Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis

• DOI: 10.1172/jci.insight.172569
• Publication Date: 2024-01-22T19:00:38Z
• Authors: Andrea Fava; Jill Buyon; Laurence Magder; Jeff Hodgin; Avi Rosenberg; Dawit S. Demeke; Deepak A. Rao; Arnon Arazi; Alessandra Ida Celia; Chaim Putterman; Jennifer H. Anolik; Jennifer Barnas; Maria Dall’Era; David Wofsy; Richard Furie; Diane Kamen; Kenneth Kalunian; Judith A. James; Joel Guthridge; Mohamed G. Atta; Jose Monroy Trujillo; Derek Fine; Robert Clancy; H. Michael Belmont; Peter Izmirly; William Apruzzese; Daniel Goldman; Celine C. Berthier; Paul Hoover; Nir Hacohen; Soumya Raychaudhuri; Anne Davidson; Betty Diamond; Michelle Petri
• Keywords: Proteomics; Inflammation; Autoimmunity; Diagnostics; Lupus; Nephrology; Proteomics; 610; Lupus; 600; Autoimmunity; Lupus Nephritis; Aggression; Proteinuria; Nephrology; Humans; Diagnostics; Research Article

Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond treatment. Noninvasive biomarkers intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts inflammation, we studied proteomic profiles 225 with LN (573 samples) in longitudinal Accelerating Medicines Partnership RA/SLE cohort. Urinary monocyte/neutrophil degranulation (i.e., PR3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation CD163, CD206, galectin-1), wound healing/matrix degradation nidogen-1, decorin), IL-16 characterized aggressive proliferative classes significantly correlated histological activity. A decline these after 3 months treatment predicted 1-year response robustly than proteinuria, standard care (AUC: CD206 0.91, EGFR 0.9, CD163 0.89, proteinuria 0.8). Candidate were validated provide potentially treatable targets. We propose immunological activity noninvasive tools diagnose surrogate endpoints for clinical trials. These findings insights into processes involved This data set public resource generate test hypotheses validate biomarkers.