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Arthritis Res Ther. 2018 Aug 29;20(1):191. doi: 10.1186/s13075-018-1692-y.

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.

Author information

1
German Rheumatism Research Center Berlin (DRFZ), an Institute of the Leibniz-Association, Immune Monitoring Core Facility, Charitéplatz 1, 10117, Berlin, Germany.
2
Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
3
German Rheumatism Research Center Berlin (DRFZ), an Institute of the Leibniz-Association, Bioinformatics Group, Berlin, Germany.
4
Department of Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
5
German Rheumatism Research Center Berlin (DRFZ), an Institute of the Leibniz-Association, Cell Biology Group, Berlin, Germany.
6
German Rheumatism Research Center Berlin (DRFZ), an Institute of the Leibniz-Association, Epidemiology Unit, Berlin, Germany.
7
German Rheumatism Research Center Berlin (DRFZ), an Institute of the Leibniz-Association, Immune Monitoring Core Facility, Charitéplatz 1, 10117, Berlin, Germany. gruetzkau@drfz.de.

Abstract

BACKGROUND:

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.

METHODS:

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).

RESULTS:

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.

CONCLUSIONS:

This is the first study demonstrating that the composition of the NK cell compartment has predictive power for prediction of therapeutic outcome for anti-TNF-α blockers, and we identified CD8+ NK cells as a potential new player in the TNF-α-driven chronic inflammatory immune response of AS.

KEYWORDS:

Ankylosing spondylitis; CD8+ NK cells; Etanercept; Predictive biomarker; TNF-alpha blocker

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