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) and 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 mg of BSA-PC antigen alone. The mice were sacrificed 6 h after the injection. A 6-hour clearance study was performed. The initial phase of elimination of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-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 between mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 and those receiving 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 somewhat 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 showed a significantly less glomerular BSA-PC antigen deposition than those injected with IgA anti-PC/BSA-PC (positive control), as demonstrated by light microscopy, autoradiography, and immunohistochemistry (each p <0.001). It is inferred that the injected IgG anti-T15 could react with the IgA anti-PC in vivo, directly interfering with immune complex formation by the IgA anti-PC and BSA-PC antigen, thereby resulting in diminished glomerular deposition of the BSA-PC antigen. These findings suggest that an anti-idiotype antibody may be protective in the immunopathogenesis of IgA nephropathy, because of its inhibitory effect on glomerular trapping of an antigen.
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