Experimental murine IgA nephropathy following passive administration of vomitoxin-induced IgA monoclonal antibodies.
Oral exposure of mice to vomitoxin (VT) induces elevated levels of serum IgA, circulating IgA immune complexes (IgA-IC), mesangial IgA deposition and haematuria, which all mimic the clinical signs of human IgA nephropathy (IgAN). To further assess the effects of VT-induced IgA in the murine model, B6C3F1 and BALB/C mice were injected intraperitoneally with affinity-purified monoclonal IgA derived from Peyer's patch hybridomas of VT-exposed mice. In B6C3F1 mice, serum IgA, IgM and IgA-IC levels were increased two- to fivefold in treatment groups after 4 and 6 wk compared with controls, whereas increases in serum IgG as high as 18-fold were observed. Urinary erythrocyte counts were also significantly elevated in treatment groups after 2, 4 and 6 wk compared with controls. Concurrent increases in IgA and IgG complexes containing casein, the dietary protein source, occurred in treatment mice. Mesangial IgA, IgG, IgM and C3 deposition were significantly increased in all treatment mice after 6 wk. Electron-dense deposits occurred in the glomeruli of IgA-injected mice after 6 wk. All the above parameters were similarly affected in BALB/C mice. Injection of IgA-secreting hybridoma cells into BALB/C mice increased serum IgA, IgA-IC and IgG levels as well as elevated mesangial IgA, IgG and C3 deposition and haematuria after 2-3 weeks compared with controls. In total, these data indicate that passive administration of VT-induced IgAs can induce the hallmarks of IgA nephropathy. Casein, an antigen found in the diet used for these mice, appeared to form IC with IgA or IgG and these IC may participate in the pathogenesis of this nephropathy.
Yan
D
D
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824, USA.
Rumbeiha
W K
WK
Pestka
J J
JJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D000936:Antigen-Antibody Complex / Q000097:blood; D002364:Caseins / Q000276:immunology; D003176:Complement C3 / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004906:Erythrocyte Count; D005920:Glomerular Mesangium / Q000276:immunology / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000473:pathology; D006417:Hematuria / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007116:Immunization, Passive; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D014255:Trichothecenes / Q000276:immunology / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D002364:Caseins; D003176:Complement C3; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014255:Trichothecenes; C007262:deoxynivalenol