Dynamics of T-cell receptor repertoire in patients with ankylosing spondylitis after biologic therapy

Abstract

Introduction: Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease in which T-cell immune responses play important roles. AS has been characterized by altered T-cell receptor (TCR) repertoire profiles, which are thought to be caused by expansion of disease-related TCR clonotypes. However, how biological agents affect the TCR repertoire status and whether their therapeutic outcomes are associated with certain features or dynamic patterns of the TCR repertoire are still elusive.

Material and methods: We collected clinical samples from AS patients pre- and post-treatment with biologics. TCR repertoire sequencing was conducted to investigate associations of TCRα and TCRβ repertoire characteristics with disease activity and inflammatory indicators/cytokines.

Results: Our results showed that good responders were associated with an increase in the TCR repertoire diversity with higher proportions of contracted TCR clonotypes. Additionally, we further identified a positive correlation between TCR repertoire diversity and interleukin (IL)-23 levels in AS patients. A network analysis revealed that contracted AS-associated TCR clonotypes with the same complementary-determining region 3 (CDR3) motifs, which represented high probabilities of sharing TCR specificities to AS-related antigens, were dominant in good responders of AS after treatment with biologic therapies.

Conclusions: Our findings suggested an important connection between TCR repertoire changes and therapeutic outcomes in biologic-treated AS patients. The status and dynamics of TCR repertoire profiles are useful for assessing the prognosis of biologic treatments in AS patients.

Keywords: Ankylosing spondylitis; Biologics; T-cell receptor (TCR); TCR repertoire; TCR sequencing.