ArticleJournal of inflammation research2020
Human Neutrophil Elastase Proteolytic Activity in Ulcerative Colitis Favors the Loss of Function of Therapeutic Monoclonal Antibodies.
Article in Journal of inflammation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Neutrophil extracellular traps as a potential therapeutic target in inflammatory bowel disease: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- Transforming growth factor β-activated kinase 1 as a central integrator of immune-microbiota crosstalk in colitis (Review).Experimental and therapeutic medicine · 2026Review
- The Serine Protease-Serine Protease Inhibitor Regulatory Network in Inflammatory Bowel Disease: From Molecular Mechanisms to Novel Therapeutic Horizons.Journal of advanced research · 2026Review
- A Rationally Designed Novel Bifunctional Human TNF-α- and Janus Kinase-Targeted soloMER Drug Conjugate (SDC) with a Neutrophil Elastase Cleavable Linker Delivering Inflammation Site-Specific Release of Payload.Journal of medicinal chemistry · 2026Article
- A chemiluminescence assay targeting granzyme A activity for monitoring inflammatory bowel disease.Nature biomedical engineering · 2026Article
- Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage.Nature biotechnology · 2026Article
- Neutrophil-mediated degradation of type III collagen is elevated in inflammatory bowel disease and DSS-induced colitis reflecting early mucosal damage.Scientific reports · 2025Article
- Neutrophil Elastase and Elafin in Inflammatory Bowel Diseases: Urinary Biomarkers Reflecting Intestinal Barrier Dysfunction and Proteolytic Activity.Journal of clinical medicine · 2025Article
- Pathogenic and Protective Roles of Neutrophils inPathogens (Basel, Switzerland) · 2025Review
- Concentration monitoring and dose optimization for infliximab in Crohn's disease patients: a machine learning-based covariate ensemble model.Frontiers in immunology · 2025Article
- Mechanisms and therapeutic strategies of macrophages and neutrophils inducing ulcerative colitis progression.Frontiers in immunology · 2025Review
- Developing models for the diagnosing of ulcerative colitis and prognosis of anti-TNF-α non-response based on neutrophil extracellular trap-associated genes.Frontiers in immunology · 2025Article
- Crosstalk between neutrophil extracellular traps and gut microbiota in ulcerative colitis: traditional Chinese medicine strategies.Frontiers in cellular and infection microbiology · 2025Review
- Enzymatic, structural, and biophysical characterization of a single-domain antibody (VHH) selectively and tightly inhibiting neutrophil elastase and exhibiting favorable developability properties.Protein science : a publication of the Protein Society · 2024Article
- Intraperitoneal Administration of S100A8 Ameliorates Experimental Acute Colitis in Rats.Biology · 2024Article
- Current understanding of the interplay between extracellular matrix remodelling and gut permeability in health and disease.Cell death discovery · 2024Review
- Neutrophils at the Crossroads: Unraveling the Multifaceted Role in the Tumor Microenvironment.International journal of molecular sciences · 2024Review
- From the bench to the clinic: basophils and type 2 epithelial cytokines of thymic stromal lymphopoietin and IL-33.Clinical & translational immunology · 2024Review
- Blood-Based Biomarkers Reflecting Protease 3 and MMP-12 Catalyzed Elastin Degradation as Potential Noninvasive Surrogate Markers of Endoscopic and Clinical Disease in Inflammatory Bowel Disease.Journal of clinical medicine · 2023Article
- Neutrophils in Inflammatory Diseases: Unraveling the Impact of Their Derived Molecules and Heterogeneity.Cells · 2023Review
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
No grant is acknowledged in the PubMed record.
Abstract
purposeProteases play an essential role in the pathophysiology of inflammatory bowel disease (IBD), contributing to the intestinal mucosal lesions through the degradation of the extracellular matrix and alteration of the barrier function. Ulcerative colitis (UC) is characterized by an extensive infiltrate of neutrophils into the mucosa and hence, increased proteolytic activity. Human neutrophil elastase (HNE) is a serine protease that has been reported to be increased in UC patients' intestinal mucosa. Based on our previous studies, we hypothesized that HNE might induce proteolytic degradation and loss of function of therapeutic monoclonal antibodies in IBD patients. PATIENTS AND
methodsElastase expression and elastinolytic activity were determined in mucosal explants from ulcerative colitis patients (n=6) and cultured ex vivo in the presence or absence of recombinant elafin. Enzymatic digestions of therapeutic monoclonal antibodies were performed using recombinant HNE and elafin. The integrity of the therapeutic antibodies was evaluated by immunoblotting and protein G binding assay, whereas their TNF-neutralizing activity was assessed with a reporter cell line.
resultsWe found that HNE and its elastinolytic activity were increased in the gut mucosa of UC patients. We also demonstrated that HNE cleaved biological drugs, impairing the TNF-α neutralizing capacity of anti-TNF monoclonal antibodies. This proteolytic degradation was inhibited by the addition of the specific inhibitor, elafin.
conclusionOur results suggest that the high level of proteolytic degradation by mucosal neutrophil elastase, along with a potential imbalance with elafin, contributes to the loss of function of biologic agents, which are currently used in patients with IBD. These findings might explain the non-responsiveness of UC patients to therapeutic monoclonal antibodies and suggest the potential beneficial concomitant use of elafin in this treatment.
Indexed as
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.