title: Anti-idiotype antibody directly interferes with glomerular IgA immune complex deposition.
abstract: 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/IgG 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.
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan/ROC.
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.forename: L F
authors.initials: LF
authors.lastname: Sheu
authors.forename: M F
authors.initials: MF
authors.lastname: Shaio
authors.forename: T H
authors.initials: TH
authors.lastname: Huang
authors.forename: S L
authors.initials: SL
authors.lastname: Ding
authors.forename: W H
authors.initials: WH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology*; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D005260:Female; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D007070:Immunoglobulin A / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010767:Phosphorylcholine / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D000941:Antigens; D007070:Immunoglobulin A; D010767:Phosphorylcholine; D012710:Serum Albumin, Bovine