{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:13:43Z","timestamp":1793726023058,"version":"4.6.1"},"reference-count":28,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"unspecified","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2024,3,12]]},"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Systemic sclerosis (SSc) is a chronic autoimmune disease, with impaired immune response, increased fibrosis and endothelial dysfunction. Regulatory T cells (Tregs), which are essential to control inflammation, tissue repair and autoimmunity, have a decreased frequency and impaired function in SSc patients. Low-dose interleukin-2 (IL-2<jats:sub>LD<\/jats:sub>) can expand and activate Tregs and has, therefore, a therapeutic potential in SSc.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We aimed to assess the safety and biological efficacy of IL-2<jats:sub>LD<\/jats:sub> in patients with SSc.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>As part of the TRANSREG open-label phase IIa basket trial in multiple autoimmune diseases, we studied nine patients with SSc without severe organ involvement. Patients received 1 million international units (MIU)\/day of IL-2 for 5\u2009days, followed by fortnightly injections for 6\u2009months. Laboratory and clinical evaluations were performed between baseline and month 6.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At day 8, the primary endpoint (Treg frequency) was reached with a 1.8\u00b10.5-fold increase of Treg levels among CD4<jats:sup>+<\/jats:sup> T lymphocytes (p=0.0015). There were no significant changes in effector T cells nor in B cells. IL-2<jats:sub>LD<\/jats:sub> was well tolerated, and no serious adverse events related to treatment occurred. There was a globally stable measurement in the modified Rodnan skin score and Valentini score at month 6. Disease activity and severity measures, the quality of life evaluated by EuroQL-5D-5L and pulmonary function test parameters remained stable during the study period.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>IL-2<jats:sub>LD<\/jats:sub> at a dosage of 1 MIU\/day safely and selectively activates and expands Tregs. Clinical signs remain stable during the study period. This opens the door to properly powered phase II efficacy trials investigating IL-2<jats:sub>LD<\/jats:sub> therapeutic efficacy in SSc.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2023-003500","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T04:00:48Z","timestamp":1712289648000},"page":"e003500","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Induction of regulatory T cells and efficacy of low-dose interleukin-2 in systemic sclerosis: interventional open-label phase 1\u2013phase 2a study"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct01988506","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01988506","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-225X","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Barde","sequence":"first","affiliation":[{"name":"Service de m\u00e9decine interne, AP-HP, H\u00f4pital Saint Antoine, Sorbonne Universite, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Lorenzon","sequence":"additional","affiliation":[{"name":"Clinical Investigation Center for Biotherapies and Inflammation-Immunopathology-Biotherapy Department (i2B), AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Sorbonne Universite, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Vicaut","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de recherche clinique, AP-HP, H\u00f4pital Lariboisi\u00e8re, Paris Cit\u00e9 University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Rivi\u00e8re","sequence":"additional","affiliation":[{"name":"Service de m\u00e9decine interne, AP-HP, H\u00f4pital Saint Antoine, Sorbonne Universite, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Cacoub","sequence":"additional","affiliation":[{"name":"Service de m\u00e9decine interne et immunologie clinique, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Sorbonne Universite, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Cacciatore","sequence":"additional","affiliation":[{"name":"Service de m\u00e9decine interne, AP-HP, H\u00f4pital Saint Antoine, Sorbonne Universite, Paris, 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