Clonorchis sinensis-Derived Protein Attenuates Inflammation and New Bone Formation in Ankylosing Spondylitis

Abstract

Helminth infections and their components have been shown to have the potential to modulate and attenuate immune responses. The objective of this study was to evaluate the potential protective effects of Clonorchis sinensis-derived protein (CSp) on ankylosing spondylitis (AS). Cytotoxicity of CSp at different doses was assessed by MTS and flow cytometry before performing experiments. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analyzed using flow cytometry. The levels of INF-γ, IL-17A, TNF-α, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). SKG mice were treated with CSp or vehicles. Inflammation and new bone formation were evaluated using immunohistochemistry, positron emission tomography (PET), and micro-computed tomography (CT). Treatment with CSp resulted in no reduced cell viability of PBMCs or SFMCs until 24 h. In experiments culturing PBMCs and SFMCs, the frequencies of IFN-γ and IL-17A producing cells were significantly reduced after CSp treatment. In the SKG mouse model, CSp treatment significantly suppressed arthritis, enthesitis, and enteritis. Micro-CT analysis of hind paw revealed reduced new bone formation in CSp-treated mice than in vehicle-treated mice. We provide the first evidence demonstrating that CSp can ameliorate clinical signs and cytokine derangements in AS. In addition, such CSp treatment could reduce the new bone formation of AS.

A protein extracted from Metagonimus yokogawai alleviates inflammation in patients with Ankylosing Spondylitis

“…To the best of our knowledge, this study is the rst to demonstrate the bene cial effect of M. yokogawairelated molecules on the symptoms and cytokine imbalances in AS. Previous research showed that CSp treatment could reduce the severity of AS symptoms through the systemic and local suppression of proin ammatory mediators [12]. In this study, we aimed to nd an alternative therapeutic target for AS.…”

“…However, using helminth products as therapeutic agents has advantages over a live infection. Lee et al previously clari ed the therapeutic effect of Clonorchis sinensis-derived protein (CSp) against AS using a murine model [12]. Any trematodes-induced proteins might be active, similar with the basis of the bene cial effect of CSp in the pathogenesis, however, it is still lacking to be known.…”

Ankylosing spondylitis coexisting with Clonorchis sinensis infection: A case report

“…Earlier research indicated that C. sinensis might worsen arthritis progression, with this adverse effect potentially linked to changes in immune cell profiles and associated cytokine levels[ 17 ]. However, another study suggested that C. sinensis -induced protein could suppress new bone formation in a mouse model in vivo [ 18 ]. Notably, the role of C. sinensis infections in modulating arthritis symptoms is a multifaceted and complex phenomenon.…”

Clonorchis sinensis infection modulates key cytokines for essential immune response impacted by sex

“…It is interesting to establish a long-standing, persistent infection model (e.g., more than 24 weeks) to track the dynamic changes of cytokines and investigate the intrinsic mechanism. Helminth infections and their components have been shown to have the potential to modulate and attenuate immune responses [25]. C. sinensis infection is carcinogenic to human [26][27][28].…”