Abstract
ObjectiveTo explore proteins associated with ankylosing spondylitis (AS) and to investigate potential proteins that may predict treatment response of adalimumab (ADA) in AS patients.MethodsIn the discovery cohort, 39 AS patients and 20 healthy controls (HCs) were included, and 16 AS patients received ADA treatment for 24 weeks after included. In the validation cohort, 43 AS patients and 39 HCs were enrolled, and all 43 patients received ADA treatment after enrollment. Blood samples and clinical information were collected from two cohorts at baseline from all participants and week 24 from patients received ADA treatment. A human antibody array containing 1,000 proteins was used in the discovery phase, and Elisa kits were used for protein validation.ResultsCompared with HCs, we identified 53 differentially expressed proteins (DEPs) in AS patients. Bioinformatics analysis revealed they were mostly enriched in coagulation function-related pathways, acute response signaling, and LXR/RXR activation. Bone metabolism pathways were also associated. Comparison between samples of pre- and post-ADA treatment revealed 42 DEPs. They were mostly associated with bone metabolism and inflammation response pathways. Significant enrichment was also found in LXR/RXR activation but not the coagulation function-related pathways. Upstream regulator analysis suggested that most regulators also significantly functioned under usage of ADA. Precisely, seven proteins were abnormally expressed in AS and restored after ADA treatment. Retinol-binding protein 4 (RBP4), one of the seven proteins, was validated that its baseline levels were inversely correlated with improvements in Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP). Likewise, percentage changes in RBP4 levels were inversely correlated with changes in ASDAS-CRP score.ConclusionA dysregulated serum protein profile existed in AS. ADA exerted a considerable but not entire alteration toward the dysregulation. RBP4 could be a biomarker for predicting and monitoring ADA treatment response.
Highlights
MATERIALS AND METHODSAnkylosing spondylitis (AS), a subset of axial spondyloarthritis (SpA), is a chronic inflammatory disorder with a predilection for the axial skeleton, characterized by sacroiliitis, uveitis, enthesitis, and spinal inflammation
To optimize the use of ADA treatment, we aimed to find out proteins that could serve as biomarkers for predicting and monitoring treatment response in AND METHODSAnkylosing spondylitis (AS) patients
After adjustment for gender, age, and disease duration, from baseline to week 12, percentage changes in retinol-binding protein 4 (RBP4) levels were inversely correlated with changes in ASDAS-C-reactive protein (CRP) scores (r = 0.547, P < 0.001)
Summary
MATERIALS AND METHODSAnkylosing spondylitis (AS), a subset of axial spondyloarthritis (SpA), is a chronic inflammatory disorder with a predilection for the axial skeleton, characterized by sacroiliitis, uveitis, enthesitis, and spinal inflammation. In the past two decades, the introduction of tumor necrosis factor (TNF) α inhibitors has dramatically improved the treatment of AS, especially in patients with insufficient response to conventional therapy. Adalimumab (ADA), a fully humanized monoclonal antibody against TNF-α, can reduce symptoms and signs of the disease and diminish magnetic resonance imaging-detectable inflammation in the sacroiliac joints and spine. Despite the effect on controlling joint inflammation, whether ADA or other TNF inhibitors can inhibit radiographic progression is still controversial (Molnar et al, 2018). Approximately 40% of patients treated with TNFα inhibitor therapy fail to achieve favorable clinical improvement (Sieper and Poddubnyy, 2017). Given the uncertainty of therapeutic effects and high costs, it is essential to identify biomarkers for predicting and monitoring the response of ADA treatment
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