ArticleProceedings of the National Academy of Sciences of the United States of America2012
Alpha-1-antitrypsin monotherapy reduces graft-versus-host disease after experimental allogeneic bone marrow transplantation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 134 citations in OpenAlex.
- 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
- αBlood · 2018Trial
- Alpha 1 Antitrypsin Suppresses Autoantibody Production and Cellular Autoimmunity in Chronic Graft-Versus-Host Disease (cGVHD) in a Lupus Mouse Model.Biomolecules · 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
- The Role of Alpha-1 Antitrypsin in the Pathophysiology and Treatment of Inflammatory Lung Diseases.Journal of inflammation research · 2026Review
- New age GVHD prophylaxis regimens: what works for what donor and why.Hematology. American Society of Hematology. Education Program · 2025Review
- SERPINA1 gene regulates the tumorigenesis and progression of breast cancer through PI3K/AKT signaling pathway and tumor immune microenvironment.Scientific reports · 2025Article
- α‑1 Antitrypsin is a potential target of inflammation and immunomodulation (Review).Molecular medicine reports · 2025Review
- Graft-Versus-Host Disease Mouse Models: A Clinical-Translational Perspective.Methods in molecular biology (Clifton, N.J.) · 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
- Immunological and homeostatic pathways of alpha -1 antitrypsin: a new therapeutic potential.Frontiers in immunology · 2024Review
- 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
- Beneficial effects of alpha-1 antitrypsin therapy in a mouse model of colitis-associated colon cancer.BMC cancer · 2023Article
- Serpin Family A Member 1 Is Prognostic and Involved in Immunological Regulation in Human Cancers.International journal of molecular sciences · 2023Article
- Alpha-1-Antitrypsin Experience for Steroid-Resistant Acute Graft-Versus-Host Disease.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2022Article
- Improved outcome of patients with graft-versus-host disease after allogeneic hematopoietic cell transplantation for hematologic malignancies over time: an EBMT mega-file study.Haematologica · 2022Article
- Drugs and biologics receiving FDA orphan drug designation: an analysis of the most frequently designated products and their repositioning strategies.Expert opinion on orphan drugs · 2022Article
- Immune Suppression in Allogeneic Hematopoietic Stem Cell Transplantation.Handbook of experimental pharmacology · 2022Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Acute graft-versus-host disease (GvHD) is a major complication that prevents successful outcomes after allogeneic bone marrow transplantation (BMT), an effective therapy for hematological malignancies. Several studies demonstrate that donor T cells and host antigen-presenting cells along with several proinflammatory cytokines are required for the induction of GvHD and contribute to its severity. Increasing evidence demonstrates that human serum-derived αalpha-1- anti-trypsin (AAT) reduces production of proinflammatory cytokines, induces anti-inflammatory cytokines, and interferes with maturation of dendritic cells. Using well-characterized mouse models of BMT, we have studied the effects of AAT on GvHD severity. Administration of AAT early after BMT decreased mortality in three models of GvHD and reduced serum levels of proinflammatory cytokines in the allogeneic recipients compared with vehicle (albumin) treated animals. AAT treatment reduced the expansion of alloreactive T effector cells but enhanced the recovery of T regulatory T cells, (Tregs) thus altering the ratio of donor T effector to T regulatory cells in favor of reducing the pathological process. However, despite altering the ratio in vivo, AAT had no direct effects on either the donor T effector cells or T regulatory cells Tregs in vitro. In contrast, AAT suppressed LPS-induced in vitro secretion of proinflammatory cytokines such as TNF-α and IL-1β, enhanced the production of the anti-inflammatory cytokine IL-10, and impaired NF-κB translocation in the host dendritic cells. In light of its long history of safety in humans, these findings suggest that administration of AAT represents a novel unique and viable strategy to mitigate clinical GvHD.
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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.