Serum NF-κB-Regulated Biomarkers of Proliferative Lupus Nephritis

Introduction: Lupus nephritis (LN) is kidney inflammation that commonly occurs from systemic lupus erythematosus. NF-κB activity is increased in LN patients, leading to elevated circulating concentrations of immune modulators that contribute to LN pathophysiology. This study sought to investigate this phenomenon with the aim of discovering novel serum biomarkers for LN. Methods: A multiplex antibody-based assay was performed with serum from 24 LN patients and 7 healthy controls (HCs) to determine if 48 NF-κB-regulated proteins were elevated in LN patients. Confirmation ELISAs were performed on stem cell factor (SCF), macrophage colony-stimulating factor (M-CSF), and interleukin-2 receptor alpha (IL-2Rα) subunit in a separate sample cohort of 27 LN patients and 10 HC. Follow-up ELISAs were performed on samples obtained from the same patients during LN remission to determine if these candidates were reliable predictors of disease activity. Comparisons of protein levels between LN patients and HC were performed using a series of 2-tailed Mann-Whitney tests. Paired samples were analyzed using a Wilcoxon matched pairs test. Two-tailed Spearman’s correlation analyses were used to compare serum protein concentrations with LN clinical parameters. All p values were adjusted for multiple comparisons. Results: SCF, M-CSF, and IL-2Rα were significantly elevated in LN serum. Elevated serum SCF and M-CSF were significantly correlated with elevated urine protein to creatinine ratio, decreased estimated glomerular filtration rate, and elevated serum creatinine. Elevated serum IL-2Rα was significantly correlated with elevated serum creatinine. Serum SCF concentration was significantly decreased during LN remission in paired samples from individuals, but it was not a good predictor at the population level (AUC = 0.6265). Conclusion: We identified the NF-κB-regulated proteins SCF, M-CSF, and IL-2Rα as candidate serum biomarkers for consideration in monitoring LN activity. Our findings also indicate the importance for follow-up mechanistic studies pertaining to these inflammatory mediators.