Expression And Clinical Significance Of Autophagy-related Genes In Patients With Rheumatoid Arthritis

Objective:1.Investigate the expression of autophagy-related genes in peripheral blood of patients with RA and explore its relationship with clinical indicators.2.Compared the changes of clinical indicators and autophagy-related genes in patients before and after treatment with TNF-α inhibitors to analyze the effect of TNF-α inhibitors on autophagy-related genes in RA patients.Method:1.Collected peripheral blood samples from 59 patients with rheumatoid arthritis(RA group)and 55 healthy controls(HC group),extract RNA and protein from peripheral blood mononuclear cells(PBMCs).Real-time fluorescent quantitative PCR and Western Blot technology were used to investigate the expression of autophagy-related genes(Atg)3,Atg5,Atg12,Atg16,Beclin-1,LC-3B in two groups.Analyzed the correlation with clinical indicators.2.The clinical data and peripheral blood samples of 15 patients with newly diagnosed RA who were in the middle and severe active phase without formal treatment were collected before and after treatment.Compared their clinical indicators and the above-mentioned genetics before and after treatment.Result:1.The granulocyte,erythrocyte sedimentation rate,and high-sensitivity C-reactive protein in the RA group were significantly higher than those in the HC group(P<0.05).2.Detecting the mRNA expression levels of autophagy-related genes in two groups,it was found that the expression of Atg3,Atg12,and LC-3 in RA group were higher than those in HC group(P<0.05);Atg16L1 expression was lower than that in HC group(P<0.05);There was no difference in the mRNA expression levels of Beclin-1 and Atg5 in the group(P>0.05).3.Correlation analysis showed that the Atg3 expression level in the RA group has negative correlation with white blood cells,granulocyte,the number tender joints of 28 counted,and disease activity score in 28 joints(DAS28),(P<0.05);Atg12 expression level was negatively correlated with white blood cells and granulocyte;Beclin-1 expression level was negatively correlated with white blood cells,granulocyte,monocytes;LC-3 expression level was positively correlated with erythrocyte sedimentation rate,the number swollen joints of 28 counted(SJC)(P<0.05);no correlation was found between Atg5,Atg 16 with clinical indicators(P>0.05).No correlation was found between the aforementioned autophagy-related genes and clinical indicators in the HC group(P>0.05).4.Detecting the protein expression of autophagy-related genes in the two groups,it was found that the protein expression of Atg16L1,and LC-3B in RA group was higher than those in HC group(P<0.05),and there was no significant difference in Atg3,Atg5,Atg12,Beclin-1 expression(P>0.05).5.In the RA group,white blood cells,granulocyte,erythrocyte sedimentation rate,high-sensitivity C-reactive protein,TJC,SJC,and DAS28 were significantly reduced after treatment with TNF-α inhibitors(P<0.05),and there was no significant change in lymphocyte and monocyte(P>0.05).6.In the RA group,before and after treatment with TNF-α inhibitors,the expression of Atg3,Atg12,and LC3 mRNA were reduced(P<0.05),the expression of Atg 16 mRNAwere increased(P<0.05),the expression of Atg5 and Beclin-1 haved not significant difference(P>0.05).7.In the RA group,before and after treatment with TNF-α inhibitors,the expression of Atg16L1,LC3B protein were significantly reduced(P<0.05),and Atg3,Atg5,Atg12,and Beclin-1 haved not significantly difference(P>0.05).Conclusion:1.There are abnormalities of autophagy-related genes in RA patients.It is speculated that autophagy may play a role in the pathogenesis of rheumatoid arthritis;autophagy-related genes are related to some clinical indicators.It is speculated that autophagy may be closely related to the condition of RA patients.2.After using the TNF-α inhibitor,the inflammation index and DAS28 of the patients were significantly reduced,sugged that the TNF-α inhibitor can significantly improve the condition of RA patients and reduce the disease activity of patients.3.After using TNF-α inhibitors,autophagy-related genes of patients with RA have changed.It is speculated that TNF-α inhibitors may improve the patient’s condition by changing the autophagy level of RA patients.