Gene expression profiling of peripheral blood mononuclear cells from patients with minimal change nephrotic syndrome by cDNA microarrays.

BACKGROUND:It is hypothesized that minimal change nephrotic syndrome (MCNS) is a consequence of immune cell dysfunction that may lead to release of glomerular permeability factors. However, the nature of such factors remains uncertain. METHODS:Using cDNA microarrays, we performed gene expression profiling of peripheral blood mononuclear cells (PBMC) from 2 MCNS patients during nephrosis and remission phases. To confirm the cDNA microarray results, we performed quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses in nephrosis and remission samples from 24 MCNS patients and 10 patients with membranous nephropathy (MN), and from 24 healthy subjects. RESULTS:Out of 24,446 genes screened, 171 functionally known genes were up-regulated (at least 2-fold) in PBMC from MCNS patients during the nephrosis phase. 21 genes encoded proteins involved in signal transduction and cytokine response. For further examination, we selected two genes encoding provable secretory proteins, chemokine (C-C) ligand 13 (CCL13) and a novel galectin-related protein (HSPC159). The results of quantitative RT-PCR showed that expressions of CCL13 and HSPC159 mRNA in nephrosis PBMC samples were higher than those in remission samples from all 24 MCNS patients examined, while these mRNA expression patterns were variable among 10 MN patients. CCL13 and HSPC159 mRNA expressions in PBMC from MCNS patients in nephrosis were significantly higher than those in nephrotic MN patients and healthy controls. CONCLUSION:We found that CCL13 and HSPC159 mRNA expressions in PBMC are up-regulated specifically in MCNS patients during the nephrosis phase. Further studies are necessary to clarify whether these expression changes are directly involved in the pathophysiologic processes of MCNS.

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