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10.1002/hep.29148 http://scihub22266oqcxt.onion/10.1002/hep.29148 C5850982!5850982 !28295463     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28295463 &cmd=llinks): Failed to open stream: HTTP request failed! 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Immune phenotype and function of natural killer and T cells in chronic hepatitis C patients who received a single dose of anti-MicroRNA-122, RG-101 |pdf=|usr=}}{{28295463 }} gab.com Text Immune phenotype and function of natural killer and T cells in chronic hepatitis C patients who received a single dose of anti-MicroRNA-122, RG-101 JO: Hepatology http://www.kidney.de/pget.php?&tw=1&pmid=28295463 #FOAvip MicroRNA-122 is an important host factor for the hepatitis C virus (HCV). Treatment with RG-101, an N-acetylgalactosamine-conjugated anti-microRNA-122 oligonucleotide, resulted in a significant viral load reduction in patients with chronic HCV infection. Here, we analyzed the effects of RG-101 therapy on antiviral immunity. Thirty-two chronic HCV patients infected with HCV genotypes 1, 3, and 4 received a single subcutaneous administration of RG-101 at 2 mg/kg (n = 14) or 4 mg/kg (n = 14) or received a placebo (n = 2/dosing group). Plasma and peripheral blood mononuclear cells were collected at multiple time points, and comprehensive immunological analyses were performed. Following RG-101 administration, HCV RNA declined in all patients (mean decline at week 2, 3.27 log10 IU/mL). At week 8 HCV RNA was undetectable in 15/28 patients. Plasma interferon-?-induced protein 10 (IP-10) levels declined significantly upon dosing with RG-101. Furthermore, the frequency of natural killer (NK) cells increased, the proportion of NK cells expressing activating receptors normalized, and NK cell interferon-? production decreased after RG-101 dosing. Functional HCV-specific interferon-? T-cell responses did not significantly change in patients who had undetectable HCV RNA levels by week 8 post-RG-101 injection. No increase in the magnitude of HCV-specific T-cell responses was observed at later time points, including 3 patients who were HCV RNA-negative 76 weeks postdosing. CONCLUSION: Dosing with RG-101 is associated with a restoration of NK-cell proportions and a decrease of NK cells expressing activation receptors; however, the magnitude and functionality of ex vivo HCV-specific T-cell responses did not increase following RG-101 injection, suggesting that NK cells, but not HCV adaptive immunity, may contribute to HCV viral control following RG-101 therapy. (Hepatology 2017;66:57-68). Twit Text FOAVip Immune phenotype and function of natural killer and T cells in chronic hepatitis C patients who received a single dose of anti-MicroRNA-122, RG-101 ????Hepatology http://www.kidney.de/pget.php?&tw=1&pmid=28295463 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28295463 #FOAvip English Wikipedia <ref>{{Cite pmid|28295463 }}</ref> Immune phenotype and function of natural killer and T cells in chronic hepatitis C patients who received a single dose of anti-MicroRNA-122, RG-101 #MMPMID28295463 Stelma F ; van der Ree MH ; Sinnige MJ ; Brown A ; Swadling L ; de Vree JML ; Willemse SB ; van der Valk M ; Grint P ; Neben S ; Klenerman P ; Barnes E ; Kootstra NA ; Reesink HW Hepatology 2017[Jul]; 66 (1 ): 57-68 PMID28295463 show ga MicroRNA-122 is an important host factor for the hepatitis C virus (HCV). Treatment with RG-101, an N-acetylgalactosamine-conjugated anti-microRNA-122 oligonucleotide, resulted in a significant viral load reduction in patients with chronic HCV infection. Here, we analyzed the effects of RG-101 therapy on antiviral immunity. Thirty-two chronic HCV patients infected with HCV genotypes 1, 3, and 4 received a single subcutaneous administration of RG-101 at 2 mg/kg (n = 14) or 4 mg/kg (n = 14) or received a placebo (n = 2/dosing group). Plasma and peripheral blood mononuclear cells were collected at multiple time points, and comprehensive immunological analyses were performed. Following RG-101 administration, HCV RNA declined in all patients (mean decline at week 2, 3.27 log10 IU/mL). At week 8 HCV RNA was undetectable in 15/28 patients. Plasma interferon-?-induced protein 10 (IP-10) levels declined significantly upon dosing with RG-101. Furthermore, the frequency of natural killer (NK) cells increased, the proportion of NK cells expressing activating receptors normalized, and NK cell interferon-? production decreased after RG-101 dosing. Functional HCV-specific interferon-? T-cell responses did not significantly change in patients who had undetectable HCV RNA levels by week 8 post-RG-101 injection. No increase in the magnitude of HCV-specific T-cell responses was observed at later time points, including 3 patients who were HCV RNA-negative 76 weeks postdosing. CONCLUSION: Dosing with RG-101 is associated with a restoration of NK-cell proportions and a decrease of NK cells expressing activation receptors; however, the magnitude and functionality of ex vivo HCV-specific T-cell responses did not increase following RG-101 injection, suggesting that NK cells, but not HCV adaptive immunity, may contribute to HCV viral control following RG-101 therapy. (Hepatology 2017;66:57-68). |Dose-Response Relationship, Drug [MESH] |Double-Blind Method [MESH] |Drug Administration Schedule [MESH] |Enzyme-Linked Immunospot Assay/methods [MESH] |Female [MESH] |Flow Cytometry [MESH] |Follow-Up Studies [MESH] |Hepatitis C, Chronic/diagnosis/*drug therapy [MESH] |Humans [MESH] |Injections, Subcutaneous [MESH] |Killer Cells, Natural/*drug effects/immunology [MESH] |Male [MESH] |MicroRNAs/administration & dosage/*antagonists & inhibitors [MESH] |Middle Aged [MESH] |Molecular Targeted Therapy/methods [MESH] |Netherlands [MESH] |Phenotype [MESH] |T-Lymphocytes/*drug effects/immunology [MESH]Immune phenotype and function of natural killer and T cells in chronic(epmc).pdf DeepDyve Pubget Overpricing