Repository logo

Browsing by Issue Date, starting with "2008-07"

Filter results by year or month
Now showing 1 - 2 of 2
  • Mutations in STAT3 and IL12RB1 impair the development of human IL-17 – producing T cells
    Publication . Beaucoudrey, L.; Puel, A.; Filipe-Santos, O.; Cobat, A.; Ghandil, P.; Chrabieh, M.; Feinberg, J.; Bernuth, H.; Samarina, A.; Jannière, L.; Fieschi, C.; Stéphan, J.; Boileau, C.; Lyonnet, S.; Jondeau, G.; Cormier-Daire, V.; Merrer, M.; Hoarau, C.; Lebranchu, Y.; Lortholary, O.; Chandesris, M.; Tron, F.; Gambineri, E.; Bianchi, L.; Rodriguez-Gallego, C.; Zitnik, S.; Vasconcelos, J.; Guedes, M.; Vitor, A.; Marodi, L.; Chapel, H.; Reid, B.; Roifman, C.; Nadal, D.; Reichenbach, J.; Caragol, I.; Garty, B.; Dogu, F.; Camcioglu, Y.; Gülle, S.; Sanal, O.; Fischer, A.; Abel, L.; Stockinger, B.; Picard, C.; Casanova, J.
    Abstract The cytokines controlling the development of human interleukin (IL) 17--producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17--producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) beta, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17--producing T cells. These data suggest that IL-12Rbeta1- and STAT-3--dependent signals play a key role in the differentiation and/or expansion of human IL-17-producing T cell populations in vivo.
    2008-07Journal article Open access Show more
  • A nonsense mutation in the LIMP-2 gene associated with progressive myoclonic epilepsy and nephrotic syndrome
    Publication . Balreira, A.; Gaspar, P.; Caiola, D.; Chaves, J.; Beirão, I.; Lima, J.; Azevedo, J.; Miranda, M.
    Abstract The main clinical features of two siblings from a consanguineous marriage were progressive myoclonic epilepsy without intellectual impairment and a nephrotic syndrome with a strong accumulation of C1q in capillary loops and mesangium of kidney. The biochemical analysis of one of the patients revealed a normal beta-glucocerebrosidase activity in leukocytes, but a severe enzymatic deficiency in cultured skin fibroblasts. This deficiency suggested a defect in the intracellular sorting pathway of this enzyme. The sequence analysis of the gene encoding LIMP-2 (SCARB2), the sorting receptor for beta-glucocerebrosidase, confirmed this hypothesis. A homozygous nonsense mutation in codon 178 of SCARB2 was found in the patient, whereas her healthy parents were heterozygous for the mutation. Besides lacking immunodetectable LIMP-2, patient fibroblasts also had decreased amounts of beta-glucocerebrosidase, which was mainly located in the endoplasmic reticulum, as assessed by its sensitivity to Endo H. This is the first report of a mutation in the SCARB2 gene associated with a human disease, which, contrary to earlier proposals, shares no features with Charcot-Marie-Tooth disease both at the clinical and neurophysiological levels.
    2008-07-15Journal article Open access Show more