis and glomerulonephritis induced by the 6-19 mAb. The cryoglobulin formation was markedly diminished due to enhanced elimination of the 6-19 mAb from the circulation. In contrast, pretreatment with an IgM anti-IgG3 rheumatoid factor mAb neither protected nor aggravated the development of tissue lesions. These results suggest possible implications in the anti-Id treatment of similar vascular diseases in man.
Spertini
F
F
Department of Pathology, University of Geneva, Switzerland.
Donati
Y
Y
Welle
I
I
Izui
S
S
Lambert
P H
PH
D000276:Adjuvants, Immunologic / Q000502:physiology / Q000627:therapeutic use; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000502:physiology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000502:physiology / Q000627:therapeutic use*; D003449:Cryoglobulinemia / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003450:Cryoglobulins / Q000378:metabolism; D005921:Glomerulonephritis / Q000473:pathology; D007074:Immunoglobulin G / Q000502:physiology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011233:Precipitin Tests; D012217:Rheumatoid Factor / Q000502:physiology; D012867:Skin / Q000473:pathology
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D003450:Cryoglobulins; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D012217:Rheumatoid Factor