Effect Of Tumor Necrosis Factor Inhibitor On Autophagy In Patients With Rheumatoid Arthritis

Objectives:The expression of autophagy-related genes in peripheral blood mononuclear cells(PBMCs)of patients with rheumatoid arthritis(RA)was detected,and the changes of autophagy-related genes before and after treatment with tumor necrosis factor inhibitors(TNFi)were observed.To explore whether autophagy is involved in the pathogenesis of RA,the relationship between autophagy-related genes and RA,and the effect of TNFi treatment on the autophagy level of patients with RA.Methods:(1)Collect 50 RA patients(RA group)and 50 healthy controls(HC group)clinical,laboratory data and peripheral blood samples,extract peripheral blood mononuclear cells(PBMCs)from patients,and use real-time quantitative polymerase chain reaction technology to detect the expression levels of ULK1,ATG13,ATG17,LC3 and P62 in PBMCs,and conducts correlation analysis with clinical indicators.(2)25 patients with moderate to severe disease activity were selected and treated with TNFi for 3 months.Clinical and laboratory indicators and peripheral blood samples were collected before and after treatment,using PCR to detect the expression levels of ULK1,ATG13,ATG17,LC3 and P62 in PBMCs.The disease activity and autophagy-related genes were compared before and after treatment.Result: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).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).The correlation analysis suggested that ATG17 was positively correlated with tender joint count(TJC),swollen joint count(SJC),health assessment questionnaire(HAQ)and disease activity score in 28 joints(DAS-28)(P<0.05),the area under the ROC curve was 0.839,and the sensitivity and specificity were 0.74 and 0.86.2.The TNFi combined with 2 conventional synthetic disease-modifying antirheumatic drugs(csDMARDs)in RA patients achieved higher 70%remission(ACR70)than the combined use of 1 csDMARD(P<0.05).There was no significant difference in liver and kidney function damage,the disease activity,the levels of ATGs between the two groups(P>0.05).The ATG17 and LC3 in RA patients whose disease activity reached remission was significantly lower(P<0.05).3.Compared with before treatment with TNFi,ATG17,TJC,SJC,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).Conclusion:(1)The abnormal expression of autophagy-related genes ULK1,ATG17,LC3 and P62 in PBMCs of patients with RA suggests that autophagy is involved in the pathogenesis of RA.ATG17 is obviously positively correlated with disease activity,and it is expected to be a marker for evaluating RA disease activity and diagnosis.(2)After TNFi treatment,disease activity indicators and inflammation indicators of RA patients improved significantly,suggesting that TNFi can effectively inhibit the inflammation of RA.After TNFi treatment,ATG17 was significantly reduced,and RA patients whose disease activity was relieved after treatment had significantly lower LC3 and ATG17,suggesting TNFi may play its role by influencing the level of autophagy in patients with RA,and autophagy may be a new target for the treatment of RA.