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| 1 | 低剂量白细胞介素-2在11种自身免疫疾病中的免疫学和临床疗效:单中心开放临床试验显示文摘背景调节性T(Tregs)细胞可以预防自身免疫并控制炎症,在各种自身免疫性或自身炎症性疾病中的研究都表明Treg细胞不足。由于低剂量白细胞介素-2(low-dose interleukin-2,ld-IL2)能够扩增并激活Tregs细胞,因此ld-IL2具有广泛的治疗潜力。目的我们通过一项临床试验观察ld-IL2治疗11种自身免疫性疾病中1种的效果,旨在评估ld-IL2的治疗潜力并选择疾病,以用于进一步的临床开发。方法本研究为前瞻开放性Ⅰ~Ⅱa期临床观察,入选了46例轻中度患者,诊断分别为类风湿关节炎、强直性脊柱炎、系统性红斑狼疮、牛皮癣、白塞病、肉芽肿性多血管炎、大动脉炎、克罗恩病、溃疡性结肠炎、自身免疫性肝炎或硬化性胆管炎。所有患者都接受了ld-IL2(100万IU/天)5天,然后每两周注射一次,维持6个月。所有患者均接受了深入的免疫监测和临床评估。结果在任何疾病类型以及任何合并药物治疗的患者中,ld-IL2都显示出了良好的耐受性。通过经典的免疫表型分析和广泛的免疫表型分析发现所有患者的Tregs细胞均被特异性地扩增激活,而效应T细胞没有被活化,提示ld-IL2具有临床疗效的前景。结论本研究中所采用的IL-2剂量和治疗方案可以选择性地激活和扩增Tregs细胞,并且对于不同的疾病种类以及不同的合并用药都是安全的。这一临床疗效以及初步结果可以为ld-IL2在各种自身免疫和自身炎症性疾病中开展Ⅱ期临床试验观察疗效提供了依据。试验注册号NCT01988506. | Michelle Rosenzwajg Roberta Lorenzon Patrice Cacoub Hang Phuong Pham Fabien Pitoiset Karim El Soufi Claire RIbet Claude Bernard Selim Aractingi Beatrice Banneville Laurent Beaugerie Francis Berenbaum Julien Champey Olivier Chazouilleres Christophe Corpechot Bruno Fautrel Arsfene Mekinian Elodie Regnier David Saadoun Joe-Elie Salem Jeremie Sellam Philippe Seksik Anne Daguenel-Nguyen Valene Doppler Jeremie Mariau Eric Vicaut David Klatzmann 杨新蕾(译) 张卓莉(校) | 2019 | 英国医学杂志中文版2019，22，2： | 2 |
| 2 | Increased levels of circu- lating microparticles in primary Sjcigren's syndrome, systemic lupus erythematosus and rheumatoid arthritis and relation with disease activity显示文摘 | Sellam J Proulle V Jungel A | 2009 | Arthritis Res Ther2009，11，： | 1 |
| 3 | The zinc cluster transcription factor Ahr1p directs Mcm1p regulation of Candida albicans adhesion显示文摘 | Askew C Sellam A Epp E | 2011 | Mol Microbiol2011，79，4： | 1 |
| 4 | The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis 显示文摘 | Sellam J Berenbaum F | 2010 | Nat Rev Rheumatol2010，6，： | 1 |
| 5 | Characterization of Mutations in the Iron-Sulphur Subunit of Succinate Dehydrogenase Correlating with Boscalid Resistance in Alternaria alternata from California Pistachio显示文摘 | H F Avenot A Sellam G Karaoglanidis | 2008 | Phytopathology2008，98，6： | 1 |
| 6 | Contextual factors associated with pain response of preterm infants to heel-stick procedures显示文摘 | Sellam G Engberg S Denhaerynck KD | 2013 | Pain2013，17，： | 1 |
| 7 | The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis 显示文摘 | Sellam J Berenbaum F | 2010 | Nat Rev Rheumatol2010，6，11： | 1 |
| 8 | Characterization of mutations in the iron-sulphur subunit of succinate dehydrogenase correlating with boscalid resistance in A lternaria alternata from California Pistachio 显示文摘 | AVENOT H F SELLAM A KARAOGLANIDIS G | 2008 | Phytopathology2008，98，6： | 1 |
| 9 | A rare form of rifampicininduced skin toxicity:bulloas pemphigoid显示文摘 | Ibn Sellam A Soualhi M Zahraani R | 2011 | Rev Mat Respir2011，28，3： | 1 |
| 10 | No evidence for an association between the -871 T/C promoter polymorphism in the B-cell-activating factor gene and primary Sjogren's syndrome显示文摘 | GOTTENBERG J E SELLAM J ITTAH M | 2006 | Arthritis Res Ther2006，8，： | 1 |
| 11 | The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis显示文摘 | Sellam J Berenbaum F | 2010 | Nat Rev Rheumatol2010，6，11： | 1 |
| 12 | Oral sucrose and ' facilitatedtucking' for repeated pain relief in preterms : A randomized controlledtrial 显示文摘 | Cignacco EL Sellam G Stoffel L | 2012 | Pediatrics2012，129，2： | 1 |
| 13 | Refractory muhicentric reticulohistiocytosis treated by infliximab: two cases 显示文摘 | Sellam J Deslandre C J Dubreuil F | 2005 | Clin Exp Rheumatol2005，23，1： | 1 |
| 14 | Refractory muhicentric retic - ulohistiocytosis treated by infliximab: two cases 显示文摘 | Sellam J Deslander C J Dubreuil F | 2005 | Chn Exp Rheumatol2005，23，1： | 1 |
| 15 | The role of synovitis in pathophysiol- ogy and clinical symptoms of osteoarthritis 显示文摘 | Sellam Berenbaum F | 2010 | Nat Rev Rheumatol2010，6，11： | 1 |
| 16 | Increased risks of lymphoma and death among patients with non-hepatitis C virus- related mixed cryoglobulinemia 显示文摘 | Saadoun D Sellam J Ghillani-Dalbin P | 2006 | Arch Intern Med2006，166，19： | 1 |
| 17 | Activity of Ni substituted Ca-La-hexaaluminate catalyst in dry reforming of methane显示文摘 | Ikkour K Sellam D Kiennemann A | 2009 | Catalysis Letters2009，132，12： | 1 |
| 18 | Experience of intra- venous immunoglobulin therapy in neuropathy associated with primary Sjogren's syndrome:A national multicentric retrospective study显示文摘 | Rist S Sellam J Hachulla E | 2011 | Arthritis Care Res2011，63，9： | 1 |
| 19 | Decreased B cell acti- vating factor receptor expression on peripheral lymphocytes associated whth increased disease avtivity in primary Sjogren's syndrome and sys- temic lupus erythematosus 显示文摘 | Sellam J Miceli-Richard C Gottenberg JE | 2007 | Ann Rheum Dis2007，66，6： | 1 |
| 20 | The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis显示文摘 | SELLAM J BERE BAUM F | 2010 | Nature Reviews Rheumatology2010，6，11： | 1 |
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