ANTIIDIOTYPE ANTIBODY DIRECTLY INTERFERES WITH GLOMERULAR IGA IMMUNE-COMPLEX DEPOSITION

Data from both animal and clinical studies suggest that anti-idiotype antibodies deposited in glomeruli may be involved in the pathogenesis of glomerulonephritis, This study was conducted to examine the role of a hybridoma-AB1-2-derived IgG anti-T15 idiotype (IgG anti-T15) in the immunopathogenesis of a short-term experimental IgA nephropathy. BALB /c mice (12/group) were administered intravenously with: (1) an equal mass (1 mg) of T15-hybridoma-derived IgA antiphosphorylcholine (PC) an d PC-conjugated bovine serum albumin (BSA-PC) antigen; (2) 1 mg of IgA anti-PC, 1 mg of BSA-PC antigen, and 3 mg of IgG anti-T15, or (3) 1 m g of BSA-PC antigen alone, The mice were sacrificed 6 h after the inje ction, A 6-hour clearance study was performed, The initial phase of el imination of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgC a nti-T15 or those receiving the antigen alone was significantly faster than that in those receiving IgA anti-PC/BSA-PC (p < 0.001), There was no significant difference in the elimination rate of BSA-PC antigen b etween mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 and those receiv ing BSA-PC antigen alone, The late phases of elimination of the BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgC anti-T15 showed some what similar to those of BSA-PC antigen in mice receiving IgA anti-PC/ BSA-PC, Moreover, mice injected with IgA anti-PC/BSA-PC/IgG anti-T15 s howed a significantly less glomerular BSA-PC antigen deposition than t hose injected with IgA anti-PC/BSA-PC (positive control), as demonstra ted by light microscopy, autoradiography, and immunohistochemistry (ea ch p < 0.001), It is inferred that the injected IgG anti-T15 could rea ct with the IgA anti-PC in vivo, directly interfering with immune comp lex formation by the IgA anti-PC and BSA-PC antigen, thereby resulting in diminished glomerular deposition of the BSA-PC antigen, These find ings suggest that an anti-idiotype antibody may be protective in the i mmunopathogenesis of IgA nephropathy, because of its inhibitory effect on glomerular trapping of an antigen.