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The challenge of modulating β-cell autoimmunity in type 1 diabetes

Published on Jan 1, 2019in The Lancet Diabetes & Endocrinology 24.54
· DOI :10.1016/S2213-8587(18)30112-8
Mark A. Atkinson82
Estimated H-index: 82
(UF: University of Florida),
Bart O. Roep58
Estimated H-index: 58
(City of Hope National Medical Center)
+ 2 AuthorsMark Peakman52
Estimated H-index: 52
(HealthPartners)
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Abstract
Summary With the conceptual advance about four decades ago that type 1 diabetes represents an autoimmune disease, hope arose that immune-based therapies would soon emerge to prevent and reverse the disorder. However, despite dozens of clinical trials seeking to achieve these goals, the promise remains unfulfilled, at least in a pragmatic form. With the benefit of hindsight, several important reasons are likely to account for this disappointing outcome, including failure to appreciate disease heterogeneity, inappropriate use of rodent models of disease, inadequacies in addressing the immunological and metabolic contributions to the disease, suboptimal trial designs, and lack of a clear understanding of the pathogenesis of type 1 diabetes. In this Series paper, we convey how recent knowledge gains in these areas, combined with efforts related to disease staging and emerging mechanistic data from clinical trials, provide cautious optimism that immune-based approaches to prevent the loss of β cells in type 1 diabetes will emerge into clinical practice.
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  • Citations (1)
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References93
Newest
Published on Jan 1, 2019in The Lancet Diabetes & Endocrinology 24.54
Bart O. Roep58
Estimated H-index: 58
(City of Hope National Medical Center),
Daniel C S Wheeler1
Estimated H-index: 1
('KCL': King's College London),
Mark Peakman52
Estimated H-index: 52
(HealthPartners)
Summary Precision medicine has emerged as a mantra for therapeutic approaches to complex diseases. The defining concept relies on a detailed insight into disease pathogenesis and therapeutic mechanism. Although the type 1 diabetes field has gained new insights into disease endotypes and indications of efficacy for several therapies, none of these is yet licensed, partly because of immune suppressive side-effects beyond control of islet autoimmunity. New strategies designed to regulate the immune...
5 Citations Source Cite
Published on Dec 1, 2018in Scientific Reports 4.01
Jason T. C. Lee1
Estimated H-index: 1
(Life Sciences Institute),
Iryna Shanina1
Estimated H-index: 1
(Life Sciences Institute)
+ 2 AuthorsJames D. Johnson2
Estimated H-index: 2
(Life Sciences Institute)
Pancreatic beta-cells are selectively destroyed by the host immune system in type 1 diabetes. Thus, drugs that preserve beta-cell mass and/or function have the potential to prevent or slow the progression of this disease. We recently reported that the use-dependent sodium channel blocker, carbamazepine, protects beta-cells from inflammatory cytokines in vitro. Here, we tested the effects of carbamazepine treatment in female non-obese diabetic (NOD) mice by supplementing LabDiet 5053 with 0.5% w/...
2 Citations Source Cite
Published on Aug 18, 2018in Journal of Dermatological Treatment 2.11
Nawaf Al-Mutairi10
Estimated H-index: 10
(Kuniv: Kuwait University),
Hesham Alaadin Abouzaid1
Estimated H-index: 1
(Farwaniya Hospital)
AbstractIntroduction: Biologics are highly effective, important treatment options for moderate-to-severe psoriasis. Biologics are well tolerated and have few side effects. However, the use of biologics in patients with concomitant chronic viral hepatitis is debatable. Recent reports have suggested a very low associated risk of reactivation of chronic hepatitis B (HBV) and C (HCB).Objective: To evaluate the safety and effectiveness of biologics for moderate to severe psoriasis patients with conco...
2 Citations Source Cite
Published on Aug 1, 2018in Journal of Clinical Investigation 12.28
Lorraine Yeo3
Estimated H-index: 3
,
Alyssa Woodwyk1
Estimated H-index: 1
(WMU: Western Michigan University)
+ 13 AuthorsGarry Dolton16
Estimated H-index: 16
(Cardiff University)
In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β cell–reactive CD8+ T cells that are detectable in the circulation, and their relationship to β cell function, are not known. Here, we tracked multiple, circulating β cell–reactive CD8+ T cell subsets and measured β cell function longitudinally for 2 years, starting...
5 Citations Source Cite
Published on Feb 1, 2018in BioDrugs 4.90
Ross A. McKinnon28
Estimated H-index: 28
(Flinders University),
Matthew C. Cook34
Estimated H-index: 34
(ANU: Australian National University)
+ 4 AuthorsJohn Prins59
Estimated H-index: 59
(UQ: University of Queensland)
Background The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern.
10 Citations Source Cite
Published on Jan 1, 2018in Diabetes, Obesity and Metabolism 6.13
Marie-Christine Dubé11
Estimated H-index: 11
(Laval University),
Martin D'Amours5
Estimated H-index: 5
(Laval University),
S. John Weisnagel23
Estimated H-index: 23
(Laval University)
Aims To investigate the effects of 24 weeks of treatment with liraglutide added to basal/bolus insulin on anthropometric and metabolic parameters in overweight participants with type 1 diabetes. Methods In a double-blind cross-over fashion, 15 participants were randomly assigned (1:1) to receive placebo (saline solution) or liraglutide for 24 weeks including a one-month titration period from 0.6 mg to 1.2 mg to 1.8 mg, in addition to their insulin. The treatment was followed by a 1 month wash-ou...
5 Citations Source Cite
Published on Jan 1, 2018in Trends in Biotechnology 13.75
Marianne Saldanha1
Estimated H-index: 1
,
Prajakta Dandekar12
Estimated H-index: 12
,
Ratnesh Jain12
Estimated H-index: 12
Antibody–drug conjugates (ADCs) and bispecific antibodies are becoming increasingly popular. However, their complex structures mandate stringent regulatory guidelines to ensure their safety and efficacy. We have briefly reviewed the existing regulatory guidelines and presented our perspectives on refining them to hasten the transition of these drugs from laboratories to market.
1 Citations Source Cite
Published on Dec 1, 2017in Nature Communications 11.88
Iria Gomez-Tourino6
Estimated H-index: 6
(University of Vigo),
Yogesh Kamra1
Estimated H-index: 1
(Guy's Hospital)
+ 2 AuthorsMark Peakman52
Estimated H-index: 52
(NIHR: National Institute for Health Research)
Defects in T cell receptor (TCR) repertoire are proposed to predispose to autoimmunity. Here we show, by analyzing >2 × 108 TCRB sequences of circulating naive, central memory, regulatory and stem cell-like memory CD4+ T cell subsets from patients with type 1 diabetes and healthy donors, that patients have shorter TCRB complementarity-determining region 3s (CDR3), in all cell subsets, introduced by increased deletions/reduced insertions during VDJ rearrangement. High frequency of short CDR3s is ...
6 Citations Source Cite
Published on Dec 1, 2017in Scientific Reports 4.01
Heng Lu2
Estimated H-index: 2
(Paris IV: Paris-Sorbonne University),
Ouriel Caen5
Estimated H-index: 5
(Paris IV: Paris-Sorbonne University)
+ 5 AuthorsValérie Taly25
Estimated H-index: 25
(Paris IV: Paris-Sorbonne University)
Droplet-based microfluidics is extensively and increasingly used for high-throughput single-cell studies. However, the accuracy of the cell counting method directly impacts the robustness of such studies. We describe here a simple and precise method to accurately count a large number of adherent and non-adherent human cells as well as bacteria. Our microfluidic hemocytometer provides statistically relevant data on large populations of cells at a high-throughput, used to characterize cell encapsu...
11 Citations Source Cite
Published on Nov 1, 2017in The Lancet Diabetes & Endocrinology 24.54
Nicholas J Thomas4
Estimated H-index: 4
(University of Exeter),
Samuel E. Jones12
Estimated H-index: 12
(University of Exeter)
+ 3 AuthorsA. T. Hattersley117
Estimated H-index: 117
(University of Exeter)
Summary Background Type 1 diabetes is typically considered a disease of children and young adults. Genetic susceptibility to young-onset type 1 diabetes is well defined and does not predispose to type 2 diabetes. It is not known how frequently genetic susceptibility to type 1 diabetes leads to a diagnosis of diabetes after age 30 years. We aimed to investigate the frequency and phenotype of type 1 diabetes resulting from high genetic susceptibility in the first six decades of life. Methods In th...
48 Citations Source Cite
Cited By1
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Published on May 24, 2019in Diabetes 7.20
Klaus H. Kaestner85
Estimated H-index: 85
(UPenn: University of Pennsylvania),
Alvin C. Powers49
Estimated H-index: 49
(Vandy: Vanderbilt University)
+ 1 AuthorsMark A. Atkinson82
Estimated H-index: 82
(UF: University of Florida)
Type 1 diabetes risk can reliably be predicted by markers of autoimmunity, but approaches to prevent or modify the underlying disease process are needed. We posit this void fundamentally results from a limited understanding of immune-islet cell interactions within the pancreas and relevant immune organs, contributions of β-cells to their own demise, and epigenetic predispositions affecting both immune and islet cells. Because biopsy of the human pancreas and pancreatic lymph nodes carries risk a...
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Published on Jan 1, 2019in The Lancet Diabetes & Endocrinology 24.54
Bart O. Roep58
Estimated H-index: 58
(City of Hope National Medical Center),
Daniel C S Wheeler1
Estimated H-index: 1
('KCL': King's College London),
Mark Peakman52
Estimated H-index: 52
(HealthPartners)
Summary Precision medicine has emerged as a mantra for therapeutic approaches to complex diseases. The defining concept relies on a detailed insight into disease pathogenesis and therapeutic mechanism. Although the type 1 diabetes field has gained new insights into disease endotypes and indications of efficacy for several therapies, none of these is yet licensed, partly because of immune suppressive side-effects beyond control of islet autoimmunity. New strategies designed to regulate the immune...
5 Citations Source Cite