An explorative study on deep profiling of peripheral leukocytes to identify predictors for responsiveness to anti-tumour necrosis factor alpha therapies in ankylosing spondylitis: natural killer cells in focus

Arthritis Research & Therapy
Ursula Schulte-WredeAndreas Grützkau

Abstract

Therapeutic targeting of tumour necrosis factor (TNF)-α is highly effective in ankylosing spondylitis (AS) patients. However, since one-third of anti-TNF-treated AS patients do not show an adequate clinical response there is an urgent need for new biomarkers that would aid clinicians in their decision-making to select appropriate therapeutic options. Thus, the aim of this explorative study was to identify cell-based biomarkers in peripheral blood that could be used for a pre-treatment stratification of AS patients. A high-dimensional, multi-parametric flow cytometric approach was applied to identify baseline predictors in 31 AS patients before treatment with the TNF blockers adalimumab (TNF-neutralisation) and etanercept (soluble TNF receptor). As the major result, the frequencies of natural killer (NK) cells, and in particular CD8-positive (CD8+) NK cell subsets, were most predictive for therapeutic outcome in AS patients. While an inverse correlation between classical CD56+/CD16+ NK cells and reduction of disease activity was observed, the CD8+ NK cell subset behaved in the opposite direction. At baseline, responders showed significantly increased frequencies of CD8+ NK cells compared with non-responders. This is the first st...Continue Reading

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Citations

Dec 10, 2020·Science Signaling·Heather TorreyDenise L Faustman
Feb 25, 2021·Expert Review of Clinical Immunology·Ikram MezghicheElisabetta Bianchi
Mar 16, 2021·Frontiers in Immunology·Umut Can KucuksezerGunnur Deniz
Aug 26, 2021·Expert Opinion on Therapeutic Targets·Bilade CherqaouiMaxime Breban

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Methods Mentioned

BETA
ESR
flow cytometry
FCS

Software Mentioned

Prism
GraphPad
FACSDIVA
Access
immunoClust

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