Mass Spectrometry With Data-Independent Acquisition for the Identification of Target Antigens in Membranous Nephropathy

作者：Johann Morelle, Selda Aydın, Hanna Dêbiec, Nathalie Demoulin, Inès Dufour, Manon Martin, Laurent Gatto, Didier Vertommen, Pierre Ronco · 发表于：American Journal of Kidney Diseases · 年份：2025 · DOI：10.1053/j.ajkd.2025.01.014 · 被引用次数：8 · 研究领域：Renal Diseases and Glomerulopathies、Advanced Proteomics Techniques and Applications、Renal Transplantation Outcomes and Treatments

RATIONALE & OBJECTIVE: In recent years, the strategy of using laser capture microdissection and mass spectrometry (LCM/MS) has expanded the landscape of antigens associated with membranous nephropathy (MN). Specific associations with phenotypes, diseases, and sometimes reversible triggers led to an antigen-based classification of MN, informing precision medicine and highlighting the potential value of routine use of proteomics in classifying MN. This study reproduces and further improves the original LCM/MS for antigen detection in MN. STUDY DESIGN: Retrospective cohort study using residual material from kidney biopsies. SETTING & PARTICIPANTS: R-negative MN; and 5 individuals with other glomerular diseases. PREDICTOR: Proteomic analysis of microdissected glomeruli. OUTCOME: R-negative MN. ANALYTICAL APPROACH: The technique of LCM/MS was expanded by integrating a data-independent acquisition (DIA) approach to enable the identification and quantification of peptides of varying abundance. RESULTS: R-negative MN. LIMITATIONS: Retrospective design; sample size; no identification of novel antigens. CONCLUSIONS: An integrative approach combining LCM/MS and DIA enabled identification of more target antigens than LCM/MS with DDA, potentially informing our understanding of disease mechanisms in MN. PLAIN-LANGUAGE SUMMARY: Membranous nephropathy is an autoimmune kidney disease characterized by circulating autoantibodies that recognize antigens in podocytes or in the glomerular basement...