ArticleJCI insight2020
Local complement activation is associated with primary graft dysfunction after lung transplantation.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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.
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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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Risk factors for pulmonary complications in systemic lupus erythematosus: a meta-analysis of infectious pneumonia and interstitial lung disease.Frontiers in immunology · 2026Pooled it
- Review
- Chronic TGFβ1 Signaling Drives Aberrant Alveolar-Basaloid Metaplasia through a KRT17-Stratifin migratory complex.bioRxiv : the preprint server for biology · 2026Article
- Evaluation of ventilation at 10 °C as the optimal storage condition for donor lungs in a murine model.Scientific reports · 2026Article
- Immune complex handling in transplantation: central roles for complement factor H, animal models, and translational implications.Frontiers in immunology · 2026Review
- Donor-size-normalized tidal volume and early peak airway pressure-derived pressure burden after lung transplantation: an exploratory single-center cohort study.Frontiers in medicine · 2026Article
- The Myeloid-T Lymphocyte Axis in Chronic Lung Allograft Rejection: Emerging Insights into the Immune Circuitry Driving Fibrosis.Results and problems in cell differentiation · 2026Review
- Lung Ischemia-Reperfusion Injury in Lung Transplant Surgery: Where Do We Stand?Antioxidants (Basel, Switzerland) · 2025Review
- Emerging roles for complement in lung transplantation.The Journal of clinical investigation · 2025Review
- Primary Graft Dysfunction in Lung Transplantation: An Overview of the Molecular Mechanisms.International journal of molecular sciences · 2025Review
- Lung rehabilitation using xenogeneic cross-circulation does not lead to hyperacute rejection in a human lung transplantation model.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2025Article
- Ex vivo lung perfusion with GLP-1R agonist mitigates ischemia/reperfusion injury through pyroptosis modulation in lung transplantation- an experimental study.International journal of surgery (London, England) · 2025Article
- Primary graft dysfunction after Lung transplantation: unveiling the role of innate immunity.Clinical and experimental immunology · 2025Article
- An injury-induced mesenchymal-epithelial cell niche coordinates regenerative responses in the lung.Science (New York, N.Y.) · 2024Article
- Local complement activation and modulation in mucosal immunity.Mucosal immunology · 2024Review
- Development and validation of primary graft dysfunction predictive algorithm for lung transplant candidates.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2024Article
- Temporal correlation between postreperfusion complement deposition and severe primary graft dysfunction in lung allografts.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2024Article
- The Role of Ficolins in Lung Injury.Journal of innate immunity · 2024Review
- Resolvin D1 prevents injurious neutrophil swarming in transplanted lungs.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- New Aspects of Lung Transplantation: A Narrative Overview Covering Important Aspects of Perioperative Management.Life (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUNDThe complement system plays a key role in host defense but is activated by ischemia/reperfusion injury (IRI). Primary graft dysfunction (PGD) is a form of acute lung injury occurring predominantly due to IRI, which worsens survival after lung transplantation (LTx). Local complement activation is associated with acute lung injury, but whether it is more reflective of allograft injury compared with systemic activation remains unclear. We proposed that local complement activation would help identify those who develop PGD after LTx. We also aimed to identify which complement activation pathways are associated with PGD.METHODSWe performed a multicenter cohort study at the University of Pennsylvania and Washington University School of Medicine. Bronchoalveolar lavage (BAL) and plasma specimens were obtained from recipients within 24 hours after LTx. PGD was scored based on the consensus definition. Complement activation products and components of each arm of the complement cascade were measured using ELISA.RESULTSIn both cohorts, sC4d and sC5b-9 levels were increased in BAL of subjects with PGD compared with those without PGD. Subjects with PGD also had higher C1q, C2, C4, and C4b, compared with subjects without PGD, suggesting classical and lectin pathway involvement. Ba levels were higher in subjects with PGD, suggesting alternative pathway activation. Among lectin pathway-specific components, MBL and FCN-3 had a moderate-to-strong correlation with the terminal complement complex in the BAL but not in the plasma.CONCLUSIONComplement activation fragments are detected in the BAL within 24 hours after LTx. Components of all 3 pathways are locally increased in subjects with PGD. Our findings create a precedent for investigating complement-targeted therapeutics to mitigate PGD.FUNDINGThis research was supported by the NIH, American Lung Association, Children's Discovery Institute, Robert Wood Johnson Foundation, Cystic Fibrosis Foundation, Barnes-Jewish Hospital Foundation, Danish Heart Foundation, Danish Research Foundation of Independent Research, Svend Andersen Research Foundation, and Novo Nordisk Research Foundation.
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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.