Pauci-Immune Endocapillary Proliferative Glomerulonephritis With Glomerular M2 Macrophage Infiltration.

INTRODUCTION: Pauci-immune endocapillary proliferative glomerulonephritis (GN) (Pauci-I-EPGN) is a rare glomerular disease with a heterogeneous and poorly understood etiology. Here we describe the clinicopathological features, immune cell infiltration patterns, and treatment outcomes of Pauci-I-EPGN. METHODS: Fifteen patients with biopsy-proven Pauci-I-EPGN, diagnosed between January 2012 and June 2025, were studied retrospectively. RESULTS: Fifteen patients (7 males and 8 females) aged 50.1 ±13.0 years at renal biopsy were included. The median 24 hour urine protein was 2.00 g/d (0.30-7.77 g/d), with a median serum creatinine level of 1.14 mg/dL (0.54-5.36 mg/dL). Seven cases had prodromal infection. Light microscopy (LM) showed endocapillary proliferative lesions in glomeruli. Immunofluorescence (IF) staining was negative for IgG, IgA, IgM, component C3, component C1q, and light chains. Electron microscopy (EM) revealed no electron-dense deposits. Immunohistochemical staining showed that inflammatory cells in glomeruli were mainly cluster of differentiation CD68+ cells and a small number of CD3+ cells. Multiplex IF staining demonstrated that CD68+ CD163+ cells were the predominant infiltrating cell type in glomeruli. Extensive transforming growth factor-beta (TGF-β) expression was observed within glomeruli. Besides, urinary soluble CD163 levels normalized to urinary creatinine (u-Cr) were elevated in 12 patients and correlated with the number of glomerular CD68+ CD163+ macrophages. Among 11 patients with a median follow-up period of 16.4 months (0.6-80.5 months), 5 achieved complete remission, 2 achieved partial remission, 1 showed stable kidney function, and 3 had progressive renal disease (1 progressed to end-stage renal disease [ESRD]). CONCLUSION: Pauci-I-EPGN is a rare distinct entity characterized by abnormal activation of intraglomerular M2 macrophages and CD8+ T cell infiltration, with inflammation-fibrosis imbalance driven by TGF-β overexpression. Corticosteroids may offer a potential therapeutic benefit for this type of disease. The overall outcomes in this cohort were generally favorable.