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Background and aims 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 pulse 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 increased autophagy in LN kidney. 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 CR(p=0.025) (Table 1). 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). Conclusions Low renal p62 expression was associated with less severe 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.

Background and Aims Iguratimod (IGT) is a small molecular immunomodulatory drug and has been approved for treating rheumatoid arthritis. In our previous work, IGT ameliorates lupus-like disease in MRL/ lpr mice by inhibiting abnormal B cell differentiation. The aim of this study is to further investigate the effects of IGT on human B cells. Methods We established a set of stimulations to induce naive human B cell into plasmablast (PB) in vivo . We also enrolled 7 patients with refractory lupus nephritis (LN) to assess the potential efficacy of IGT. Results IGT significantly attenuates the generation of CD19+CD20-CD27hiCD38hi plasma cells upon both BCR-dependent and independent stimulations. IGT affects neither proliferation or apoptosis of B cell in vitro . In further investigation on B cell differentiation signalling pathwasys, we identifies that Blimp-1 and Xbp-1 can be remarkably impaired by IGT both in transcriptional and protein level; while Jak/STAT or NF-κB signalling are intact with IGT treatment. For explosive clinical study, seven patients with refractory LN were enrolled and administrated with IGT and steroids. ALL of these patients surprisingly show improved proteinuria after 8 week treatment. One patient quit the treatment because of anaemia. Conclusions IGT has a unique effect to arrest B cell terminal differentiation, which provides strong evidence that this drug could be a new candidate drug to treat B cell related autoimmune diseases such as lupus.