ArticlePloS one2012
Fc gamma receptor CD64 modulates the inhibitory activity of infliximab.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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
28 citing papers in PubMed, 49 citations in OpenAlex.
- Multiple Modes of Action of Anti-TNF-α Antibodies for Inflammatory Bowel Diseases Beyond TNF-α Neutralization.Antibodies (Basel, Switzerland) · 2026Review
- Cardiovascular Adverse Events Associated with Tumor Necrosis Factor-Alpha Inhibitors: A Real-World Pharmacovigilance Analysis.Journal of atherosclerosis and thrombosis · 2024Article
- A Versatile Intestine-on-Chip System for Deciphering the Immunopathogenesis of Inflammatory Bowel Disease.Advanced healthcare materials · 2024Article
- Influence of rheumatoid factor levels and TNF inhibitor structure on secondary nonresponse in rheumatoid arthritis patients.Frontiers in medicine · 2024Article
- Effects of faecal microbiota transplantation on the small intestinal mucosa in systemic sclerosis.Rheumatology (Oxford, England) · 2023Article
- Real world population pharmacokinetic study in children and young adults with inflammatory bowel disease discovers novel blood and stool microbial predictors of vedolizumab clearance.Alimentary pharmacology & therapeutics · 2023Article
- Articular manifestations in patients with inflammatory bowel diseases treated with anti-TNF.RMD open · 2022Article
- Infliximab Can Improve Traumatic Brain Injury by Suppressing the Tumor Necrosis Factor Alpha Pathway.Molecular neurobiology · 2021Review
- Prospective Validation of CD-62L (L-Selectin) as Marker of Durable Response to Infliximab Treatment in Patients With Inflammatory Bowel Disease: A 5-Year Clinical Follow-up.Clinical and translational gastroenterology · 2021Article
- Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease.Pharmaceutics · 2021Article
- The Impact of Obesity on Disease Activity and Treatment Response in Rheumatoid Arthritis.Current rheumatology reports · 2020Review
- Comparison of Adverse Event Profiles of Tumor Necrosis Factor-Alfa Inhibitors: Analysis of a Spontaneous Reporting Database.Therapeutics and clinical risk management · 2020Article
- Elevated Pretreatment Plasma Oncostatin M Is Associated With Poor Biochemical Response to Infliximab.Crohn's & colitis 360 · 2019Article
- Recruitment of activated neutrophils correlates with disease severity in adult Crohn's disease.Clinical and experimental immunology · 2019Article
- Methamphetamine Impairs IgG1-Mediated Phagocytosis and Killing of Cryptococcus neoformans by J774.16 Macrophage- and NR-9640 Microglia-Like Cells.Infection and immunity · 2019Article
- Applicability of Traditional In Vitro Toxicity Tests for Assessing Adverse Effects of Monoclonal Antibodies: A Case Study of Rituximab and Trastuzumab.Antibodies (Basel, Switzerland) · 2018Article
- Surrogate potency assays: Comparison of binding profiles complements dose response curves for unambiguous assessment of relative potencies.Journal of pharmaceutical analysis · 2018Article
- Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis.International journal of molecular sciences · 2018Review
- IVIg and LPS Co-stimulation Induces IL-10 Production by Human Monocytes, Which Is Compromised by an FcγRIIA Disease-Associated Gene Variant.Frontiers in immunology · 2018Article
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Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor necrosis factor (TNF) is an important cytokine in the pathogenesis of inflammatory bowel disease (IBD). Anti-TNF antibodies have been successfully implemented in IBD therapy, however their efficacies differ among IBD patients. Here we investigate the influence of CD64 Fc receptor on the inhibitory activity of anti-TNFs in cells of intestinal wall.
methodsIntestinal cell lines, monocytes/macrophages and peripheral blood mononuclear cells (PBMCs) were used as models. The efficacies of adalimumab, infliximab and certolizumab-pegol were assessed by RT-PCR for target genes. Protein levels and localizations were examined by Western blotting and immunofluorescence. Antibody fragments were obtained by proteolytic digestion, immunoprecipitation and protein chip analysis. Knock-down of specific gene expression was performed using siRNAs.
resultsInfliximab had limited efficacy towards soluble TNF in cell types expressing Fc gamma receptor CD64. Both adalimumab and infliximab had lower efficacies in PBMCs of IBD patients, which express elevated levels of CD64. Infliximab-TNF complexes were more potent in activating CD64 in THP-1 cells than adalimumab, which was accompanied by distinct phospho-tyrosine signals. Blocking Fc parts and isolation of Fab fragments of infliximab improved its efficacy. IFN-γ-induced expression of CD64 correlated with a loss of efficacy of infliximab, whereas reduction of CD64 expression by either siRNA or PMA treatment improved inhibitory activity of this drug. Colonic mRNA expression levels of CD64 and other Fc gamma receptors were significantly increased in the inflamed tissues of infliximab non-responders.
conclusionsCD64 modulates the efficacy of infliximab both in vitro and ex vivo, whereas the presence of this receptor has no impact on the inhibitory activity of certolizumab-pegol, which lacks Fc fragment. These data could be helpful in both predicting and evaluating the outcome of anti-TNF therapy in IBD patients with elevated systemic and local levels of Fc receptors.
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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.