[New insights about immunopathology of lipoid nephrosis].
Clinical and experimental observations suggest that Lipoid Nephrosis (Minimal change nephrotic syndrome) results from T cell dysfunction due to still unknown mechanisms. By subtractive screening library, we identified 84 transcripts, of which twelve match with proteins of yet unknown function and thirty are unknown clones. Among the 42 known transcripts, at least 18 are closely involved in the TCR-mediated complex signaling cascade. This includes genes encoding components of the T cell receptor and proteins associated with the cytoskeleton scaffold, as well as transcription factors such as NF-kappa B and c-maf. During the relapse phase, we have found significant alterations of the NF-kappa B/I kappa Ba regulatory pathway, whereas very low levels of IL12R beta 2 mRNA were detected suggesting that T cell activation evolves toward a Th2 phenotype. We have shown that c-maf is highly induced, shuttling between nuclear and cytoplasmic compartment during the relapse and the remission phases, respectively. Contrasting with the nuclear expression of c-maf, low IL4 levels were detected in relapse. This suggests that the downstream target gene of c-maf in Lipoid Nephrosis, is not IL4 and provides new directions in research leading to identify the target gene, possibly an unknown Th2 cytokine, which might play a critical role in the pathophysiology of this disease. Thus, the combination of subtractive cloning and differential screening constitutes an efficient approach to identify genes likely to be involved in the pathophysiology of MCNS.
Sahali
Djillali
D
INSERM U 99, Service de néphrologie pédiatrique, Hôpital Armand Trousseau - 75012, Paris.
Lang
Phillippe
P
Guellaen
Georges
G
Bensman
Albert
A
D000293:Adolescent; D000328:Adult; D002648:Child; D003001:Cloning, Molecular; D005819:Genetic Markers; D006801:Humans; D007668:Kidney / Q000473:pathology; D016328:NF-kappa B / Q000502:physiology; D009402:Nephrosis, Lipoid / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009404:Nephrotic Syndrome / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic
D005819:Genetic Markers; D016328:NF-kappa B