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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 | Functional dichotomy of A20 in apoptotic and necrotic cell death显示文摘 | Storz P Doppler H Ferran C | 2005 | J Bio Chem2005，387，1： | 1 |
| 3 | Device-to-device communicationunder-laying cellular communications systems显示文摘 | JANIS P YU C DOPPLER K | 2009 | International JounalCommunications Network and System Sciences2009，2，3： | 1 |
| 4 | Device-to-device communication as an underlay to LTE-advanced networks 显示文摘 | Doppler K Rinne M Wijting C Ribeiro C Hugl K | 2009 | Communications Magazine IEEE Dec2009，47，12： | 1 |
| 5 | Device to-device communication as an underlay to LTE-advanced networks显示文摘 | Doppler K Rinne M Wijting C | 2009 | IEEE Communications Magazine2009，47，12： | 1 |
| 6 | Device to-device com-munication as an underlay to LTE-advanced networks显示文摘 | DOPPLER K RINNE M R1BEIRO C | 2009 | IEEE Com-munications Magazine2009，47，12： | 1 |
| 7 | Increased bas- al transepidermal water loss leads to elevati on of some but not all stratum corneum serine proteases 显示文摘 | Vogeli R Rawlings AV Doppler S | 2008 | Int J Cosmet Sci2008，30，6： | 1 |
| 8 | Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species显示文摘 | Storz P Doppler H Toker A | 2005 | Mol Cell Biol2005，25，19： | 1 |
| 9 | Added value of measuring pre- and postejection velocities in ischemic myocar- dium显示文摘 | Edvardsen T Urheim S Skulstad H Quantification of left ven- tricular systolic function by tissue Doppler echocardiography | 2002 | Circulation2002，105，17： | 1 |
| 10 | Induction of v-mos and activated Ha-ras oncogene expression in quiescent NIH 3T3 cells causes intracellular alkalinisation and cell-cycle progression显示文摘 | DOPPLER W JAGGI R CRONER B | | 0，，01： | 1 |
| 11 | Device-to-Device com- munication underlaying cellular communication systems 显示文摘 | JANIS P YU Chiahao DOPPLER K | 2009 | Inter- national Journal on Communications Networking and System S- cience2009，2，3： | 1 |
| 12 | Resource sha- ring optimization for device-to-device communication underlaying cellular networks显示文摘 | Yu C H Doppler K Ribeiro C B | 2011 | IEEE Transactions on Wireless Communications2011，10，8： | 1 |
| 13 | A potentially useful alternative to mean frequency - base color Doppler US 显示文摘 | Rubin JM Adler RS Power Doppler US | 1994 | Radiology1994，190，8： | 1 |
| 14 | Critical limb ischaemia is characterised by an increased production of whole blood reactive oxygen species and expression of TREM-1 on neutrophils 显示文摘 | Dopheide JF Doppler C Scheer M | 2013 | Atheroselerosis2013，29，2： | 1 |
| 15 | The impact of water price strategies on the allocation of irrigation water: the case of the Jordan Valley 显示文摘 | Doppler W Salman A Z Al-Karablieh E K | 2002 | Agricultural Water Management2002，55，： | 1 |
| 16 | Device-to-device communication underlaying cellular communications systems 显示文摘 | JNIS P YU C H DOPPLER K | 2009 | International joumal of communications network and system sciences2009，2，3： | 1 |
| 17 | Device-to-Device Communication as an Underlay to LTE-Advanced Networks 显示文摘 | DOPPLER K RINNE M WILTING C | 2009 | IEEE Communications Magzine2009，47，12： | 1 |
| 18 | Protein kinase D regulates cofilin activity through p21-activated kinase 4 显示文摘 | Spratley S J Bastea LI Doppler H | 2011 | J Biol Chem2011，286，34： | 1 |
| 19 | Device-to-device communi- cation as an underlay to LTE-advanced networks 显示文摘 | Doppler K Rinne M Wiiting C | 2009 | IEEE Communications Magazine2009，47，12： | 1 |
| 20 | Tetralogy of Fallot and hypoplastic left heart syndrome -complex clinical phenotypes meet complex genetic networks显示文摘 | Lahm H SchSn P Doppler S | 2015 | Current Genomics2015，16，3： | 1 |
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