276\u2005Baseline renal autophagy-related protein p62 expression level predicts 24-week treatment effectiveness in lupus nephritis

Abstract

Background Previous studies found autophagy contributes to the pathogenesis of systemic lupus erythematosus (SLE). Whether autophagy is involved in lupus nephritis (LN) is not elucidated. P62 is a specific substrate that is degraded through autophagy-lysosomal pathway. Methods Immunohistochemistry staining was performed to evaluate expressions of p62 in the biopsy kidney tissue of LN patients (n=128) and normal control (n=6). One hundred and five patients were given prednisone +CTX\u2009pulse therapy as induction treatment and followed by 24 weeks. Clinicopathologic features and induction phase remission efficacy were recorded and correlated with renal p62 expression level. Results Compared with the controls, the expression of p62 was significantly decreased in LN biopsy tissues (p=0.0013), suggesting increasing autophagy in LN kidney. However, patients with low expression of p62 had less severe nephritis, showing significantly less proteinuria, fewer interstitial fibrosis score and higher estimated creatinine clearance rates (p=0.0122, p=0.0048, p=0.0231, respectively). Logistic regression analysis revealed that lower renal p62 expression was an independent factor associated with achieving complete remission (CR) in 24 weeks (p=0.025). Patients with low p62 were more likely and quicker to achieve CR (Person Chi-Square test, p=0.001; Kaplan-Meier test, p=0.0294).Abstract 276 Table 1 Univariate regression analysis for outcome of LN patients treated with prednisone+ pulse CTX therapy Conclusions Low renal p62 expression was associated with less severe lupus nephritis and better short-time outcome. Because low p62 expression is the result of high level of autophagy, this data suggested that autophagy might play a protective role in LN kidney. More studies are needed to evaluate the role autophagy plays in multiple organs and cell subtypes in SLE. Funding Source(s): None