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  • Title: CD4-positive cells from patients with IgA nephropathy demonstrate increased mRNA of cytokines that induce the IgA switch and differentiation.
    Author: Lai KN, Ho RT, Leung JC, Chui YL, Lim PL, Lui SF, Li PK.
    Journal: J Pathol; 1994 Sep; 174(1):13-22. PubMed ID: 7965399.
    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-beta (TGF-beta) 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-beta 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, beta-actin. CD4-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-beta mRNA than healthy controls (P < 0.01) but no difference was demonstrated on comparison with CGN patients. Elevated TGF-beta 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.
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