ArticleDiabetes2012
Preexisting autoantibodies predict efficacy of oral insulin to cure autoimmune diabetes in combination with anti-CD3.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Preexisting insulin autoantibodies predict efficacy of otelixizumab in preserving residual β-cell function in recent-onset type 1 diabetes.Diabetes care · 2015Trial
- Plasmid-encoded proinsulin preserves C-peptide while specifically reducing proinsulin-specific CD8⁺ T cells in type 1 diabetes.Science translational medicine · 2013Trial
- Article
- Type 1 diabetes mellitus and its oral tolerance therapy.World journal of diabetes · 2020Review
- Applications of Quantitative Systems Pharmacology in Model-Informed Drug Discovery: Perspective on Impact and Opportunities.CPT: pharmacometrics & systems pharmacology · 2019Article
- A future for CD3 antibodies in immunotherapy of type 1 diabetes.Diabetologia · 2019Article
- Oral Administration of Silkworm-Produced GAD65 and Insulin Bi-Autoantigens against Type 1 Diabetes.PloS one · 2016Article
- In silico model-based inference: an emerging approach for inverse problems in engineering better medicines.Current opinion in chemical engineering · 2015Article
- Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis.The Journal of clinical endocrinology and metabolism · 2015Article
- Enhancing the discovery and development of immunotherapies for cancer using quantitative and systems pharmacology: Interleukin-12 as a case study.Journal for immunotherapy of cancer · 2015Review
- Modeling the T cell immune response: a fascinating challenge.Journal of pharmacokinetics and pharmacodynamics · 2014Review
- Metabolic syndrome - Removing roadblocks to therapy: Antigenic immunotherapies.Molecular metabolism · 2014Review
- Combination therapy with an anti-IL-1β antibody and GAD65 DNA vaccine can reverse recent-onset diabetes in the RIP-GP mouse model.Diabetes · 2014Article
- Non-antigenic and antigenic interventions in type 1 diabetes.Human vaccines & immunotherapeutics · 2014Review
- Trials in type 1 diabetes: Antigen-specific therapies.Clinical immunology (Orlando, Fla.) · 2013Review
- Clinical optimization of antigen specific modulation of type 1 diabetes with the plasmid DNA platform.Clinical immunology (Orlando, Fla.) · 2013Review
- Antigen-based vaccination and prevention of type 1 diabetes.Current diabetes reports · 2013Review
- Nonviral delivery of small interfering RNA into pancreas-associated immune cells prevents autoimmune diabetes.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- IL-7 receptor α blockade, an off-switch for autoreactive T cells.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Animal models of diabetes mellitus for islet transplantation.Experimental diabetes research · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously developed a combination therapy (CT) using anti-CD3 monoclonal antibodies together with islet-(auto)antigen immunizations that can more efficiently reverse type 1 diabetes (T1D) than either entity alone. However, clinical translation of antigen-specific therapies in general is hampered by the lack of biomarkers that could be used to optimize the modalities of antigen delivery and to predict responders from nonresponders. To support the rapid identification of candidate biomarkers, we systematically evaluated multiple variables in a mathematical disease model. The in silico predictions were validated by subsequent laboratory data in NOD mice with T1D that received anti-CD3/oral insulin CT. Our study shows that higher anti-insulin autoantibody levels at diagnosis can distinguish responders and nonresponders among recipients of CT exquisitely well. In addition, early posttreatment changes in proinflammatory cytokines were indicative of long-term remission. Coadministration of oral insulin improved and prolonged the therapeutic efficacy of anti-CD3 therapy, and long-term protection was achieved by maintaining elevated insulin-specific regulatory T cell numbers that efficiently lowered diabetogenic effector memory T cells. Our validation of preexisting autoantibodies as biomarkers to distinguish future responders from nonresponders among recipients of oral insulin provides a compelling and mechanistic rationale to more rapidly translate anti-CD3/oral insulin CT for human T1D.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.