title: The putative role of MALDI-MSI in the study of Membranous Nephropathy.
abstract: Membranous Nephropathy (MN) is an immunocomplex mediated renal disease that represents one of the most frequent glomerulopathies worldwide. This glomerular disease can manifest as primary (idiopathic) or secondary and this distinction is crucial when choosing the most appropriate course of treatment. In secondary cases, the best strategy involves treating the underlying disease, whereas in primary forms, the identification of confirmatory markers of the idiopathic etiology underlining the process is requested by clinicians. Among those currently reported, the positivity to circulating antigens (PLA2R, IgG4 and THSD7A) was demonstrated in approximately 75% of iMN patients, while approximately 1 in 4 patients with iMN still lack a putative diagnostic marker. Ultimately, the discovery of biomarkers to help further stratify these two different forms of glomerulopathy seems mandatory. Here, MALDI-MSI was applied to FFPE renal biopsies from histologically diagnosed primary and secondary MN patients (n=20) in order to detect alterations in their tissue proteome. MALDI-MSI was able to generate molecular signatures of primary and secondary MN, with one particular signal (m/z 1459), identified as Serine/threonine-protein kinase MRCK gamma, being over-expressed in the glomeruli of primary MN patients with respect to secondary MN. Furthermore, a number of signals that could differentiate the different forms of iMN that were positive to PLA2R or IgG4 were detected, as well as a further set of signals (m/z 1094, 1116, 1381 and 1459) that could distinguish these patients from those who were negative to both. These signals could potentially represent future targets for the further stratification of iMN patients. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.
authors.affiliation: Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Monza, Italy.
authors.forename: Andrew
authors.initials: A
authors.lastname: Smith
authors.affiliation: Department of Medicine and Surgery, Pathology, University of Milano-Bicocca, San Gerardo Hospital, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: L'Imperio
authors.affiliation: Department of Medicine and Surgery, Nephrology Unit, University of Milano-Bicocca, Monza, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Ajello
authors.affiliation: Department of Medicine and Surgery, Pathology, University of Milano-Bicocca, San Gerardo Hospital, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Ferrario
authors.affiliation: Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Monza, Italy.
authors.forename: Niccolò
authors.initials: N
authors.lastname: Mosele
authors.affiliation: Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Monza, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Stella
authors.affiliation: Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Monza, Italy.
authors.forename: Manuel
authors.initials: M
authors.lastname: Galli
authors.affiliation: Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Monza, Italy.
authors.forename: Clizia
authors.initials: C
authors.lastname: Chinello
authors.affiliation: Department of Medicine and Surgery, Nephrology Unit, University of Milano-Bicocca, Monza, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Pieruzzi
authors.affiliation: Department of Nephrology, Medical Faculty, University of Skopje, Skopje, Macedonia.
authors.forename: Goce
authors.initials: G
authors.lastname: Spasovski
authors.affiliation: Department of Medicine and Surgery, Nephrology Unit, University of Milano-Bicocca, Monza, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pagni
authors.affiliation: Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Monza, Italy. Electronic address: fulvio.magni@unimib.it.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Magni
mesh_terms: D000941:Antigens / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy / Q000379:methods; D015433:Glomerulonephritis, Membranous / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D054507:Receptors, Phospholipase A2 / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D019699:Thrombospondins / Q000378:metabolism
chemical_list: D000941:Antigens; D015415:Biomarkers; D007074:Immunoglobulin G; C516360:PLA2R1 protein, human; D020543:Proteome; D054507:Receptors, Phospholipase A2; C546399:THSD7A protein, human; D019699:Thrombospondins; D017346:Protein Serine-Threonine Kinases
keywords: FFPE; Kidney; MALDI-Imaging; Mass Spectrometry Imaging; Membranous Nephropathy