Abstract

Existing biomarkers are often insufficient for adequately tracking treatment outcomes in lupus nephritis (LN). Growing evidence points to a significant role of autophagy in LN pathogenesis. This study aimed to evaluate circulating levels of autophagy-related protein 5 (ATG5) alongside its immunohistochemical expression in kidney biopsy from LN patients, and to examine its utility as a diagnostic indicator and predictor of therapeutic response. This pilot prospective research enrolled 31 patients with active LN and 9 age and sex matched normal controls. Immunohistochemical evaluation of ATG5 expression was conducted on renal biopsy specimens collected before the commencement of medication, while blood ATG5 levels were evaluated in all subjects. Serial serum ATG5 evaluations were performed at 3-month and 6-month intervals after the initiation of therapy. Circulating ATG5 levels were significantly decreased in LN patients relative to controls (cut-off ≤312.3 ng/l; AUC=0.943; sensitivity 100%; specificity 88.9%). Renal tissue ATG5 expression was detected in 96.7% of patients; strong expression identified in 87.1% using summation scoring (score >3) and in 58.1% using multiplication scoring (score >8). A biopsy summation score ≤6 predicted treatment response with AUC of 0.88, sensitivity 69.57% and 100% specificity. Treatment was associated with significant ATG5 recovery over 6 months (p<0.001), with responders demonstrating lower biopsy scores and greater serum ATG5 improvement versus non-responders (p=0.004, p=0.009, respectively). Mycophenolate mofetil (MMF) treatment yielded superior outcomes compared to cyclophosphamide (p=0.042). The summation and multiplication scores of ATG5 exhibited a negative correlation with serum ATG5 after six months (p <0.026 and p<0.018, respectively). In conclusion, ATG5 represents a valuable autophagy-related biomarker in LN, offering reliable predictive utility for treatment outcomes. Lower intra-renal ATG5 expression scores are associated with favourable therapeutic responses, particularly in patients receiving MMF.

Keywords: Autophagy; ATG5; Lupus nephritis, eGFR.

Date received: 29 April 2026; accepted: 30 July 2026

PMID:
0000000