Department of Medical Biology, Medical University, Plovdiv, Bulgaria; Research Institute at Medical University, Plovdiv, Bulgaria.
Department of Propaedeutics of Internal Diseases, Medical University, Plovdiv, Bulgaria; Clinic of Rheumatology, University Hospital "Kaspela", Plovdiv, Bulgaria.
Int Immunopharmacol. 2024 Nov 15;141:112919. doi: 10.1016/j.intimp.2024.112919. Epub 2024 Aug 14.
Rheumatoid arthritis (RA) is an inflammatory joint disease characterized by persistent synovitis and inflammation. The exact mechanism of mitochondrial function in the presence of inflammation and dysregulation of autophagic processes in the pathogenesis of RA is still unclear. The aim of our study is to determine mitochondrial function, gene and protein levels of biomolecules related to inflammation (YKL-40) and autophagy (LAMPs) and to search a connection between them in the RA context. Twenty newly diagnosed RA patients and ten healthy individuals were included in the study. Disease severity was assessed by ultrasonography. Conventional clinico-laboratory parameters, immunological markers and protein levels of LAMPs and YKL-40 were examined in plasma. Gene expression analysis for the quantitative measurement of LAMPs and YKL-40 were conducted in white blood cells (WBC). A real-time metabolic analysis was performed to assess mitochondrial function and cell metabolism in peripheral blood mononuclear cells (PBMCs). Increase in spare respiratory capacity in PBMCs of RA patients was detected. Decreased LAMPs plasma protein levels and increased protein levels of YKL-40 in RA patients compared to healthy individuals were measured. No significant differences were found in gene expressions. Correlations between mitochondrial, ultrasonographic and protein levels of the biomarkers related with inflammation and autophagy were established. New data on mitochondrial dysfunction in RA patients and links to inflammation and mitophagy are reported. The relationship between dysregulation of mitophagy and joint diseases deserves to be thoroughly investigated as it would be a promising therapeutic approach.
类风湿关节炎（RA）是一种以持续性滑膜炎和炎症为特征的炎性关节疾病。在炎症存在和自噬过程失调的情况下，线粒体功能在 RA 发病机制中的确切机制尚不清楚。我们的研究目的是确定线粒体功能、与炎症（YKL-40）和自噬（LAMPs）相关的生物分子的基因和蛋白水平，并在 RA 背景下寻找它们之间的联系。本研究纳入了 20 名新诊断的 RA 患者和 10 名健康个体。通过超声评估疾病严重程度。检测了血浆中常规临床-实验室参数、免疫标志物以及 LAMPs 和 YKL-40 的蛋白水平。在白细胞（WBC）中进行了 LAMPs 和 YKL-40 的定量测量的基因表达分析。在外周血单核细胞（PBMC）中进行了实时代谢分析，以评估线粒体功能和细胞代谢。检测到 RA 患者 PBMC 中备用呼吸能力增加。与健康个体相比，RA 患者的 LAMPs 血浆蛋白水平降低，YKL-40 蛋白水平升高。基因表达无显著差异。建立了与炎症和自噬相关的生物标志物的线粒体、超声和蛋白水平之间的相关性。报告了 RA 患者中线粒体功能障碍的新数据及其与炎症和线粒体自噬的联系。作为一种有前途的治疗方法，需要深入研究自噬失调与关节疾病之间的关系。
