An acute model for IgA-mediated glomerular inflammation in rats induced by monoclonal polymeric rat IgA antibodies.
An acute model for IgA-mediated glomerular inflammation in rats was induced by the in situ deposition of IgA directly into the glomerular mesangium. F(ab')2 anti-Thy1 MoAb was used to anchor an antigen, DNP (2,4-dinitrophenol), in the glomeruli of rats. Subsequent infusion of rat polymeric (p-) or monomeric (m-) IgA MoAb with specificity for DNP resulted in mesangial deposition of IgA in both groups of rats. However, acute proteinuria was observed only in p-IgA-treated rats and not in PBS- or m-IgA-treated rats. Immunofluorescence analysis revealed deposition of C3 in an identical pattern to that of IgA in the glomeruli of p-IgA-treated rats. No mesangial deposits of C4 or C1q were seen in these animals. Rats receiving m-IgA or PBS displayed no detectable C3, C4 or C1q deposition. The amount of proteinuria in p-IgA-treated rats was related to the amount of deposited C3. The presence of intraglomerular monocytes was only observed 2 days after p-IgA injection. By light microscopy, aneurysm formation, mesangial hypercellularity and matrix expansion were seen only in p-IgA-treated rats. However, by 37 days post-injection complete resolution of the lesions was observed. No histological renal changes were observed in PBS- or m-IgA-treated rats. In conclusion, an acute form of IgA-mediated nephritis in rats was induced by p-IgA but not by m-IgA. This reproducible model provides a basis for further study into the mechanisms of IgA-mediated glomerular inflammation.
Stad
R K
RK
Department of Nephrology, University Hospital Leiden, The Netherlands.
Bruijn
J A
JA
van Gijlswijk-Janssen
D J
DJ
van Es
L A
LA
Daha
M R
MR
D019297:2,4-Dinitrophenol; D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology; D015941:Complement Hemolytic Activity Assay; D003165:Complement System Proteins / Q000276:immunology; D004140:Dinitrophenols / Q000276:immunology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000276:immunology; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000473:pathology; D006417:Hematuria / Q000473:pathology; D007070:Immunoglobulin A; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D011108:Polymers; D011507:Proteinuria / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D004140:Dinitrophenols; D007070:Immunoglobulin A; D008562:Membrane Glycoproteins; D011108:Polymers; D018800:Thy-1 Antigens; D003165:Complement System Proteins; D019297:2,4-Dinitrophenol