Autophagy Related Proteins Expressions And Their Associations With Clinicopathologic Features Of Lupus Nephritis

Background:Systemic lupus erythematosus(SLE)is a complex and heterogeneous autoimmune disease of unknown cause that can affect virtually every organ.Many studies have suggested genetic,hormonal,immunologic,and environmental factors were involved in the pathogenesis of SLE,but it has not been elucidated completely.Lupus nephritis(LN)is one of the most common and severe complications in SLE patients,the current treatments rely mainly on glucocorticoids and immunosuppressants,which are not effective for everyone and have considerable adverse effects when used for a long time.Therefore,studies on pathogenesis of LN has always been demanded.Autophagy is a lysosome-based process through which cytoplasmic constituents can be degraded.With the rapid progress over the past ten years,autophagy has been currently one of the hottest fields in life science.Previous studies has found that autophagy can affect almost all parts of the immune system and play an important role in the pathogenesis of autoimmune diseases.Growing lines of evidence has also revealed the relationship between autophagy and SLE regarding genetic analysis,immune cell biology.However,as to the autophagy level in kidney tissue of LN and how autophagy is involved in clinical research,no publication is available.The aim of our study is to identify the local expressions of autophagy-related proteins in the kidney tissue of LN patients,and to evaluate their possible implications in the clinicopathologic features and outcomes of the disease.Materials and Methods:1).128 cases of renal tissue samples from patients with LN were collected between December 2009 and April 2015 in Department of Rheumatology,Renji Hospital.We used the autophagosome marker,LC3B,and autophagy flux marker,p62/SQSTM1(p62),by using immunohistochemistry to evaluate autophagy in LN and paracancerous normal renal tissue.Electron microscopy as well as immunofluorescence with confocal microscopy were used to confirm the presence of autophagic vacuoles.Analysis was done concerning the correlation between autophagy related protein and clinical pathological characteristics;2).95 individuals in the whole study population were given cyclophosphamide(CTX,0.5-1g/m~2for at least 6 times)as the induction treatment and followed for 6 months,the univariate and multivariate logistic regression analysis were performed to assess the effect of autophagy related protein on the induction efficacy and other risk factors independently associated with the remission rates.Results:Immunohistochemical analyses on renal biopsies showed LC3 proteins were expressed at both the tubule-interstitial and glomerular level,and the glomerulus LC3 IOD score was positively correlated with quantitation of 24-hour proteinuria,while LC3 staining did not differ between patients with LN and normal control.P62 protein was only expressed in tubule-interstitial levels,and was lower in LN patients than in normal control(p=0.0013).Compared to LN patients with high tubular anti-p62 expressions,those with low expressions were more likely to have complete remission at the time of 6 months,higher estimated creatinine clearance rates(p=0.0036)and interstitial fibrosis scores(p=0.007).High levels of p62 and non-use of antimalarial drugs were both independently risk factors for the rate of short-time remission of LN patients.Conclusions:Our data shows the correlation between autophagy-related proteins and clinicopathologic features and outcomes of LN,providing evidence for a role of autophagy in the pathogenesis and development of LN,and a possibility for the prediction of short-time outcomes by p62.