Cell Biology – Immunology – Pathology
Kidney International (2005) 67, 2168–2177; doi:10.1111/j.1523-1755.2005.00322.x
T-cell transcriptome analysis points up a thymic disorder in idiopathic nephrotic syndrome
HICHAM MANSOUR, LYDIE CHEVAL, JEAN-MARC ELALOUF, JEAN-CHRISTOPHE AUDE, MARIA-ALEXANDRA ALYANAKIAN, BÉATRICE MOUGENOT, ALAIN DOUCET and GEORGES DESCHÊNES
Institut des Cordeliers, CNRS-UPMC UMR7134, Paris, France; CEA Saclay, Gif sur Yvette., France; INSERM U580, Faculté Necker Enfants Malades, Paris, France; Service d'Anatomie Pathologique, Hôpital Tenon, Paris, France; and Service de Néphrologie Pédiatrique, Hôpital Armand Trousseau, Paris, France
Correspondence: Alain Doucet, UMR 7134, Institut des CordeliersM, 15 rue de l'école de médecine, 75270 Paris cedex 6, France. E-mail:alain.doucet@bhdc.jussieu.fr
Received 21 September 2004; Revised 12 November 2004; Re-revised 13 December 2004; Accepted 20 December 2004.
Abstract
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 (1) 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-
B (NF-B), altogether suggesting a thymic dysregulation of apoptosis in nephrotic patients.
Keywords:
steroid-sensitive nephrotic syndrome, selection, apoptosis, L-selectin, NFB, T-cell differentiation protein
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
Monoclonal antibodies for podocytopathies: rationale and clinical responses
Nature Reviews Nephrology Review (01 Jun 2009)
RESEARCH
A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome
Kidney International Original Article
A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome
Kidney International Original Article
Conservative versus immunosuppressive treatment of patients with idiopathic membranous nephropathy 1
Kidney International Original Article
Kidney International Original Article
