Th1/Th2 predominance and proinflammatory cytokines determine the clinicopathological severity of IgA nephropathy

Background. IgA nephropathy is one of the most common forms of primary glom erulonephritis in adults. Its pathogenesis is complex. The nature of infilt rating and proliferating cells and of cellular mediators could contribute t o the progression of IgA nephropathy towards end-stage renal failure. Methods. To evaluate this hypothesis, we attempted to quantify the magnitud e of intrarenal gene expression of various cytokines (IL-1 beta, TNF-alpha, IL-6, 1L-15, IL-2, IFN-gamma, IL-10) and chemokines (IL-8, RANTES, MCP-1) in 48 renal core biopsy specimens, diagnosed as IgA nephropathy by immunofl uorescence microscopy. Semi-quantitative reverse-transcriptase polymerase c hain reaction using internal competitors was used for the quantification of gene transcripts. Results. The expression of intrarenal gene transcripts of various cytokines and chemokines was closely interrelated, but not associated with the patho logical grading system. The IFN-gamma /IL-10 ratio was higher in patients w ith renal dysfunction than in those with normal renal function (P=0.0483). Gene transcript levels of proinflammatory cytokines were related to the amo unt of proteinuria. In patients with severe glomerular sclerosis, the ratio of IFN-gamma /IL-10 gene transcripts was high (P=0.04). IL-10 gene transcr ipt level was related to the severity of tubulointerstitial damage. The lev els of gene expression of IL-10 (P= 0.009), IFN-gamma (P=0.03), and TNF-alp ha (P=0.005) were related to the degree of mesangial matrix expansion and t he extent of intrarenal arteriolar changes correlated with the expression o f the IL-8 gene transcript (r = 0.33, P = 0.004). Conclusions. We propose that Th1/Th2 predominance and the level of proinfla mmatory cytokines could determine the pathogenetic processes and the severi ty of the clinical manifestations of IgA nephropathy.