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


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

SUBMITTER: Fava A 

PROVIDER: S-EPMC10906224 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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

Fava Andrea A   Buyon Jill J   Magder Laurence L   Hodgin Jeff J   Rosenberg Avi A   Demeke Dawit S DS   Rao Deepak A DA   Arazi Arnon A   Celia Alessandra Ida AI   Putterman Chaim C   Anolik Jennifer H JH   Barnas Jennifer J   Dall'Era Maria M   Wofsy David D   Furie Richard R   Kamen Diane D   Kalunian Kenneth K   James Judith A JA   Guthridge Joel J   Atta Mohamed G MG   Monroy Trujillo Jose J   Fine Derek D   Clancy Robert R   Belmont H Michael HM   Izmirly Peter P   Apruzzese William W   Goldman Daniel D   Berthier Celine C CC   Hoover Paul P   Hacohen Nir N   Raychaudhuri Soumya S   Davidson Anne A   Diamond Betty B   Petri Michelle M  

JCI insight 20240123 2


Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 patients with LN (573 samples) in the longitudinal Accelerating Medicines Partner  ...[more]

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