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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.    Electronic supplementary material  The online version of this article (10.1186/s13075-018-1692-y) contains supplementary material, which is available to authorized users.

arthritis research and therapy

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