ArticleScientific reports2016
Therapeutic TNF Inhibitors can Differentially Stabilize Trimeric TNF by Inhibiting Monomer Exchange.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Serum TNFα levels at 24 h after certolizumab pegol predict effectiveness at week 12 in patients with rheumatoid arthritis from TSUBAME study.Arthritis research & therapy · 2021Trial
- Serum immune profiling suggests overlap between IBD patients with joint complaints and patients with spondyloarthritis.Frontiers in immunology · 2026Article
- The structural basis for the selective antagonism of soluble TNF-alpha by shark variable new antigen receptors.Nature communications · 2025Article
- A Quantitative Approach to Guiding Target Antigen Selection and Antibody Optimization in Recycling Antibody Discovery.The AAPS journal · 2025Article
- MD Simulation Reveals a Trimerization-Enhanced Interaction of CD137L with CD137.International journal of molecular sciences · 2025Article
- Exploring capsaicin as a multi-target agent for osteoporosis through computational insights.In silico pharmacology · 2025Article
- Dynamics of serum levels of TNF-α in a longitudinal follow-up study in 98 patients with juvenile idiopathic arthritis treated with anti-TNF-α biological drugs.Clinical rheumatology · 2024Observational
- Crohn's disease and breast cancer: a literature review of the mechanisms and treatment.Internal and emergency medicine · 2023Review
- Membrane Protein Binding Interactions Studied in Live Cells via Diethylpyrocarbonate Covalent Labeling Mass Spectrometry.Analytical chemistry · 2023Article
- Proteomic analyses do not reveal subclinical inflammation in fatigued patients with clinically quiescent inflammatory bowel disease.Scientific reports · 2022Article
- Biophysical differences in IgG1 Fc-based therapeutics relate to their cellular handling, interaction with FcRn and plasma half-life.Communications biology · 2022Article
- Complementary Structural Information for Antibody-Antigen Complexes from Hydrogen-Deuterium Exchange and Covalent Labeling Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2022Article
- Long-Term Dietary Patterns Are Reflected in the Plasma Inflammatory Proteome of Patients with Inflammatory Bowel Disease.Nutrients · 2022Article
- Trimer-to-Monomer Disruption Mechanism for a Potent, Protease-Resistant Antagonist of Tumor Necrosis Factor-α Signaling.Journal of the American Chemical Society · 2022Article
- The Effect of Phenotype and Genotype on the Plasma Proteome in Patients with Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2022Article
- Epitope Mapping with Diethylpyrocarbonate Covalent Labeling-Mass Spectrometry.Analytical chemistry · 2022Article
- HLAII peptide presentation of infliximab increases when complexed with TNF.Frontiers in immunology · 2022Article
- Infliximab Efficacy May Be Linked to Full TNF-α Blockade in Peripheral Compartment-A Double Central-Peripheral Target-Mediated Drug Disposition (TMDD) Model.Pharmaceutics · 2021Article
- Modulation of the tumor micro-environment by CD8Current opinion in immunology · 2021Review
- Size-based characterization of adalimumab and TNF-α interactions using flow induced dispersion analysis: assessment of avidity-stabilized multiple bound species.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor (TNF) is a homotrimeric cytokine that is a key mediator of inflammation. It is unstable at physiological concentrations and slowly converts into an inactive form. Here, we investigated the mechanism of this process by using a Förster resonance energy transfer (FRET) assay that allowed monitoring of monomeric subunit exchange in time. We observed continuous exchange of monomeric subunits even at concentrations of TNF high enough to maintain its bioactivity. The kinetics of this process closely corresponds with the appearance of monomeric subunits and disappearance of trimeric TNF in time at ng/ml concentrations as monitored by high-performance size-exclusion chromatography (HP-SEC). Furthermore, of the five therapeutic TNF inhibitors that are currently used in the clinic, three (adalimumab, infliximab, etanercept) were found to completely inhibit the monomer exchange reaction and stabilize TNF trimers, whereas golimumab and certolizumab could not prevent monomer exchange, but did slow down the exchange process. These differences were not correlated with the affinities of the TNF inhibitors, measured with both surface plasmon resonance (SPR) and in fluid phase using fluorescence-assisted HP-SEC. The stabilizing effect of these TNF inhibitors might result in prolonged residual TNF bioactivity under conditions of incomplete blocking, as observed in vitro for adalimumab.
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