Exploring potential multiple molecular biomarkers that predict treatment response in patients with lupus nephritis

Abstract

Limited knowledge exists regarding biomarkers that predict treatment response in Lupus nephritis (LN). We aimed to identify potential molecular biomarkers to predict treatment response in patients with LN. We enrolled 66 patients with active LN who underwent renal biopsy upon enrollment. Serum and urine samples were collected longitudinally, and we measured 12 biomarkers in each sample using a multiplex immunofluorescence assay. These biomarkers included monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein 10 (IP-10), interferon-γ (IFN-γ), interleukin 6 (IL-6), interleukin 16 (IL-16), interleukin 17 (IL-17), interleukin 23 (IL-23), tumor necrosis factor receptor II (TNF-RII), vascular cell adhesion molecule 1 (VCAM-1), retinol-binding protein 4 (RBP 4), vitamin D binding protein (VDBP), and neutrophil gelatinase-associated lipocalin (NGAL). Patients were categorized into two groups based on their 1-year treatment response to Mycophenolate mofetil (MMF)-based therapy: 50 responders and 16 non-responders. Only urine IL-17 (uIL-17) showed baseline level differences between the two groups, with higher in responders. In ROC curve analyses assessing the predictive performance of biomarkers, baseline uIL-17 and changes in uIL-6 and uIL-23 levels at 3 months could predict the 1-year treatment response, showing AUC values of 0.70 (95% CI 0.54-0.87), 0.70 (0.54-0.86), and 0.71 (0.57-0.85), respectively. Combining uIL-6 and uIL-23 into a model improved predictability, achieving an AUC of 0.75 (0.61-0.90). Baseline uIL-17 levels and early changes in uIL-6 and uIL-23 could serve as potential biomarkers to predict 1-year treatment response in lupus nephritis patients receiving MMF-based therapy.

Keywords: Biomarker; Lupus nephritis; Treatment response.

Fig. 1

Longitudinal patterns of six biomarkers between responders and non-responders. (a) Urine vitamin D binding protein (uVDBP). (b) Urine monocyte chemoattractant protein-1 (uMCP-1). (c) Urine interleukin-6 (uIL-6). (d) Urine interferon-gamma inducible protein-10 (uIP-10). (e) Serum interferon-gamma inducible protein-10 (sIP-10). (f) Serum interleukin-23 (sIL-23). Asterisk represents the p-value comparing the levels of responders and non-responders at each time point using the non-parametric Wilcoxon signed-rank test.

Fig. 2

Receiver operating characteristic (ROC) curves illustrate the predictive abilities of baseline urine interleukin-17 (uIL-17) and the changes in urine interleukin-6 (uIL-6), urine Interleukin-23 (uIL-23), and their combination at 3 months for predicting a 1-year response after induction therapy in patients with LN.