ArticleThe Journal of clinical endocrinology and metabolism2014
α1-Antitrypsin therapy downregulates toll-like receptor-induced IL-1β responses in monocytes and myeloid dendritic cells and may improve islet function in recently diagnosed patients with type 1 diabetes.
Article in The Journal of clinical endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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
38 citing papers in PubMed, 63 citations in OpenAlex.
- Human plasma-derived alphaPediatric diabetes · 2021Trial
- A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (GlassiaInternational journal of molecular sciences · 2019Trial
- Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study.Cell transplantationTrial
- Dendritic Cells as Immunometabolic Regulatory Nodes in Diabetes: Molecular Mechanisms and Therapeutic Reprogramming.International journal of molecular sciences · 2026Review
- Altered Serum Alpha1-Antitrypsin Protease Inhibition before and after Clinical Hematopoietic Stem Cell Transplantation: Association with Risk for Non-Relapse Mortality.International journal of molecular sciences · 2023Article
- Loss ofInternational journal of molecular sciences · 2022Article
- Exosome Proteomics Reveals the Deregulation of Coagulation, Complement and Lipid Metabolism Proteins in Gestational Diabetes Mellitus.Molecules (Basel, Switzerland) · 2022Article
- Mechanisms Linking COPD to Type 1 and 2 Diabetes Mellitus: Is There a Relationship between Diabetes and COPD?Medicina (Kaunas, Lithuania) · 2022Review
- Comparison of alpha 1- antitrypsin activity and phenotype in type 1 diabetic patients to healthy individuals.Journal of family medicine and primary care · 2022Article
- The Role of Proteases and Serpin Protease Inhibitors in β-Cell Biology and Diabetes.Biomolecules · 2022Review
- Therapeutic benefits of recombinant alpha1-antitrypsin IgG1 Fc-fusion protein in experimental emphysema.Respiratory research · 2021Article
- Therapeutic Potential of Alpha-1 Antitrypsin in Type 1 and Type 2 Diabetes Mellitus.Medicina (Kaunas, Lithuania) · 2021Review
- The Impact of the CaBiomolecules · 2021Review
- Association between α1-antitrypsin and acute coronary syndrome.Experimental and therapeutic medicine · 2020Article
- Mechanisms behind Retinal Ganglion Cell Loss in Diabetes and Therapeutic Approach.International journal of molecular sciences · 2020Review
- The Delivery of α1-Antitrypsin Therapy Through Transepidermal Route: Worthwhile to Explore.Frontiers in pharmacology · 2020Article
- Targeting innate immune mediators in type 1 and type 2 diabetes.Nature reviews. Immunology · 2019Review
- Vitamin D (1,25(OH)The Journal of steroid biochemistry and molecular biology · 2019Article
- The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives.European cardiology · 2019Review
- S-Nitrosylation of α1-Antitrypsin Triggers Macrophages Toward Inflammatory Phenotype and Enhances Intra-Cellular Bacteria Elimination.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
contextRecent studies have implicated proinflammatory responses in the mechanism of type 1 diabetes (T1D).
objectiveOur objective was to evaluate the safety and effects of therapy with the anti-inflammatory serum protein α1-antitrypsin (AAT) on islet function and innate immunity in recent-onset patients. DESIGN AND
settingThis was an open-label phase I trial at the Barbara Davis Center for Childhood Diabetes, University of Colorado Denver. PATIENTS: Twelve recently diagnosed subjects with T1D with detectable C-peptides were included in the study.
interventionEight consecutive weekly infusions of 80 mg/kg of AAT were given.
main outcome measuresPATIENTS were monitored for adverse effects of AAT therapy, C-peptide responses to a mixed-meal tolerance test, and toll-like receptor (TLR)-induced cellular IL-1β in monocytes and myeloid dendritic cells (mDCs).
resultsNo adverse effects were detected. AAT led to increased, unchanged, or moderately reduced levels of C-peptide responses compared with baseline in 5 patients. The total content of TLR4-induced cellular IL-1β in monocytes at 12 months after AAT therapy was 3-fold reduced compared with baseline (P < .05). Furthermore, at baseline, 82% of monocytes produced IL-1β, but at 12 months after therapy, the level decreased to 42%. Similar reductions were observed using TLR7/8 and TLR3 agonists in monocytes and mDCs. Unexpectedly, the reduction in cellular IL-1β was observed only 9 and 12 months after treatment but not in untreated diabetics. Improved β-cell function in the 5 AAT-treated individuals correlated with lower frequencies of monocytes and mDCs producing IL-1β compared with subjects without improvement of islet function (P < .04 and P < .02, respectively).
conclusionsWe hypothesize that AAT may have a beneficial effect on T1D in recently diagnosed patients that is associated with downmodulation of IL-1β.
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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.