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Factors affecting long-term efficacy of T regulatory cell-based therapy in type 1 diabetes.

ABSTRACT: BACKGROUND:Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment. METHODS:The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 × 106/kg b.w. of autologous expanded CD3+CD4+CD25highCD127- Tregs. RESULTS:The disease progressed and all patients were insulin-dependent 2 years after inclusion. The ?-cell function measured by c-peptide levels and the use of insulin were the best preserved in patients treated with two doses of Tregs (3/6 in remission), less so after one dose (1/6 in remission) and the worst in untreated controls (no remissions). Increased levels of Tregs could be seen in peripheral blood after their adoptive transfer together with the shift from naïve CD62L+CD45RA+ to memory CD62L+CD45RA- Tregs. Increasing serum levels of proinflammatory cytokines were found: IL6 increased in all subjects, while IL1 and TNF? increased only in untreated group. Therapeutic Tregs were dependent on IL2, and their survival could be improved by other lymphocytes. CONCLUSIONS:The disease progression was associated with changing proportions of naïve and memory Tregs and slowly increasing proinflammatory activity, which was only partially controlled by the administered Tregs. The therapeutic cells were highly dependent on IL2. We conclude that the therapy should be administered at the earliest to protect the highest possible mass of islets and also to utilize the preserved content of Tregs in the earlier phases of T1DM. Trial registration http://www.controlled-trials.com/ISRCTN06128462 ; registered retrospectively.

SUBMITTER: Marek-Trzonkowska N

PROVIDER: S-EPMC5131539 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Factors affecting long-term efficacy of T regulatory cell-based therapy in type 1 diabetes.

Marek-Trzonkowska Natalia N Myśliwiec Małgorzata M Iwaszkiewicz-Grześ Dorota D Gliwiński Mateusz M Derkowska Ilona I Żalińska Magdalena M Zieliński Maciej M Grabowska Marcelina M Zielińska Hanna H Piekarska Karolina K Jaźwińska-Curyłło Anna A Owczuk Radosław R Szadkowska Agnieszka A Wyka Krystyna K Witkowski Piotr P Młynarski Wojciech W Jarosz-Chobot Przemysława P Bossowski Artur A Siebert Janusz J Trzonkowski Piotr P

Journal of translational medicine 20161201 1

<h4>Background</h4>Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment.<h4>Methods</h4>The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 × 10<sup>6</sup>/kg b.w. of autologous expanded CD3<sup>+</sup>CD4<sup>+ ...[more]

PMID: 27903296

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Project description:PurposeThe purpose of this study was to investigate the long-term outcomes 1 year after undertaking an audiologist-guided Internet-based cognitive behavioral therapy (iCBT) intervention for tinnitus. Secondary aims were to identify any predictors of outcome and whether there were any unwanted events related to undertaking iCBT for tinnitus.MethodParticipants who had previously undertaken a randomized iCBT efficacy trial for tinnitus were invited to participate. Of the 146 who were initially randomized for the efficacy trial, 104 participants completed the 1-year postintervention assessment measures. The primary outcome was a change in tinnitus distress as assessed by the Tinnitus Functional Index. Secondary assessment measures were included for insomnia, anxiety, depression, hearing handicap, hyperacusis, cognitive failures, and satisfaction with life. An intention-to-treat analysis using repeated-measures analysis of variance and hierarchical multiple regression was used for statistical analysis. Unwanted effects were categorized according to the unwanted events checklist.ResultsUndertaking iCBT for tinnitus led to significant improvements 1 year postintervention for tinnitus and related difficulties, for example, insomnia, anxiety, depression, hearing handicap, hyperacusis, and life satisfaction. The best predictors of improving tinnitus severity at 1-year postintervention were greater baseline tinnitus severity scores, reading more of the modules, and higher satisfaction with the intervention. Unwanted events were reported by 11% of the participants and were more likely to be reported by women than men. These events were related to worsening of symptoms, the emergence of new symptoms, negative well-being, and prolongation of treatment.ConclusionsThe clinical benefits of audiologist-guided iCBT for tinnitus and tinnitus-related difficulties were sustained 1 year postintervention. Predictors of outcome indicated that the intervention is applicable to a wide range of participants regardless of their demographic backgrounds. Attempts should be made to minimize unwanted events in subsequent trials.

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Factors affecting long-term efficacy of T regulatory cell-based therapy in type 1 diabetes.

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Factors affecting long-term efficacy of T regulatory cell-based therapy in type 1 diabetes.

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