Background Therapeutic targeting of TNF is approved to be highly effective in ankylosing spondylitis patients who fail to respond to conventional anti-inflammatory drugs. However, only around two-thirds of anti-TNFa treated AS patients show an adequate response according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) independently from the biological used. Therefore, there is an urgent need for biomarkers which would aid in treatment choice and treatment outcome separating responders and non-responders to such expensive therapies and to avoid side effects induced by inefficient drugs. Thus, the aim of this study was to identify cell-based biosensors in peripheral blood by multiparametric flow cytometry that can be used for an early treatment stratification of AS patients.
Methods A multiparametric flow cytometric approach, including 50 monoclonal antibodies combined to 10 staining cocktails, was applied to identify useful baseline predictors in 38 AS patients with active disease before treatment with the TNF blocker Adalimumab, Etanercept, Golimumab or Infliximab. BASDAI response criteria were used to determine therapeutic success after 1 to 6 month. Automated clustering of flow data, correlation analysis and receiver operator characteristics were accomplished to appoint auspicious candidate phenotypes.
Results Out of multiple potentially significant parameters, which are involved both in acquired and adaptive immunity the NK cell compartment revealed most promising subsets that are predictive for a successful therapy response to Etanercept in AS. Correlation analyses showed an error-free classification of responders and non-responders for Etanercept but not for Adalimumab-treated patients.
Conclusions This is the first study demonstrating that the composition of the NK cell compartment has predictive power with respect to classify AS patients whether they will respond or fail to the treatment by Etanercept. These results also shed some new light on the mode of action comparing TNF-alpha neutralising antibodies and soluble TNF alpha-receptors. In conclusion, these data make it reasonable to assume that monitoring of particular NK cell phenotypes can be used in terms of a companion diagnostic to realise the concept of personalised medicine in the field of rheumatology.
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