Bruton's Tyrosine Kinase in Ankylosing Spondylitis

Abstract

Study design: Prospective case-control study.

Objective: To explore the role of Bruton's tyrosine kinase (BTK) in ankylosing spondylitis (AS).

Summary of background data: AS substantially affects patients, impairing the range of motion in the whole spine and peripheral joints, as well as overall quality of life. However, surveillance for this condition is limited, and biomarkers that can predict disease activity are not well documented.

Patients and methods: The expression of the BTK gene in peripheral blood mononuclear cells (PBMCs) was measured using flow cytometry and real-time quantitative polymerase chain reaction in 36 patients with AS and 30 healthy controls. Demographic features, Ankylosing Spondylitis Disease Activity Score-C-reactive protein (CRP) based, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, HLA-B27, erythrocyte sedimentation rate (ESR), and CRP were evaluated to identify factors associated with BTK expression. Analyses were performed using the Spearman rank correlation test for continuous data, the χ 2 test for categorical data, and that between continuous and dichotomous variables was measured using a point-biserial correlation test. The area under the curve of the receiver operating characteristic curve was used to assess the performance of each candidate biomarker.

Results: BTK gene expression was significantly higher in patients with AS than in controls ( P = 0.026) according to quantitative polymerase chain reaction results. BTK Y223 was also high in CD19 + PBMCs from patients with AS, with CD 19+ BTK Y223+high cells being significantly positively correlated to ESR, CRP, and Ankylosing Spondylitis Disease Activity Score. A negative association was observed between BTK expression and the chest expansion distance. The area under the curve for CD 19+ BTK Y223+ was larger than that for ESR, but CRP still had the largest area.

Conclusions: BTK expression was higher in PBMCs from patients with AS when compared with controls, and was associated with a higher disease activity index, inflammatory reactants, and arthritis and extra-articular manifestations. These findings suggest that BTK expression may play a crucial role in the inflammatory process in individuals with AS.