The Identification of Urinary Proteins as Markers of Disease Activity in Childhood-onset SLE

The objective of this study was to evaluate the performance of urine CD36, FCGR2α, FCLR5, ferritin, IL2Rβ, LAIR2, L-Selectin, MCSFR, NCAM-1, and TGFβ for detecting disease activity in childhood-onset systemic lupus erythematosus (cSLE) patients. Sixty consecutive pediatric patients fulfilling ≥ 4 ACR criteria for SLE and twenty healthy controls were recruited for testing of ten urinary proteins by enzyme-linked immunosorbent assay. Disease activity was assessed using SLEDAI-2000. Urine CD36, FCLR5, ferritin, L-Selectin, M-CSFR, and NCAM-1 had significantly increased concentration levels in active renal patients in comparison to all other cohorts, which shows high potential for the proteins to act as biomarkers for SLE disease activity within a pediatric cohort. L-Selectin, M-CSFR, CD36, FCRL5, NCAM-1, and ferritin presented with excellent AUC values, respectively ranging between 0.96 and 0.89 (P<0.0001). Lupus nephritis patients were ascertained by biopsy activity and chronicity indices. FCLR5, ferritin, L-Selectin, M-CSFR, and NCAM-1 positively correlated with SLEDAI and renal SLEDAI (rSLEDAI) (P<0.0001). MCSFR and NCAM-1 were further investigated to have strong correlations with various pathology metrics outperforming the other protein markers as well as conventional metrics like double-stranded DNA (dsDNA) and complement C3. Urine L-Selectin, M-CSFR, CD36, FCRL5, NCAM-1, and ferritin, showed high ROC AUC values, sensitivities, and specificities indicating a strong ability to accurately distinguish between active renal and inactive SLE patients. Continued focus on these urinary proteins within longitudinal studies would further validate the clinical utility of these biomarkers in tracking kidney disease activity and progression in children with lupus nephritis. ***This project was completed with contributions from M. John Hicks and Scott E. Wenderfer from Texas Children's Hospital and Baylor College of Medicine.