The Role Of Chaperone-mediated Autophagy In Systemic Lupus Erythematosus

Objective:To detect the expression of chaperone-mediated autophagy(CMA)marker lysosome-associated membrane proteins(LAMP)-2 in peripheral blood mononuclear cells(PBMCs)from patients with systemic lupus erythematosus(SLE)and to explore the relationship between the expression and the pathogenesis of SLE.Method:1.The mRNA expression of LAMP-2 in PBMCs isolated from 88 SLE patients(SLE)and 40 healthy persons(control group)were detected by real-time quantitative PCR,and the correlation between clinical characteristics and disease activity was analyzed.2.Western Blot(WB)was used to detect the expression of LAMP-2A protein in PBMCs obtained from the two groups.3.Laser scanning Confocal Microscopy(LSCM)examination was used to detect the co-localization of LAMP-2A and lysosome in PBMCs.Result:1.The expression level of LAMP-2 was 1.015±0.667 in the normal control group and 2.402±2.233 in the SLE group(p=0.000).Further analysis showed that LAMP-2 expression level was positively correlated with SLEDAI(r = 0.312,P = 0.003),and the incidence of renal damage in patients with increased LAMP-2 expression was significantly higher than that in the unelevated patients(40.7% vs 16.3%,P = 0.013).There are not significant difference in other clinical and laboratory indicators,as well as the use of hormones、hydroxychloroquine and immunosuppressive agents.2.The expression level of LAMP-2A protein in in PBMCs from SLE patients was significantly higher than that in PBMCs from control group(0.482±0.207 and 0.294 ±0.190,t=2.319,p=0.03).3.The fluorescence intensity of both LAMP-2A and lysosome in PBMCs from SLE patients was higher than that in PBMCs from normal control group.Conclusion:The findings of increased expression of LAMP-2 mRNA,LAMP-2A protein and co-localization of LAMP-2A and lysosome in SLE patients suggest that the function of CMA in SLE patients is enhanced,and its correlation with SLE disease activity and the development of renal involvement indicates that CMA might play a role in the pathogenesis SLE.