Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial

被引：335

作者：

Rosenzwajg, Michelle ^{[1
,2
]}

Lorenzon, Roberta ^{[1
,2
]}

Cacoub, Patrice ^{[1
,2
,3
]}

Hang Phuong Pham ^{[4
]}

Pitoiset, Fabien ^{[1
,2
]}

El Soufi, Karim ^{[1
,2
]}

Ribet, Claire ^{[1
]}

Bernard, Claude ^{[1
,2
]}

Aractingi, Selim ^{[5
]}

Banneville, Beatrice ^{[6
]}

Beaugerie, Laurent ^{[7
]}

Berenbaum, Francis ^{[8
]}

Champey, Julien ^{[8
]}

Chazouilleres, Olivier ^{[9
]}

Corpechot, Christophe ^{[9
]}

Fautrel, Bruno ^{[6
]}

Mekinian, Arsene ^{[10
]}

Regnier, Elodie ^{[5
]}

Saadoun, David ^{[1
,2
,3
]}

Salem, Joe-Elie ^{[11
,12
]}

Sellam, Jeremie ^{[8
]}

Seksik, Philippe ^{[7
]}

Daguenel-Nguyen, Anne ^{[13
]}

Doppler, Valerie ^{[4
]}

Mariau, Jeremie ^{[4
,8
]}

Vicaut, Eric ^{[14
,15
]}

Klatzmann, David ^{[1
,2
]}

机构：

[1] Hop La Pitie Salpetriere, AP HP, Inflammat Immunopathol Biotherapy Dept i2B, Paris, France

[2] Sorbonne Univ, Immunol Immunopathol Immunotherapy I3, INSERM, Paris, France

[3] Hop La Pitie Salpetriere, AP HP, Dept Internal Med & Clin Immunol, Paris, France

[4] ILTOO Pharma, Paris, France

[5] Cochin Hosp, AP HP, Dept Dermatol, Paris, France

[6] Hop La Pitie Salpetriere, AP HP, Dept Rheumatol, Paris, France

[7] St Antoine Hosp, AP HP, Dept Gastroenterol, Paris, France

[8] St Antoine Hosp, AP HP, Dept Rheumatol, Paris, France

[9] St Antoine Hosp, AP HP, Dept Hepatol, Paris, France

[10] St Antoine Hosp, AP HP, Dept Internal Med, Paris, France

[11] Hop La Pitie Salpetriere, AP HP, Dept Pharmacol, Paris, France

[12] Hop La Pitie Salpetriere, AP HP, CIC 1421, Paris, France

[13] St Antoine Hosp, AP HP, Dept Pharm, Paris, France

[14] Unite Rech Clin, Paris, France

[15] Univ Paris, St Louis Lariboisiere Hosp, AP HP, Paris, France

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2019年 / 78卷 / 02期

基金：

欧洲研究理事会;

关键词：

REGULATORY T-CELLS; IL-2; TOLERANCE; RESPONSES; THERAPY;

D O I：

10.1136/annrheumdis-2018-214229

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：209 / 217

页数：9

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