Abstract
BackgroundTumor necrosis factor (TNF) blockers have a high efficacy in treating Ankylosing Spondylitis (AS), yet up to 40% of AS patients show poor or even no response to this treatment. In this paper, we aim to build an approach to predict the response prior to clinical treatment.MethodsAS patients during the active progression were included and treated with TNF blocker for 3 months. Patients who do not fulfill ASASAS40 were considered as poor responders. The Immunoglobulin G galactosylation (IgG-Gal) ratio representing the quantity of IgG galactosylation was calculated and candidate single nucleotide polymorphisms (SNPs) in patients treated with etanercept was obtained. Machine-learning models and cross-validation were conducted to predict responsiveness.ResultsBoth IgG-Gal ratio at each time point and differential IgG-Gal ratios between week 0 and weeks 2, 4, 8, 12 showed significant difference between responders and poor-responders. Area under curve (AUC) of the IgG-Gal ratio prediction model was 0.8 after cross-validation, significantly higher than current clinical indexes (C-reactive protein (CRP) = 0.65, erythrocyte sedimentation rate (ESR) = 0.59). The SNP MYOM2-rs2294066 was found to be significantly associated with responsiveness of etanercept treatment. A three-stage approach consisting of baseline IgG-Gal ratio, differential IgG-Gal ratio in 2 weeks, and rs2294066 genotype demonstrated the ability to precisely predict the response of anti-TNF therapy (100% for poor-responders, 98% for responders).ConclusionsCombination of different omics can more precisely to predict the response of TNF blocker and it is potential to be applied clinically in the future.
Highlights
Ankylosing spondylitis (AS) is an immune-mediated inflammatory disorder of the spine and sacroiliac joints, which could lead to vertebral fusion (Taurog et al, 2016)
Detection of Immunoglobulin G (IgG) galactosylation ratio (IgG-gal ratio) Immunoglobulin G galactosylation (IgG-Gal) ratio was detected by the method reported in our previous study
IgG-gal ratio is significantly different between responders and poor-responders Etanercept is the most widely used type of Tumor necrosis factor (TNF) blocker for Ankylosing Spondylitis (AS) patients in China
Summary
Ankylosing spondylitis (AS) is an immune-mediated inflammatory disorder of the spine and sacroiliac joints, which could lead to vertebral fusion (Taurog et al, 2016). While the annual cost of TNF-blockers is large, up to 40% of AS patients have no or poor response to this treatment (Schabert et al, 2013; Sieper & Poddubnyy, 2017). It is essential to find biomarkers to predict the responsiveness of TNF blockers in clinical practice, preferably before or at the start of TNF blocker treatment. Multiple studies have examined associations of genetic biomarkers, especially TNFA promoter polymorphisms, with responsiveness to TNF blocker treatment (Tong et al, 2012; Song et al, 2015; Tong et al, 2013; Liu et al, 2016). Tumor necrosis factor (TNF) blockers have a high efficacy in treating Ankylosing Spondylitis (AS), yet up to 40% of AS patients show poor or even no response to this treatment. We aim to build an approach to predict the response prior to clinical treatment
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