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) ch aracterized by the deposition in the glomerular mesangium of mainly Ig A. An experimental form of mesangial proliferative GN can be induced i n rats by either polyclonal or monoclonal antibodies against Thy-1.1, a glycoprotein present on the surface of MC. The IgG-mediatrd renal in flammation is complement dependent and associated with influx of plate lets 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) producin g clone and analyzed the effects of IgA anti-Thy-1.1 in rats. FPLC ana lysis by gel filtration revealed that the IgA produced by the hybridom a cells was mainly dimeric and polymeric. Infusion of rats with purifi ed ER4A (1 mg/kg) resulted in the deposition of IgA in a mesangial pat tern in the glomeruli, similar to that found with ER4G. While administ ration of ER4G resulted in proteinuria no significant urinary protein excretion was found in rats treated with ER4A. However, significant mi crohematuria was observed in rats receiving either ER4A or ER4G. Furth ermore, the administration of ER4A was not accompanied by activation o f complement, and no significant influx of monocytes or polymorphonucl ear 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 mechani sms leading to IgAN in patients.