IL-33 as a biomarker of active MPO-ANCA associated glomerulonephritis

Myeloperoxidase (MPO)-ANCA–associated glomerulonephritis (MPO-AAGN) is a severe inflammatory kidney disease for which reliable biomarkers for disease activity assessment remains limited. We measured plasma and urinary interleukin-33 (IL-33) levels by ELISA in 80 MPO-AAGN patients and 20 healthy controls and evaluated their associations with the Birmingham Vasculitis Activity Score (BVAS), inflammatory markers, renal function indices, MPO-ANCA, and renal histopathology. IL-33 levels were higher in MPO-AAGN patients than in controls (plasma 393 ± 241, 230 ± 158 pg/mL, P = 0.0051; urine 500 ± 314, 277 ± 229 pg/mL, P = 0.0060). The plasma IL-33 concentration was correlated with the BVAS (ρ = 0.64; P < 0.001), remained independently associated with disease activity after multivariable adjustment, and improved the model performance beyond that of conventional clinical variables. Urinary IL-33 showed similar associations and were correlated with neutrophil-related indices. High IL-33 levels were associated with CD15⁺ neutrophil infiltration and active renal histopathological lesions, including fibrinoid necrosis and acute tubulointerstitial inflammation. Single-cell RNA sequencing suggested predominant endothelial IL-33 expression, suggesting that circulating and urinary IL-33 levels are associated with inflammatory activity and renal injury in MPO-AAGN patients and identifying IL-33 as a candidate biomarker associated with disease activity. Prospective multicenter studies are needed to establish its incremental clinical value beyond that of existing biomarkers.