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10.1136/annrheumdis-2017-212794 http://scihub22266oqcxt.onion/10.1136/annrheumdis-2017-212794 C6029643!6029643!29475858     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Ann+Rheum+Dis 2018 ; 77 (7): 1070-7 Nephropedia Template TP {{tp|p=29475858|t=2018. The STAT4 SLE risk allele rs7574865 T is associated with increased IL-12-induced IFN-? production in T cells from patients with SLE |pdf=|usr=}}{{29475858}} gab.com Text The STAT4 SLE risk allele rs7574865 T is associated with increased IL-12-induced IFN- production in T cells from patients with SLE JO: Ann Rheum Dis http://www.kidney.de/pget.php?&tw=1&pmid=29475858 #FOAvip Objectives: Genetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-?, IFN-? or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-?+ cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2. Cellular responses and phenotypes were correlated to STAT4 risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-?-induced activation of SLE PBMCs. Results: In resting PBMCs, the STAT4 risk allele was neither associated with total levels of STAT4 or STAT1, nor cytokine-induced pSTAT4 or pSTAT1. Following PHA/IL-2 activation, CD8+ T cells from STAT4 risk allele carriers displayed increased levels of STAT4 resulting in increased pSTAT4 in response to IL-12 and IFN-?, and an augmented IL-12-induced IFN-? production in CD8+ and CD4+ T cells. The TYK2i and the JAK2i efficiently blocked IL-12 and IFN-?-induced activation of PBMCs from STAT4 risk patients, respectively. Conclusions: T cells from patients with SLE carrying the STAT4 risk allele rs7574865[T] display an augmented response to IL-12 and IFN-?. This subset of patients may benefit from JAKi treatment. Twit Text FOAVip The STAT4 SLE risk allele rs7574865 T is associated with increased IL-12-induced IFN- production in T cells from patients with SLE ????Ann Rheum Dis http://www.kidney.de/pget.php?&tw=1&pmid=29475858 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29475858 #FOAvip English Wikipedia <ref>{{Cite pmid|29475858}}</ref> The STAT4 SLE risk allele rs7574865 T is associated with increased IL-12-induced IFN-? production in T cells from patients with SLE #MMPMID29475858 Hagberg N; Joelsson M; Leonard D; Reid S; Eloranta ML; Mo J; Nilsson MK; Syvänen AC; Bryceson YT; Rönnblom L Ann Rheum Dis 2018[Jul]; 77 (7): 1070-7 PMID29475858show ga Objectives: Genetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-?, IFN-? or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-?+ cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2. Cellular responses and phenotypes were correlated to STAT4 risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-?-induced activation of SLE PBMCs. Results: In resting PBMCs, the STAT4 risk allele was neither associated with total levels of STAT4 or STAT1, nor cytokine-induced pSTAT4 or pSTAT1. Following PHA/IL-2 activation, CD8+ T cells from STAT4 risk allele carriers displayed increased levels of STAT4 resulting in increased pSTAT4 in response to IL-12 and IFN-?, and an augmented IL-12-induced IFN-? production in CD8+ and CD4+ T cells. The TYK2i and the JAK2i efficiently blocked IL-12 and IFN-?-induced activation of PBMCs from STAT4 risk patients, respectively. Conclusions: T cells from patients with SLE carrying the STAT4 risk allele rs7574865[T] display an augmented response to IL-12 and IFN-?. This subset of patients may benefit from JAKi treatment. äThe STAT4 SLE risk allele rs7574865 T is associated with increased IL(epmc).pdf DeepDyve Pubget Overpricing