Cell Adhesion Molecules (CAMs), NrCAM and P-Cadherin, as Emerging Biomarkers of Lupus Nephritis

Background: Lupus nephritis (LN) is a severe renal complication of systemic lupus erythematosus, marked by immune-driven inflammation and glomerular injury. Cell adhesion molecules (CAMs), which mediate cell-to-cell interactions, have emerged as key biomarkers linked to LN-related inflammation and damage. This study used a protein microarray to identify novel serum biomarkers and assess their diagnostic and pathogenic relevance in LN. Methods: Human serum samples from LN, chronic kidney disease (CKD), and healthy control (HC) cohorts were analyzed using a multiplex antibody-based protein microarray to profile a panel of CAMs. Differential expression analyses combined with machine learning techniques (LASSO regression) identified key biomarkers with the highest diagnostic potential. Selected candidates were validated in a larger, independent cohort using ELISA. Biomarker levels were correlated with clinicopathological parameters, including proteinuria, eGFR, and histologic class. Results: NrCAM and P-Cadherin emerged as the most promising biomarkers, significantly distinguishing LN from HC (n=50 LN, 21 HC, 10 CKD). NrCAM levels were 2.5-fold higher in LN vs HC (p<0.0001) and 1.6-fold higher in LNA vs LNI (n=37 LNA, 13 LNI; p<0.01). P-Cadherin was upregulated in LN vs HC (p<0.0001), and also differentiated CKD (p<0.001) and LNA from LNI (p<0.01). Both markers showed strong diagnostic potential, with AUC values of 0.92 (NrCAM) and 0.82 (P-Cadherin). Significant correlations with SLEDAI, rSLEDAI, and histological indices further underscored their relevance to LN severity and activity. NrCAM and P-Cadherin are complementary in reflecting renal pathology changes, including endocapillary hypercellularity, cellular crescents, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Conclusion: NrCAM and P-Cadherin are promising non-invasive biomarkers for LN diagnosis. Their ability to distinguish between disease states and correlate with clinical parameters highlights their potential to improve patient stratification and guide personalized treatment approaches in LN.Boxplots and heatmap show elevated NrCAM and P-cadherin levels in LN and CKD vs HC, and their correlations with clinical and histological LN features.