Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial
Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial
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DOI：
10.1136/annrheumdis-2018-214229
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发表时间：
2019-02-01
影响因子：
27.4
通讯作者：
Klatzmann, David
中科院分区：
文献类型：
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作者：
Rosenzwajg, Michelle;Lorenzon, Roberta;Klatzmann, David
目的调节性T细胞（Regulatory T cells，Tcells）具有预防自身免疫和控制炎症的作用。因此，任何自身免疫性或炎症性疾病都显示Treg不足。由于低剂量白细胞介素-2（ld-IL 2）可扩增并激活TCLs，因此具有广泛的治疗潜力。Aim我们旨在通过交叉研究ld-IL 2在治疗11种自身免疫性疾病中的1种的单一临床试验中的作用，评估这种潜力并选择疾病进行进一步的临床开发。在46例轻度至中度类风湿性关节炎、强直性脊柱炎、系统性红斑狼疮、银屑病、白塞氏病、肉芽肿伴多血管炎、高安病、克罗恩病、溃疡性结肠炎、自身免疫性肝炎和硬化性胆管炎患者中进行的I-IIa期研究。他们都接受了ld-IL 2（1百万IU/天）5天，然后每两周注射一次，持续6个月。结果ld-IL 2对各种疾病和伴随治疗耐受性良好。全面监督和无监督的免疫监测显示所有患者中的特异性Treg扩增和活化，而无效应T细胞活化。结论IL-2的剂量和治疗方案选择性地激活和扩增T淋巴细胞，并且在不同疾病和伴随治疗中是安全的。这和临床疗效的初步迹象应许可在各种自身免疫性和炎症性疾病中启动ld-IL 2的II期疗效试验。
Objective Regulatory T cells (Tregs) prevent autoimmunity and control inflammation. Consequently, any autoimmune or inflammatory disease reveals a Treg insufficiency. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential.Aim We aimed to assess this potential and select diseases for further clinical development by cross-investigating the effects of ld-IL2 in a single clinical trial treating patients with 1 of 11 autoimmune diseases.Methods We performed a prospective, open-label, phase I-IIa study in 46 patients with a mild to moderate form of either rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Behcet's disease, granulomatosis with polyangiitis, Takayasu's disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis and sclerosing cholangitis. They all received ld-IL2 (1 million IU/day) for 5 days, followed by fortnightly injections for 6 months. Patients were evaluated by deep immunomonitoring and clinical evaluation.Results ld-IL2 was well tolerated whatever the disease and the concomitant treatments. Thorough supervised and unsupervised immunomonitoring demonstrated specific Treg expansion and activation in all patients, without effector T cell activation. Indication of potential clinical efficacy was observed.Conclusion The dose of IL-2 and treatment scheme used selectively activate and expand Tregs and are safe across different diseases and concomitant treatments. This and preliminary indications of clinical efficacy should licence the launch of phase II efficacy trial of ld-IL2 in various autoimmune and inflammatory diseases.