INCREASED MESSENGER-RNA ENCODING FOR TRANSFORMING FACTOR-BETA IN CD4+CELLS FROM PATIENTS WITH IGA NEPHROPATHY

IgA nephropathy (IgAN) is a mesangial proliferative glomerulonephritis characterized by predominant mesangial IgA deposits. Recently, transf orming growth factor-beta (TGF-beta) is shown to exert widespread effe cts on extracellular matrix by enhancing its accumulation. In an exper imental model of acute mesangial glomerulonephritis TGF-beta appeared to be involved in the process of glomerulosclerosis, and treatment wit h antagonists of TGF-beta prevented the development of glomerulosclero sis. We examined the TGF-beta mRNA expression by mitogen activated CD4 + T cells from 31 patients with IgAN, 25 healthy controls and 10 patie nts with minimal change nephropathy (MCN) or focal glomerulonephritis (FGN) who were comparable in age and sex. The cytokine gene was analyz ed with reverse transcription followed by polymerase chain reaction an d was semiquantitated by normalizing the differences occurring during reverse transcription and polymerase chain reaction using a housekeepi ng gene, beta-actin. CD4+ T cells from IgA nephritic patients expresse d a higher level of TGF-beta mRNA than that of healthy controls or tha t of MCN/FGN [TGF-beta/actin ratio 1.11 (median), range 0.24 to 3.87 v s. 0.88, range 0.2 to 3.83, P = 0.0157 and 0.36 range 0.09 to 1.6, P = 0.006]. When the biopsies were classified into three grades according to the severity of glomerular and interstitial pathology, there were highly significant differences between the TGF-beta mRNA in CD4+ T cel ls from the three groups of IgA nephritic patients (grade 1, 0.52, ran ge 0.24 to 0.79; grade 2, 1.2, range 0.5 to 3.33; grade 3, 2.17, range 1.45 to 3.87]. Furthermore, immunofluorescent reactivity of anti-TGF- beta antibody in the mesangium was associated with the severity of his topathologic grading (P < 0.05). Our data suggest that, in addition to the local synthesis of TGF-beta by mesangial cells, there is increase d TGF-beta gene expression in circulating CD4+ T cells that may also c ontribute to the glomerulosclerosis in IgA nephropathy.