Pathophysiology of glomerulonephritis in autoimmune diseases
Year: 2025
Type: article
Abstract: PURPOSE OF REVIEW: Autoimmune glomerulonephritis (GN) emerges when self-reactive humoral and cellular immunity converge in the kidney. Combined immunofluorescence and electron microscopy aids in classifying GN; however, more stratification strategies are required for personalized therapy. We aimed to review biopsy-anchored clinicopathologic classification and pathophysiology of GN-associated disorders based on immunofluorescence and electron microscopy. Additionally, we sought to integrate mechanistic insights from multiomics and spatial profiling that resolve the composition and spatial organization of the cellular "neighborhoods" that drive injury and repair across IgA vasculitis/nephropathy, lupus nephritis, antiglomerular basement membrane disease, and antineutrophil cytoplasmic antibody-associated vasculitis. RECENT FINDINGS: Although inciting antigens, immune complexes, and deposition patterns vary among entities, downstream injury pathways overlap. The convergent programs include complement activation, including locally produced renal complement, Fc receptor-driven myeloid effector functions, neutrophil extracellular traps with nucleic-acid sensing, the reprogramming of monocytes/macrophages, interleukin (IL)-23/IL-17, and type 1 interferon-primed cytotoxicity of T cells, and epithelial stress responses in podocytes and parietal epithelial cells. SUMMARY: Despite diverse triggers, autoimmune GNs share targetable injury pathways. Integrating biopsy-defined immune deposits and the accompanying inflammatory context with spatial, single-cell, and proteomic readouts enables mechanistic subtyping and pathway-aligned therapy. Tailoring treatment to individual dominant injury programs may improve renal outcomes and reduce adverse effects.
Source: Current Opinion in Rheumatology
Author: Kayaho Maeda
Institution: Nagoya University
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4415508337