Induction of microhematuria by an IgA isotype switch variant of a monoclonal anti-Thy-1.1 antibody in the rat.
IgA nephropathy (IgAN) is a chronic form of glomerulonephritis (GN) characterized by the deposition in the glomerular mesangium of mainly IgA. An experimental form of mesangial proliferative GN can be induced in rats by either polyclonal or monoclonal antibodies against Thy-1.1, a glycoprotein present on the surface of MC. The IgG-mediated renal inflammation is complement dependent and associated with influx of platelets and monocytes. In the present study we switched an IgG2a anti-Thy-1.1 (ER4G) producing hybridoma to an IgA anti-Thy-1.1 (ER4A) producing clone and analyzed the effects of IgA anti-Thy-1.1 in rats. FPLC analysis by gel filtration revealed that the IgA produced by the hybridoma cells was mainly dimeric and polymeric. Infusion of rats with purified ER4A (1 mg/kg) resulted in the deposition of IgA in a mesangial pattern in the glomeruli, similar to that found with ER4G. While administration of ER4G resulted in proteinuria, no significant urinary protein excretion was found in rats treated with ER4A. However, significant microhematuria was observed in rats receiving either ER4A or ER4G. Furthermore, the administration of ER4A was not accompanied by activation of complement, and no significant influx of monocytes or polymorphonuclear leukocytes was observed in contrast to the rats receiving ER4G. We conclude that microhematuria is selectively induced in Wistar rats by mouse IgA anti-Thy-1.1 without detectable complement-mediated injury to MC. These studies may be of importance in understanding the mechanisms leading to IgAN in patients.
Department of Nephrology and Pathology, University Hospital Leiden, University of Leiden, The Netherlands.
M G
MG
van Dixhoorn
A
A
Gorter
T
T
Sato
A M
AM
van der Wal
J D
JD
van Eendenburg
J
J
Rozing
M R
MR
Daha
E
E
de Heer
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002478:Cells, Cultured; D003172:Complement C1 / Q000276:immunology; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D006417:Hematuria / Q000503:physiopathology*; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007134:Immunoglobulin Switch Region / Q000276:immunology*; D007249:Inflammation / Q000473:pathology; D051379:Mice; D011507:Proteinuria / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D018800:Thy-1 Antigens / Q000276:immunology*
D000911:Antibodies, Monoclonal; D003172:Complement C1; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018800:Thy-1 Antigens