#317 Autophagy related Protein 5 is a promising autophagy marker in lupus nephritis with good predictive value of response to treatment

Abstract Background and Aims Conventional biomarkers may not be useful enough to monitor response to treatment in lupus nephritis (LN). Increasing evidence implicates autophagy in the pathogenesis of LN. This study assessed serum autophagy related protein 5 (ATG5) and its staining in renal biopsies in LN and its relation to the diagnosis of autophagy and treatment response. Method A pilot, prospective study included 31 active LN patients and 9 healthy subjects. ATG5 was assessed in LN renal biopsies before starting treatment and in the serum of all subjects. Serum ATG5 was followed at 3 and 6 months after treatment. Results Serum ATG5 was significantly low in LN at cut-off ≤312.3 ng/l with AUC 0.943. The prevalence of ATG5 staining in renal biopsies with summation score >3 was 87.1% (27 patients) and multiplication score >8 was 58.1% (18 patients). There was a significant recovery of serum autophagy marker ATG5 in response to treatment (baseline versus 3 and 6 months after treatment) p-value <0.001. Complete and partial responders had lower summation and multiplication scores in biopsies also, they showed better recovery of serum ATG5 at 3 and 6 months versus non-responder p-values of 0.004, and 0.009 <0.001, 0.001 respectively. Summation score of ATG5 ≤6 in biopsies can predict response to treatment by AUC 0.88, sensitivity 69.57%, specificity 100%, PPV 100%, and NPV 53.3%. Patients who received MMF had better responses than Cyclophosphamide (P-value 0.042). Serum ATG5 at 3 and 6 months was negatively correlated with serum creatinine and protein/creatinine ratio while positively correlated with e-GFR (p-value <0.05). ATG5 Summation and multiplication scores were negatively correlated with serum ATG5 after 6 months (p-value 0.026, 0.018). Conclusion ATG5 is a promising autophagy marker in LN with good predictive value for treatment response. A lower autophagy biopsy score is linked to a positive response to treatment especially with MMF.