ArticleProceedings of the National Academy of Sciences of the United States of America2008
alpha1-Antitrypsin monotherapy induces immune tolerance during islet allograft transplantation in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03172455 (Early Access Program Using Alpha 1 Antitrypsin Infusion for Patients With Steroid Refractory Acute GvHD After Hematopoietic Stem Cell Transplantation), which is not on this map. Cited by 110 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.
Early Access Program Using Alpha 1 Antitrypsin Infusion for Patients With Steroid Refractory Acute GvHD After Hematopoietic Stem Cell Transplantation (HSCT)
Who cites it
110 citing papers in PubMed, 188 citations in OpenAlex.
- A randomized controlled pilot trial of etanercept and alpha-1 antitrypsin to improve autologous islet engraftment.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2023Trial
- Human plasma-derived alphaPediatric diabetes · 2021Trial
- Biomarker-guided preemption of steroid-refractory graft-versus-host disease with α-1-antitrypsin.Blood advances · 2020Trial
- 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
- Circulating Truncated Alpha-1 Antitrypsin Glycoprotein in Patient Plasma Retains Anti-Inflammatory Capacity.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- αBlood · 2018Trial
- Aspiration, localized pulmonary inflammation, and predictors of early-onset bronchiolitis obliterans syndrome after lung transplantation.Journal of the American College of Surgeons · 2013Trial
- Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study.Cell transplantationTrial
- Polymeric alpha-1 antitrypsin perturbs Paneth cell proteostasis and exacerbates intestinal inflammation.Signal transduction and targeted therapy · 2026Article
- Taming autoimmunity: Alpha-1 antitrypsin overexpressing mesenchymal stromal cells promote regulatory T cell crosstalk to reverse diabetes.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Scaled up fed-batch production of recombinant alpha-1-antitrypsin by CHO cells in single-use surface aerated orbital shaken bioreactor.Scientific reports · 2026Article
- Human Alpha-1 Antitrypsin Suppresses Melanoma Growth by Promoting Tumor Differentiation and CD8Biomolecules · 2026Article
- Chronic obstructive pulmonary disease (COPD) and autoimmune diseases: unravelling complex interactions.Annals of medicine · 2025Review
- Analysis of alpha-1-antitrypsin (AAT)-regulated, glucocorticoid receptor-dependent genes in macrophages reveals a novel host defense function of AAT.Physiological reports · 2024Article
- Proinflammatory Cytokines Suppress Nonsense-Mediated RNA Decay to Impair Regulated Transcript Isoform Processing in Pancreatic β-Cells.bioRxiv : the preprint server for biology · 2024Article
- Proinflammatory cytokines suppress nonsense-mediated RNA decay to impair regulated transcript isoform processing in pancreatic β cells.Frontiers in endocrinology · 2024Article
- Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients.Transplant international : official journal of the European Society for Organ Transplantation · 2024Article
- Beneficial effects of alpha-1 antitrypsin therapy in a mouse model of colitis-associated colon cancer.BMC cancer · 2023Article
- Pancreas Preservation with a Neutrophil Elastase Inhibitor, Alvelestat, Contributes to Improvement of Porcine Islet Isolation and Transplantation.Journal of clinical medicine · 2022Article
- Human placental proteomics and exon variant studies link AAT/SERPINA1 with spontaneous preterm birth.BMC medicine · 2022Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Human pancreatic islet transplantation offers diabetic patients tight glucose control but has low graft survival rates. The immunosuppressive drugs that are administered to graft recipients lack the antiinflammatory benefits of corticosteroids because of their diabetogenic effects. The serum protease inhibitor alpha1-antitrypsin (AAT) possesses antiinflammatory properties and reduces cytokine-mediated islet damage. In the present study, diabetic mice were grafted with allogeneic islets and treated with AAT monotherapy (n = 24). After 14 days of treatment, mice remained normoglycemic and islet allografts were functional for up to 120 treatment-free days. After graft removal and retransplantation, mice accepted same-strain islets but rejected third-strain islets, thus confirming that specific immune tolerance had been induced. Explanted grafts exhibited a population of T regulatory cells in transplant sites. According to RT-PCR, grafts contained high levels of mRNA for foxp3, cytotoxic T lymphocyte antigen-4, TGF-beta, IL-10, and IL-1 receptor antagonist; expression of proinflammatory mediators was low or absent. After implantation of skin allografts, AAT-treated mice had greater numbers of foxp3-positive cells in draining lymph nodes (DLNs) compared with control treatment mice. Moreover, dendritic cells in DLNs exhibited an immature phenotype with decreased CD86 activation marker. Although the number of CD3 transcripts decreased in the DLNs, AAT did not affect IL-2 activity in vitro. Thus, AAT monotherapy provides allografts with antiinflammatory conditions that favor development of antigen-specific T regulatory cells. Because AAT treatment in humans is safe, its use during human islet transplantation may be considered.
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What OpenQuestion holds
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.