The universal effects of low-dose interleukin-2 across 13 autoimmune diseases in a basket clinical trial.

Autoimmunity Biotherapy Immunotherapy Inflammation Tolerance

Journal

Journal of autoimmunity
ISSN: 1095-9157
Titre abrégé: J Autoimmun
Pays: England
ID NLM: 8812164

Informations de publication

Date de publication:
07 Feb 2024
Historique:
received: 06 11 2023
revised: 15 01 2024
accepted: 25 01 2024
medline: 9 2 2024
pubmed: 9 2 2024
entrez: 8 2 2024
Statut: aheadofprint

Résumé

A Tregs insufficiency is central to autoimmune and inflammatory diseases pathophysiology and low dose interleukin-2 (IL-2 To assess IL-2 81 patients treated with IL-2 Our study unveiled a universal and significant expansion and activation of Tregs, without concomitant Teffs activation, across all 13 autoimmune diseases. Both Proleukin® and ready-to-use ILT-101® demonstrated identical effects on Tregs. CGI scores reflecting activity, severity, and efficacy were significantly reduced in the overall patient population. Disease-specific clinical scores improved in five of the six disease cohorts with at least six patients, namely ankylosing spondylitis, systemic lupus erythematosus, Behçet's disease, Sjögren's syndrome, and systemic sclerosis. Urticaria was the only severe adverse event related to treatment. IL-2 Tregs stimulation by IL-2

Sections du résumé

BACKGROUND BACKGROUND
A Tregs insufficiency is central to autoimmune and inflammatory diseases pathophysiology and low dose interleukin-2 (IL-2
OBJECTIVE OBJECTIVE
To assess IL-2
METHODS METHODS
81 patients treated with IL-2
RESULTS RESULTS
Our study unveiled a universal and significant expansion and activation of Tregs, without concomitant Teffs activation, across all 13 autoimmune diseases. Both Proleukin® and ready-to-use ILT-101® demonstrated identical effects on Tregs. CGI scores reflecting activity, severity, and efficacy were significantly reduced in the overall patient population. Disease-specific clinical scores improved in five of the six disease cohorts with at least six patients, namely ankylosing spondylitis, systemic lupus erythematosus, Behçet's disease, Sjögren's syndrome, and systemic sclerosis. Urticaria was the only severe adverse event related to treatment.
CONCLUSION CONCLUSIONS
IL-2
CLINICAL IMPLICATION CONCLUSIONS
Tregs stimulation by IL-2

Identifiants

DOI: 10.1016/j.jaut.2024.103172 PMID: 38330545
pubmed: 38330545
pii: S0896-8411(24)00006-4
doi: 10.1016/j.jaut.2024.103172
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

103172

Informations de copyright

Copyright © 2024. Published by Elsevier Ltd.

Auteurs

Roberta Lorenzon (R)

Assistance Publique - Hopitaux de Paris, Biotherapies Department, Pitié-Salpêtrière Hospital, Paris, Île-de-France, France; Sorbonne Universite, INSERM, UMR_S 959, Immunology-Immunopathology- Immunotherapy (i3) Laboratory, Paris, Île-de-France, France.

Claire Ribet (C)

Assistance Publique - Hopitaux de Paris, Biotherapies Department, Pitié-Salpêtrière Hospital, Paris, Île-de-France, France; Sorbonne Universite, INSERM, UMR_S 959, Immunology-Immunopathology- Immunotherapy (i3) Laboratory, Paris, Île-de-France, France.

Fabien Pitoiset (F)

Assistance Publique - Hopitaux de Paris, Biotherapies Department, Pitié-Salpêtrière Hospital, Paris, Île-de-France, France; Sorbonne Universite, INSERM, UMR_S 959, Immunology-Immunopathology- Immunotherapy (i3) Laboratory, Paris, Île-de-France, France.

Selim Aractingi (S)

Assistance Publique - Hopitaux de Paris, Dermatology Department, Cochin Hospital, Paris, Île-de-France, France.

Beatrice Banneville (B)

Assistance Publique - Hopitaux de Paris, Rheumatology Department, Pitié-Salpêtrière Hospital, Paris, Île-de-France, France.

Laurent Beaugerie (L)

Assistance Publique - Hopitaux de Paris, Gastroenterology Department, Saint-Antoine Hospital, Paris, Île-de-France, France; Sorbonne Universite, GRC-UPMC 03, Paris, Île-de-France, France.

Francis Berenbaum (F)

Assistance Publique - Hopitaux de Paris, Rheumatology Department, Saint-Antoine Hospital Paris, Île-de-France, France; Sorbonne Universite, INSERM UMR_S938, Paris, Île-de-France, France.

Patrice Cacoub (P)

Assistance Publique - Hopitaux de Paris, Internal Medicine and Clinical Immunology Department, Pitié-Salpêtrière Hospital, Paris, Île-de-France, France.

Julien Champey (J)

Assistance Publique - Hopitaux de Paris, Rheumatology Department, Saint-Antoine Hospital Paris, Île-de-France, France.

Olivier Chazouilleres (O)

Assistance Publique - Hopitaux de Paris, Hepatology Department, Saint-Antoine Hospital, Paris, Île-de-France, France.

Christophe Corpechot (C)

Assistance Publique - Hopitaux de Paris, Hepatology Department, Saint-Antoine Hospital, Paris, Île-de-France, France.

Bruno Fautrel (B)

Assistance Publique - Hopitaux de Paris, Rheumatology Department, Pitié-Salpêtrière Hospital, Paris, Île-de-France, France; Sorbonne Universite, GRC08 - IPLESP, Paris, Île-de-France, France.

Arsène Mekinian (A)

Assistance Publique - Hopitaux de Paris, Internal Medicine Department, Saint-Antoine Hospital, Paris, Île-de-France, France.

Elodie Regnier (E)

Assistance Publique - Hopitaux de Paris, Dermatology Department, Cochin Hospital, Paris, Île-de-France, France.

David Saadoun (D)

Assistance Publique - Hopitaux de Paris, Internal Medicine and Clinical Immunology Department, Pitié-Salpêtrière Hospital, Paris, Île-de-France, France.

Joe-Elie Salem (JE)

INSERM, CIC-1901, Pitié-Salpêtrière Hospital, Paris, Île-de-France, France; Assistance Publique - Hopitaux de Paris, Pharmacology Department, Pitié-Salpêtrière Hospital, Paris, Île-de-France, France.

Jérémie Sellam (J)

Assistance Publique - Hopitaux de Paris, Rheumatology Department, Saint-Antoine Hospital Paris, Île-de-France, France; Sorbonne Universite, INSERM UMR_S938, Paris, Île-de-France, France.

Philippe Seksik (P)

Assistance Publique - Hopitaux de Paris, Gastroenterology Department, Saint-Antoine Hospital, Paris, Île-de-France, France; Sorbonne Universite, GRC-UPMC 03, Paris, Île-de-France, France.

Eric Vicaut (E)

Assistance Publique - Hopitaux de Paris, Clinical Research Unit, Lariboisiere Fernand-Widal Hospital, Paris, Île-de-France, France.

Michelle Rosenzwajg (M)

Assistance Publique - Hopitaux de Paris, Biotherapies Department, Pitié-Salpêtrière Hospital, Paris, Île-de-France, France; Sorbonne Universite, INSERM, UMR_S 959, Immunology-Immunopathology- Immunotherapy (i3) Laboratory, Paris, Île-de-France, France.

David Klatzmann (D)

Assistance Publique - Hopitaux de Paris, Biotherapies Department, Pitié-Salpêtrière Hospital, Paris, Île-de-France, France; Sorbonne Universite, INSERM, UMR_S 959, Immunology-Immunopathology- Immunotherapy (i3) Laboratory, Paris, Île-de-France, France. Electronic address: david.klatzmann@sorbonne-universite.fr.

Classifications MeSH