ArticleThe Journal of clinical investigation2024
Thrombotic microangiopathy following systemic AAV administration is dependent on anti-capsid antibodies.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Incidence, timing, and clinical significance of adverse immune events after gene replacement therapy: A systematic review and meta-analysis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- First-in-human nuclease-free homologous recombination-dependent gene editing in pediatric patients with methylmalonic acidemia: results of a phase 1/2 study.Gene therapy · 2026Trial
- Clinical immunogenicity in rAAV gene therapy: Insights and implications.Molecular therapy. Advances · 2026Review
- Automated zonal-rotor CsCl ultracentrifugation with ÄKTA-based fractionation removes empty and intermediate AAV capsids.Molecular therapy. Advances · 2026Article
- Host Endoplasmic Reticulum Stress and Interferon Responses Contribute to AAV-Induced Ocular Toxicity.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial Quality Control in Inherited Mitochondrial Cardiomyopathy: Convergent Pathobiology and a Testable Therapeutic Framework.International journal of molecular sciences · 2026Review
- Next generation AAV-F capsid gene therapy rescues disease pathology in a model of pyruvate dehydrogenase complex deficiency.Molecular therapy. Advances · 2026Article
- Immunogenicity in Approved Adeno-Associated Virus-Based Gene Therapies: A Framework for a Tailored Assessment Strategy.The AAPS journal · 2026Review
- Recent advancements in improving cross-species applicability of bioengineered AAV capsids.Gene therapy · 2026Review
- Cancer cell-selective ectopic expression of CD20 as an antigen enables rituximab repurposing for solid tumour immunotherapy.Clinical and translational medicine · 2026Article
- Transplantation as disease modifying therapy in the era of gene therapy medicinal products - health policy considerations.Orphanet journal of rare diseases · 2026Review
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Preclinical pharmacology and toxicology study of an AAV8-tATP7B vector for Wilson's disease.Clinical and molecular hepatology · 2026Article
- Transient prophylactic immunosuppression with abatacept or dasatinib prevents immune responses in AAV gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Taming immune responses to AAV gene therapy by programmed in vivo Treg expansion.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Safety of Adeno-Associated Viral Vectors in Gene Therapy: Mechanisms of Toxicity, Clinical Risks, and Strategies for Their Minimization.International journal of molecular sciences · 2026Review
- Single nuclei/cell transcriptomics reveal DMD driven cell dynamics and mechanisms of fibroblast inflammatory tissue priming in human dystrophic muscle.Research square · 2026Article
- Deaths in gene therapy of Duchenne muscular dystrophy and other diseases: Underlying mechanisms and mitigating strategies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Immune Toxicities in AAV Gene Therapy: Overview for Clinicians.International journal of molecular sciences · 2026Review
- Sirolimus for the treatment of steroid-refractory hepatotoxicity following AAV gene therapy in patients with Duchenne muscular dystrophy.Journal of neuromuscular diseases · 2026Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
BACKGROUNDSystemic administration of adeno-associated virus (AAV) can trigger life-threatening inflammatory responses, including thrombotic microangiopathy (TMA), acute kidney injury due to atypical hemolytic uremic syndrome-like complement activation, immune-mediated myocardial inflammation, and hepatic toxicity.METHODSWe describe the kinetics of immune activation following systemic AAV serotype 9 (AAV9) administration in 38 individuals following 2 distinct prophylactic immunomodulation regimens. Group 1 received corticosteroids and Group 2 received rituximab plus sirolimus in addition to steroids to prevent anti-AAV antibody formation.RESULTSGroup 1 participants had a rapid increase in immunoglobulin M (IgM) and IgG. Increase in D-dimer, decline in platelet count, and complement activation are indicative of TMA. All Group 1 participants demonstrated activation of both classical and alternative complement pathways, as indicated by depleted C4 and elevated soluble C5b-9, Ba, and Bb antigens. Group 2 patients did not have a significant change in IgM or IgG and had minimal complement activation.CONCLUSIONSThis study demonstrates that TMA in the setting of AAV gene therapy is antibody dependent (classical pathway) and amplified by the alternative complement pathway. Critical time points and interventions are identified to allow for management of immune-mediated events that impact the safety and efficacy of systemic gene therapy.
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Identifiers
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.