Background:Autophagy is a phenomenon of “self-phagocytosis” in eukaryotic cells, which maintains cell homeostasis by transporting intracellular materials to lysosomes for degradation and recycling. In recent years, studies have shown that autophagy may be involved in the pathogenesis of rheumatoid arthritis(RA)[1], but its specific mechanism is still unclear.Objectives:The expression levels of autophagy-related genes(ATG) unc-51-like kinase 1(ULK1), ATG13, ATG17, microtubule associated protein 1 light chain 3 (LC3), and P62 in peripheral blood mononuclear cells (PBMC) of patients with RA were detected, and their role and clinical significance in the pathogenesis of RA were explored.Methods:Real-time fluorescent quantitative PCR was performed to detect the expression levels of ULK1, ATG13, ATG17, LC3, and P62 in PBMCs of 50 RA patients, 50 healthy controls (HC), and 25 moderate to severe RA patients before and after treatment. Then, t test, χ2 test, Mann-Whitney U test, Pearson test were used for statistical analysis.Results:1.The levels of hsCRP, white blood cell(WBC), neutrophils(GR), platelet(PLT) and plateletcrit(PCT) in RA group were higher than those in HC group (P <0.05). Lymphocytes (LY), red blood cell(RBC), hemoglobin(HGB), hematocrit(HCT), mean corpuscular hemoglobin(MCH), mean red blood cell volume(MCV) and mean red blood cell hemoglobin concentration(MCHC) in RA group were lower than those in HC group (P <0.05). 2.The expressions of ULK1, ATG17, and LC3 in RA group were higher than those in HC group, while the expressions of P62 was lower than those in HC group(P<0.05) (Figure 1). The correlation analysis suggested that ATG17 was positively correlated with tender joint count (TJC), swollen joint count (SJC), and health assessment questionnaire (HAQ) (P<0.05); ULK1 and HAQ were negatively correlated (P<0.05).3. Compared with before treatment with TNFi, ATG17, HAQ, DAS-28, ESR, hsCRP, WBC, GR, PLT and PCT were significantly reduced after treatment (P<0.05); the expressions of RBC, HCT, MCV and MCH were significantly increased after treatment,(P<0.05); ULK1, ATG13, LC3, P62 and other related clinical and laboratory indicators were not significantly different before and after treatment with TNFi (P>0.05).Figure 1.The expression levels of ATGs in HC and RA groups.Conclusion:There is abnormal expression of autophagy genes in the peripheral blood of RA patients. ULK1, ATG17, LC3 and P62 may be related to the pathogenesis of RA, among them, ATG17 may regulate the pathogenesis of RA by participating in the TNF-α pathway.References:[1]Rockel Jason S,Kapoor Mohit,Autophagy: controlling cell fate in rheumatic diseases.[J].Nat Rev Rheumatol, 2016, 12: 517-31.Disclosure of Interests:Yu-Feng Qing Grant/research support from: Science and Technology Project of Nanchong City (no.18SXHZ0522), Fei Dai: None declared, Quan-Bo Zhang Grant/research support from: the National Natural Science Foundation of China(General Program) (no.81974250), and Science and Technology Plan Project of Sichuan Province (no.2018JY0257), Yi-Ping Tang: None declared, Zeng-Rong Dong: None declared, Yi-Xi He: None declared, Yi Jiang: None declared, Yu-Qin Huang: None declared, Jianxiong Zheng: None declared
Red Blood Cell Supernatant Potentiates LPS-Induced Proinflammatory Cytokine Response From Peripheral Blood Mononuclear Cells
