Novel estimation of histologic activity in human glomerulonephritis by detection of complement component C3 messenger RNA

Background The histologic diagnosis and clinical findings of glomerulonephritis are very important for determining the treatment strategies. Contrary to expectation, some patients with glomerulonephritis get worse and progress into endstage renal disease. Renal deposition of C3 cleavage products are significant in the pathogenesis and development of glomerulonephritis. Recently, some investigators have reported local C3 synthesis in human renal tissue, and have suggested that it contributes to local inflammatory disorders. The purpose of this study was to explore further the clinicopathologic significance of renal C3 mRNA expression. Methods We examined C3 mRNA expression in kidney tissues (2 normal and 18 diseased) by using nonradioactive, in situ hybridization, and compared results with clinicopathologic findings. Results In all diseased kidney specimens, proximal tubules had C3 mRNA-positive cells. In some cases of minimal-change nephrotic syndrome, lupus nephritis, and membranoproliferative glomerulonephritis, C3 mRNA-positive cells were found in the glomerulus. Specimens from patients with lupus nephritis showed C3 mRNA expression not only in in their tubules and glomeruli, but also in invasive, inflammatory cells. However, no signal was observed in the normal kidney specimens Cases with severe nephrotic conditions and/or with tubular injury showed strong expression. Conclusions These data indicate that renal C3 mRNA that could not been detected by routine immunohistologic methods is, in fact, detectable during the active stage of disease. Therefore detection of renal C3 mRNA may give us new information for assessing pathologic activities, and may be an effective means for determining the prognosis of patients with glomerulonephritis.