T-cell transcriptome analysis points up a thymic disorder in idiopathic nephrotic syndrome

Background. Idiopathic nephrotic syndrome is a proteinuric disease secondary to the release of a nonidentified circulating glomerular permeability factor by T cells. Because specificities of T-cell activation in idiopathic nephrotic syndrome remain unknown, we evaluated transcriptional activation of T cells in nephrotic patients during proteinuria. Methods. Transcriptomes of CD2+ cells were analyzed by serial analyis of gene expression (SAGE) in a nephrotic child during proteinuria relapse and after remission, away from any immunosuppressive treatment. Expression of specific transcripts overexpressed during proteinuria relapse was compared by reverse transcription-polymerase chain reaction (RT-PCR) in CD2+ cells from 11 nephrotic patients during relapse and remission and 11 nonnephrotic patients during infection and after recovery. Results. Differential analysis of CD2+ cell transcriptome identified >200 mRNA tags overexpressed during proteinuria relapse, including many T-cell markers. RT-PCR analysis of expression of specific transcripts indicated that (l) under remission conditions, nephrotic children displayed induction of four transcripts, including IKBKB, and repression of NFKBIA as compared to nonnephrotic children after recovery, and (2) proteinuria relapse was associated with induction of L-selectin and T-lymphocyte maturation-associated protein, two markers of T-cell differentiation and recent emigrant/naive T cells. Conclusion. Results indicate that circulating T cells from relapsing nephrotic patients include a significant population of low-mature cells while those from nephrotic patients in remission are characterized by constitutive activation of nuclear factor-kappa B (NF-kappa B), altogether suggesting a thymic dysregulation of apoptosis in nephrotic patients.