Dynamics of Adaptive Immune Cell and NK Cell Subsets in Patients With Ankylosing Spondylitis After IL-17A Inhibition by Secukinumab

Abstract

Background: Anti-IL-17A therapy is generally effectively applied in patients with Ankylosing Spondylitis (AS) to achieve and maintain remission. However, the influence of anti-IL-17A on the composition of the immune system is not apparent. Our prospective study was to explore the changes in immune imbalance regarding T cell, B cell and natural killer (NK) cell subsets after secukinumab treatment in AS patients.Methods: Immune cell distribution of 43 AS patients treated with secukinumab for 12 weeks and 47 healthy controls (HC) were evaluated. Flow cytometry using monoclonal antibodies against 25 surface markers was accomplished to explore the frequencies of lineage subsets. The differences between HC, AS pre-treatment, and post-treatment were compared using the paired Wilcoxon test, Mann-Whitney U test, and ANOVA.Results: AS patients had altered immune cell distribution regarding T cell and B cell subsets. Apart from activated differentiation of CD4+ T cell, CD8+ T cell and B cell, higher levels of cytotoxic T (Tc) two cells and Tc17 cells were noted in AS patients. We confirmed that helper T (Th) one cell became decreased; however, Th17 cells and T follicular helper (Tfh) 17 cells went increased in AS. After 12 weeks of secukinumab therapy, CRP and ASDAS became significantly decreased, and meanwhile, the proportions of Th1 cells, Tfh17 cells and classic switched B cells were changed towards those of HC. A decreased CRP was positively correlated with a decrease in the frequency of naïve CD8+ T cells (p = 0.039) and B cells (p = 0.007) after secukinumab treatment. An elevated level of T cells at baseline was detected in patients who had a good response to secukinumab (p = 0.005).Conclusion: Our study confirmed that AS patients had significant multiple immune cell dysregulation. Anti-IL-17A therapy (Secukinumab) could reverse partial immune cell imbalance.

Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients

“…Following the study hypothesis, combined therapy slightly decreased circulating Th1 cells and stabilized Treg cells during the follow-up. In contrast with our findings, Treg cells decreased in skin lesions from patients with psoriasis treated with SCK 41 and decreased peripheral Treg cells in ankylosing spondylitis patients 42 . During IL-17A blockade, peripheral Treg cells remained stable, potentially enhancing the safety of IL-17 inhibition.…”

“…Contrary to our findings, the solitary use of SCK did not show benefit in proteinuria, as per the study and some clinical cases 22 – 24 , 27 . While Treg cell counts were stabilized in our study, a decrease in Treg cell numbers has been observed in cutaneous tissue and at peripheral levels in ankylosing spondylitis 42 . In light of our hypothesis, this could be potentially detrimental if IL-17 is blocked.…”

Identification of symptom clusters in patients with ankylosing spondylitis

“…Previous research has suggested that symptom clusters in cancer may share some mutual biological mechanisms, including pro‐inflammatory cytokines 19 . As an inflammatory disease, AS has elevated levels of pro‐inflammatory cytokines, altered immune cell distribution 20 and also concurs with pain, fatigue, sleep disturbance, and depression 8 . The possible mechanisms of the 4 symptom clusters were discussed based on the literature.…”

Updates on ankylosing spondylitis: pathogenesis and therapeutic agents

“…TNF inhibitors (TNFi) showed good response rates in CD8+NK cell subsets [ 89 ]. However, treatment with secukinumab showed no change in NK cells in patients with AS [ 90 ]. An altered NK cell population could be a cell-based parameter for the selection of therapeutic agents.…”