EFFECT OF MIZORIBINE ON GLOMERULONEPHRITIS OF EARLY-STAGE IGA NEPHROPATHY IN DDY MICE

Immunopathological studies were performed to determine whether the glo merular injuries in ddY mice, a model for IgA nephropathy (Berger's di sease), are influenced by treatment with mizoribine, a new immunosuppr essive agent. The ddY mice were treated with a low (0.05 mg/ml) or a h igh (0.1 mg/ml) dose of mizoribine for 35 weeks. Flow cytometry analys is showed that there was a marked decrease in the number of B cells an d IgA-bearing B cells. In immunofluorescence, the deposition of IgA in the glomerular mesangial areas and capillary walls of the high-dose m izoribine-treated ddY mice was markedly decreased as compared with tha t of control ddY mice receiving drinking water. The glomerular mesangi al expansion in the high-dose mizoribine-treated ddY mice was milder t han that found in the control ddY mice. In 45-week-old ddY mice, the a verage number of intraglomerular cells in the high-dose and low-dose m izoribine-treated ddY mice was slightly lower than that in drinking wa ter treated ddY mice. The levels of urinary protein excretion in the h igh-dose mizoribine-treated ddY mice were also lower than those in the low-dose mizoribine-treated or drinking water treated ddY mice. It ap pears that treatment of mizoribine might influence the proliferation o f B cells, especially IgA-bearing B cells, and improve the glomerular IgA deposition and glomerular expansion in early-stage IgA nephropathy of ddY mice.