Altered expression of the spliceosome components in leukocytes subsets from patients with ankylosing spondylitis: association to disease pathogenesis and therapeutic response

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory disease whose etiopathogenesis remains incompletely understood. Splicing, a posttranscriptional process essential for RNA maturation, has recently been implicated in several human diseases through pathological deregulation of the spliceosome; however, alterations of the spliceosome and their modulation by therapeutic responses have not yet been described in AS. The objectives of this study were: (1) to evaluate the potential deregulation of the spliceosome in leukocytes from AS patients and its involvement in disease pathophysiology, and (2) to analyze the in vivo effects of anti-TNF drugs on spliceosome components in these cells. A cross-sectional study was conducted with 32 AS patients and 29 healthy donors (HDs), and a three-month longitudinal study was performed in eight AS patients undergoing anti-TNFα therapy. Disease activity was assessed using the BASDAI index, along with CRP and ESR levels; physical function was measured by BASFI, spinal mobility by BASMI, and structural damage by mSASSS. The expression of selected components of the major (n=12) and minor (n=4) spliceosomes, as well as splicing factors (n=28), was evaluated in purified leukocytes using Fluidigm technology, while inflammatory marker expression was assessed in parallel by RT-PCR.