BACKGROUND: IgA nephropathy is one of the most common forms of primary glomerulonephritis in adults. Its pathogenesis is complex. The nature of infiltrating and proliferating cells and of cellular mediators could contribute to the progression of IgA nephropathy towards end-stage renal failure. METHODS: To evaluate this hypothesis, we attempted to quantify the magnitude of intrarenal gene expression of various cytokines (IL-1 beta, TNF-alpha, IL-6, IL-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 immunofluorescence microscopy. Semi-quantitative reverse-transcriptase polymerase chain 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 pathological grading system. The IFN-gamma/IL-10 ratio was higher in patients with renal dysfunction than in those with normal renal function (P=0.0483). Gene transcript levels of proinflammatory cytokines were related to the amount 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 transcript level was related to the severity of tubulointerstitial damage. The levels of gene expression of IL-10 (P=0.009), IFN-gamma (P=0.03), and TNF-alpha (P=0.005) were related to the degree of mesangial matrix expansion and the extent of intrarenal arteriolar changes correlated with the expression of the IL-8 gene transcript (r=0.43, P=0.004). CONCLUSIONS: We propose that Th1/Th2 predominance and the level of proinflammatory cytokines could determine the pathogenetic processes and the severity of the clinical manifestations of IgA nephropathy.
BACKGROUND: IgA nephropathy is one of the most common forms of primary glomerulonephritis in adults. Its pathogenesis is complex. The nature of infiltrating and proliferating cells and of cellular mediators could contribute to the progression of IgA nephropathy towards end-stage renal failure. METHODS: To evaluate this hypothesis, we attempted to quantify the magnitude of intrarenal gene expression of various cytokines (IL-1 beta, TNF-alpha, IL-6, IL-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 immunofluorescence microscopy. Semi-quantitative reverse-transcriptase polymerase chain 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 pathological grading system. The IFN-gamma/IL-10 ratio was higher in patients with renal dysfunction than in those with normal renal function (P=0.0483). Gene transcript levels of proinflammatory cytokines were related to the amount 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 transcript level was related to the severity of tubulointerstitial damage. The levels of gene expression of IL-10 (P=0.009), IFN-gamma (P=0.03), and TNF-alpha (P=0.005) were related to the degree of mesangial matrix expansion and the extent of intrarenal arteriolar changes correlated with the expression of the IL-8 gene transcript (r=0.43, P=0.004). CONCLUSIONS: We propose that Th1/Th2 predominance and the level of proinflammatory cytokines could determine the pathogenetic processes and the severity of the clinical manifestations of IgA nephropathy.
Authors: Roland Schmitt; Anne-Lie Ståhl; Anders I Olin; Ann-Charlotte Kristoffersson; Johan Rebetz; Jan Novak; Gunnar Lindahl; Diana Karpman Journal: J Immunol Date: 2014-05-21 Impact factor: 5.422
Authors: Luigi Bisceglia; Giuseppina Cerullo; Paola Forabosco; Diletta Domenica Torres; Francesco Scolari; Michele Di Perna; Marina Foramitti; Antonio Amoroso; Sara Bertok; Jürgen Floege; Peter Rene Mertens; Klaus Zerres; Efstathios Alexopoulos; Dimitrios Kirmizis; Mazzucco Ermelinda; Leopoldo Zelante; Francesco Paolo Schena Journal: Am J Hum Genet Date: 2006-11-03 Impact factor: 11.025
Authors: Ho Jun Chin; Ki Young Na; Soo Jin Kim; Kook-Hwan Oh; Yon Su Kim; Chun Soo Lim; Suhnggwon Kim; Dong-Wan Chae Journal: J Korean Med Sci Date: 2005-12 Impact factor: 2.153