Rybakov Arseniy V, Yureva Karina A, Khizha Vitaliy V, Kozlova Darya I, Sorokina Lybov S, Zorin Vyacheslav I, Kozhevnikov Aleksei N, Kostik Mikhail M
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences (IEFB RAS), Autoimmune and Autoinflammation Human Diseases Investigation Scientific and Practical Research Group, Saint- Petersburg, 194223, Russian Federation.
Institute of Biomedical Systems and Biotechnology, Peter the Great Saint- Petersburg Polytechnic University, Saint-Petersburg, 195251, Russian Federation.
Curr Rheumatol Rev. 2025;21(3):316-325. doi: 10.2174/0115733971308074240813060452.
Juvenile idiopathic arthritis pathogenesis involves a large number of different immune system cells, which are both sources and targets of chemokines, that affect not only their migration but also survival, proliferation, differentiation, production of all cytokine types, degranulation, and also directly stimulating or suppressing angiogenesis. Studyingthe contribution of chemokines to this disease pathogenesis will make it possible to identify new sensitive and specific markers for its diagnosis and subsequent dynamic monitoring of treatment effectiveness.
The study aimed to identify a list of the most informative diagnostic markers from a wide range of juvenile idiopathic arthritis patients' blood plasma chemokines.
The case-control study included 40 diagnosed pathology patients and 20 healthy agematched children. The content of MCP-1/CCL2, MCP-3/CCL7, MIG/CXCL9, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, IFN-γ, IP-10/CXCL10, and MDC/CCL22 were measured by enzyme- linked immunosorbent assay in blood plasma of each person.
The following chemokines were included in the list of the most promising diagnostic markers: MCP-1, MIP-1α, MIG, RANTES, and IFN-γ. Their blood plasma content in patients with a diagnosed pathology was from 3 to 60 times (MIG) higher than in the conditionally healthy group. Their sensitivity and specificity exceeded 90%.
An increase in their content leads to active monocytes/macrophages migration to the site of inflammation, where they suppress effector T-cell activity by binding suppressor exosomes and activate B-cells by autoantigens presentation received due to joint tissue destruction. This allows us to speak about the predominance of the Th1-mediated immune response during the development of studied disease chronic inflammation.
青少年特发性关节炎的发病机制涉及大量不同的免疫系统细胞,这些细胞既是趋化因子的来源,也是其作用靶点,趋化因子不仅影响细胞的迁移,还影响其存活、增殖、分化、各类细胞因子的产生、脱颗粒,并且直接刺激或抑制血管生成。研究趋化因子对该疾病发病机制的作用,将有助于识别新的敏感且特异的诊断标志物,用于疾病诊断及后续治疗效果的动态监测。
本研究旨在从大量青少年特发性关节炎患者血浆趋化因子中确定一系列最具诊断价值的标志物。
病例对照研究纳入了40例确诊病例和20例年龄匹配的健康儿童。采用酶联免疫吸附测定法检测每个人血浆中MCP-1/CCL2、MCP-3/CCL7、MIG/CXCL9、MIP-1α/CCL3、MIP-1β/CCL4、RANTES/CCL5、IFN-γ、IP-10/CXCL10和MDC/CCL22的含量。
最具诊断潜力的标志物包括:MCP-1、MIP-1α、MIG、RANTES和IFN-γ。确诊患者血浆中这些趋化因子的含量比健康对照组高3至60倍(MIG)。其敏感性和特异性均超过90%。
这些趋化因子含量的增加会导致活性单核细胞/巨噬细胞迁移至炎症部位,在那里它们通过结合抑制性外泌体抑制效应T细胞活性,并通过关节组织破坏产生的自身抗原呈递激活B细胞。这使我们可以认为在所研究疾病的慢性炎症发展过程中,Th1介导的免疫反应占主导地位。