Related Experiment Video
Updated: Jun 16, 2026

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method
Published on: September 16, 2017
Transcriptional immune programs underlying inadequate response to tumor necrosis factor inhibitors in ankylosing
Chia-Chun Tseng1, Chang-Yi Yen2, Chih-Yun Pai3
1Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Abstract:
Inadequate response to tumor necrosis factor inhibitors (TNFi) in ankylosing spondylitis (AS) remains common. As the immunoregulatory and immunometabolic alterations across TNFi inadequate responder (TNFi-IR) subsets remain unexplored, we characterized molecular profiles across distinct immune subsets in TNFi-IRs and identified signatures linked to TNFi-IR. We compared subset-specific expression in 16 TNFi-IRs and 13 TNFi responders (TNFi-Rs). Gene expression demonstrated fair-good discriminative power (area under the curve: 0.70-0.87). TNFi-IRs displayed distinct transcriptomic profiles and aberrant transcription factor activity amplifying inflammatory responses across immune subsets. Pathway analysis revealed synergistic association between immune subsets and inadequate response, with recurrent alterations in mitochondrial respiration accompanied by metabolic reprogramming exacerbating immune activation. Altered cell-cell communication hinted at impaired IL-10 and IL-19 regulatory signaling. We identified candidates with repurposing potential for TNFi-IRs. These findings reveal crucial therapeutic targets spanning genes, transcription factors, pathways, metabolites, and cell-cell communication signaling for bench-to-bedside investigation.
Related Concept Videos
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammatory Bowel Disease III: Crohn's Disease
Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...