Comprehensive Phenotyping of Circulating T- and B-Cell Subsets in Patients with Ankylosing Spondylitis Associated with Crohn’s Disease

Abstract

Highlights What are the main findings? Patients with ankylosing spondylitis associated with Crohn’s disease exhibit decreased effector memory Th and Tcyt cell subsets compared to patients with Crohn’s disease, as well as an increase in T-regulatory cells (Tregs) in the peripheral blood compared with other groups. Phenotypic alterations in the CD39/CD73 profile of Tregs were also observed. Patients with ankylosing spondylitis associated with Crohn’s disease exhibit decreased Tfh17 levels compared to patients with ankylosing spondylitis alone, and a decrease in ‘switched’ memory B cells compared to patients with Crohn’s disease alone. Both of these populations were negatively correlated with acute-phase markers. What are the implications of the main findings? The observed phenotypic alterations in T cell-mediated adaptive immunity may reflect a predominantly pro-inflammatory profile, with possible signs of diminished regulatory activity. The changes noted in the humoral component of the adaptive immune response in this condition might be compensatory in nature and could potentially be associated with resolution of inflammation. However, further functional studies are needed to confirm this hypothesis. Abstract Background: Ankylosing spondylitis (AS) associated with Crohn’s disease (CD) is a nosological form of spondyloarthropathies with a low population prevalence. The pathogenesis of this disease is not fully understood, and there are no precise differential diagnostic methods to distinguish AS associated with CD from AS and CD separately in the early stages of the disease. The main objective for this study is to define lymphocyte-mediated immunity in patients with AS associated with CD. Methods: For the pilot study, we recruited four groups: CD (n = 16), AS+CD (n = 13), AS (n = 13) and healthy controls (HC, n = 26). Immune phenotyping of peripheral blood lymphocytes was carried out via flow cytometry. Results: In the AS+CD group, circulating regulatory T-cell (Treg) levels were increased compared to the other groups. The frequency of CD73+ Tregs within the effector memory (EM) compartment was also elevated in the AS+CD group relative to the AS and CD groups alone. At the same time, the EM Tcyt and EM Th populations were lower in the AS+CD group compared to the CD group. Tfh17 levels were lower in the AS+CD group than in the AS group and showed a positive correlation with Bm5 and ‘switched’ memory B cells. Additionally, Tfh17 and ‘switched’ memory B cells correlated negatively with acute-phase markers, whereas Tfh2 correlated positively with the BASDAI activity index. Conclusions: In patients with AS associated with CD, exhaustion of the regulatory compartment of adaptive immunity is seen, whereas the humoral component appears oriented towards resolving the inflammatory responses.