Study on the late stage of autophagy in primary gouty arthritis / 中华风湿病学杂志

ABSTRACT

Objective:To explore the expression and clinical significance of late autophagy in per-ipheral blood mononuclear cells (PBMCs) of patients with primary gouty arthritis (GA).Methods:Peripheral blood, clinical data, and laboratory tests were collected from 30 patients with acute gout (AG), 30 patients with intermittent gout (IG), and 50 healthy controls (HC). Quantitative polymerase chain reaction (RT-qPCR) was used to detect mRNA expression levels of autophagy-related genes (ATG5, ATG12, ATG16, ATG3, ATG7, ATG10, ATG4B, LC3-2/LC3B). Measurement data conformed to normal distribution were tested using t test or analysis of variance (ANOVA), and non-normal distribution data were tested using Mann-Whitney test or Kruskal-Wallis H test. SNK was used for pairwise comparison among the three groups. Correlation between variables was tested by Spearman correlation analysis. Results:① The expression level of ATG5 mRNA,ATG12 mRNA, ATG16 mRNA, ATG10 mRNA and LC3-2 mRNA in the AG group was lower than that of the IG group and the HC group, and the expression level of the IG group was lower than that of the HC group[9.16×10 -3(6.04×10 -3, 15.00×10 -3) vs 14.48×10 -3(9.95×10 -3, 21.38×10 -3) vs 0.08×10 -3(12.21×10 -3, 42.79×10 -3), H=19.377, P<0.001; 18.89×10 -3(13.85×10 -3, 24.92×10 -3) vs 21.13×10 -3(12.11×10 -3, 28.06×10 -3) vs 33.57×10 -3(13.11×10 -3, 49.89×10 -3), H=7.545, P=0.023; 8.72×10 -3(4.96×10 -3, 13.74×10 -3) vs 10.62×10 -3(7.48×10 -3, 24.71×10 -3) vs 20.07×10 -3(11.99×10 -3, 39.56×10 -3), H=20.962, P<0.001; 1.05×10 -3(0.73×10 -3, 1.84×10 -3) vs 1.60×10 -3(0.93×10 -3, 2.58×10 -3) vs 1.69×10 -3(1.05×10 -3, 3.54×10 -3), H=8.193, P=0.017; 2.31×10 -3(1.22×10 -3, 3.53×10 -3) vs 2.78×10 -3(1.68×10 -3, 5.96×10 -3) vs 3.68×10 -3(2.00×10 -3, 5.67×10 -3) , H=7.135, P=0.028]. The expression level of ATG4B mRNA in the AG and IG group was higher than that in HC group, and there was significant difference between IG group and AG group, IG group and HC group[9.95×10 -3(6.32×10 -3, 12.23×10 -3) vs 10.86×10 -3 (8.80×10 -3, 17.03×10 -3) vs 8.07×10 -3(5.52×10 -3, 11.63×10 -3), H=8.531, P=0.014]. There was no significant difference between the ATG3 mRNA and ATG7 mRNA groups ( H=0.539, 3.739, bothall P values >0.05). ② The results of Spearman correlation analysis suggested that in patients with acute gout, ATG3 was negatively correlated with PDW and MPV ( r=-0.499, P=0.006; r=-0.463, P=0.011); ATG4B was positively correlated with HDL-C ( r=0.408, P=0.048); ATG7 was negatively correlated with GLOB ( r=-0.554, P=0.001); ATG10 was positively correlated with ALB ( r=0.412, P=0.024) and negatively correlated with Crea and hsCRP ( r=-0.459, P=0.011; r=-0.375, P=0.045); ATG12 was negatively correlated with MO ( r=-0.434, P=0.017); ATG16 was negatively correlated with ALT and AST ( r=-0.389, P=0.034; r=-0.366, P=0.047); LC3-2 was positively correlated with UA ( r=0.381, P=0.041) and negatively correlated with MPV and PDW ( r=-0.413, P=0.026; r=-0.449, P=0.015). In patients with intermittent gout, ATG3 and ATG4B were negatively correlated with apoB100 ( r=-0.555, P=0.011; r=-0.462, P=0.040); ATG5 was negatively correlated with Crea ( r=-0.456, P=0.011); ATG10 was negatively correlated with TC, LDL-C, and apoB100 ( r=-0.526, P=0.017; r=-0.556, P=0.011; r=-0.515, P=0.020). Conclusion:Autophagy is involved in the development of gout, and is correlated with ibflammatory and metabolic indicators, suggesting that autophagy is an important feature in the pathogenesis of GA.