CD4-positive cells from patients with IgA nephropathy demonstrate increased mRNA of cytokines that induce the IgA switch and differentiation

Abstract

IgA nephropathy (IgAN) is characterized by raised serum IgA1 and mesangial IgA1 deposits. We have previously shown increased T-cell activation in IgAN. Recently, transforming growth factor-β (TGF-β) has been shown to induce IgA isotype switch at a clonal level and interleukin 5 (IL5) promotes differentiation into IgA-bearing B cells. In the present study we have examined the TGF-β and IL5 mRNA expression by mitogen-activated CD4-positive T cells from patients with IgAN (n = 25), patients with other primary nephritides (CGN) (n = 24), and healthy control subjects (n = 25). The cytokine genes were analysed by reverse transcription (RT)-polymerase chain reaction (PCR) and were semi-quantitated by normalizing the differences occurring during RT and PCR using a housekeeping gene, β-actin. CDC-positive T cells from IgA nephritic patients expressed a higher level of IL5 mRNA than healthy controls (P < 0.01) and patients with CGN (P < 0.005). CD4-positive T cells from IgA nephritic patients expressed a higher level of TGF-β mRNA than healthy controls (P < 0.01) but no difference was demonstrated on comparison with CGN patients. Elevated TGF-β mRNA expression in patients with CGN probably reflects its other important function as a 'sclerogenic' factor involved in the glomerulosclerosis found in these nephritides. Our data suggest that there is increased expression of cytokine genes which induce the IgA isotype switch and differentiation; these immunological abnormalities may be important in the pathogenesis of IgAN.