{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:02:30Z","timestamp":1791576150831,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010675","name":"H2020 Innovation In SMEs","doi-asserted-by":"publisher","award":["830559 \u2010 TREG"],"award-info":[{"award-number":["830559 \u2010 TREG"]}],"id":[{"id":"10.13039\/100010675","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005632","name":"Narodowe Centrum Bada\u0144 i Rozwoju","doi-asserted-by":"publisher","award":["STRATEGMED1\/233368\/1\/NCBR\/2014"],"award-info":[{"award-number":["STRATEGMED1\/233368\/1\/NCBR\/2014"]}],"id":[{"id":"10.13039\/501100005632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Monotherapy with autologous expanded CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD25\n                      <jats:sup>high<\/jats:sup>\n                      CD127\n                      <jats:sup>\u2212<\/jats:sup>\n                      T regulatory cells (Tregs) or rituximab has been documented to slow disease progression in patients with recent\u2010onset type 1 diabetes mellitus (T1DM). Whether a combined therapy including both drugs would further benefit this patient population is unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We conducted a three\u2010arms clinical trial to explore the efficacy and safety of the combined treatment with Tregs and rituximab in paediatric patients with T1DM. The patients were allocated to three groups: Tregs only (n\u00a0=\u00a013), Tregs\u2009+\u2009rituximab (n\u00a0=\u00a012) and control (n\u00a0=\u00a011). The key primary efficacy analyses were C\u2010peptide levels (mixed meal tolerance test) and the proportion of patients in remission at 12 and 24\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At month 24, as compared with the control, both treatment groups remained superior in the area under the curve of C\u2010peptide mixed meal tolerance test, whereas in the analysis of all visits only the combined therapy improved area under the curve at 12 and 24\u2009months. The proportion of patients in remission was significantly higher in the combined group than in the control group at 3, 6, 9 and 21\u2009months but not at 18 and 24\u2009months. There was no significant difference between the Tregs only group and control group. Adverse events occurred in 80% patients, mostly in the combined group and Tregs only group. No adverse events led to the withdrawal of the intervention or death. All comparisons were performed with alpha level of 5%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Over 2\u2009years, combined therapy with Tregs and rituximab was consistently superior to monotherapy in delaying T1DM progression in terms of C\u2010peptide levels and the maintenance of remission.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14723","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T23:43:23Z","timestamp":1650411803000},"page":"1534-1543","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Combined therapy with\n                    <scp>CD4<\/scp>\n                    <sup>+<\/sup>\n                    <scp>CD25highCD127<\/scp>\n                    <sup>\u2212<\/sup>\n                    T regulatory cells and\n                    <scp>anti\u2010CD20<\/scp>\n                    antibody in recent\u2010onset type 1 diabetes is superior to monotherapy: Randomized phase I\/\n                    <scp>II<\/scp>\n                    trial"],"prefix":"10.1111","volume":"24","author":[{"given":"Maciej","family":"Zieli\u0144ski","sequence":"first","affiliation":[{"name":"Department of Medical Immunology Medical University of Gda\u0144sk  Gda\u0144sk Poland"},{"name":"Poltreg S.A.  Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"\u017bali\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Diabetology and Endocrinology Medical University of Gda\u0144sk  Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Iwaszkiewicz\u2010Grze\u015b","sequence":"additional","affiliation":[{"name":"Department of Medical Immunology Medical University of Gda\u0144sk  Gda\u0144sk Poland"},{"name":"Poltreg S.A.  Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Gliwi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Medical Immunology Medical University of Gda\u0144sk  Gda\u0144sk Poland"},{"name":"Poltreg S.A.  Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matylda","family":"Hennig","sequence":"additional","affiliation":[{"name":"Department of Pediatric Diabetology and Endocrinology Medical University of Gda\u0144sk  Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ja\u017awi\u0144ska\u2010Cury\u0142\u0142o","sequence":"additional","affiliation":[{"name":"Regional Center of Blood Donation and Treatment  Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halla","family":"Kami\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Children's Diabetology Medical University of Silesia  Katowice Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Sakowska","sequence":"additional","affiliation":[{"name":"Department of Medical Immunology Medical University of Gda\u0144sk  Gda\u0144sk Poland"},{"name":"Poltreg S.A.  Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wo\u0142oszyn\u2010Durkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Diabetology and Endocrinology Medical University of Gda\u0144sk  Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rados\u0142aw","family":"Owczuk","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Critical Care Medical University of Gda\u0144sk  Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"M\u0142ynarski","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Oncology and Haematology Medical University of Lodz  Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemys\u0142awa","family":"Jarosz\u2010Chobot","sequence":"additional","affiliation":[{"name":"Department of Children's Diabetology Medical University of Silesia  Katowice Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Bossowski","sequence":"additional","affiliation":[{"name":"Department of Peadiatrics, Endocrinology, Diabetology with Cardiology Division Medical University of Bialystok  Bia\u0142ystok Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Szadkowska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Diabetology, Endocrinology and Nephrology Medical University of Lodz  Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"Siebert","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Laboratory of Immunoregulation and Cellular Therapies Medical University of Gda\u0144sk  Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"My\u015bliwiec","sequence":"additional","affiliation":[{"name":"Poltreg S.A.  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