title: α-1-Antitrypsin detected by MALDI imaging in the study of glomerulonephritis: Its relevance in chronic kidney disease progression.
abstract: Idiopathic glomerulonephritis (GN), such as membranous glomerulonephritis, focal segmental glomerulosclerosis (FSGS), and IgA nephropathy (IgAN), represent the most frequent primary glomerular kidney diseases (GKDs) worldwide. Although the renal biopsy currently remains the gold standard for the routine diagnosis of idiopathic GN, the invasiveness and diagnostic difficulty related with this procedure highlight the strong need for new diagnostic and prognostic biomarkers to be translated into less invasive diagnostic tools. MALDI-MS imaging MALDI-MSI was applied to fresh-frozen bioptic renal tissue from patients with a histological diagnosis of FSGS (n = 6), IgAN, (n = 6) and membranous glomerulonephritis (n = 7), and from controls (n = 4) in order to detect specific molecular signatures of primary glomerulonephritis. MALDI-MSI was able to generate molecular signatures capable to distinguish between normal kidney and pathological GN, with specific signals (m/z 4025, 4048, and 4963) representing potential indicators of chronic kidney disease development. Moreover, specific disease-related signatures (m/z 4025 and 4048 for FSGS, m/z 4963 and 5072 for IgAN) were detected. Of these signals, m/z 4048 was identified as α-1-antitrypsin and was shown to be localized to the podocytes within sclerotic glomeruli by immunohistochemistry. α-1-Antitrypsin could be one of the markers of podocyte stress that is correlated with the development of FSGS due to both an excessive loss and a hypertrophy of podocytes.
authors.affiliation: Unit of Proteomics, Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors.forename: Andrew
authors.initials: A
authors.lastname: Smith
authors.affiliation: Unit of Pathology, Department of Surgery and Translational Medicine, University of Milano-Bicocca, Monza, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: L'Imperio
authors.affiliation: Unit of Proteomics, Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: De Sio
authors.affiliation: Unit of Pathology, Department of Surgery and Translational Medicine, University of Milano-Bicocca, Monza, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Ferrario
authors.affiliation: Unit of Pathology, Department of Surgery and Translational Medicine, University of Milano-Bicocca, Monza, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Scalia
authors.affiliation: Department of Pathology, San Raffaele Hospital, Milan, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Dell'Antonio
authors.affiliation: Unit of Nephrology, Department of Health Sciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Pieruzzi
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.|Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pontillo
authors.affiliation: Charité - Universitätsmedizin Berlin, Berlin, Germany.|Biomedical Research Foundation Academy of Athens, Athens, Greece.
authors.forename: Szymon
authors.initials: S
authors.lastname: Filip
authors.affiliation: Department of Nephrology, Medical Faculty, University of Skopje, Skopje, Macedonia.
authors.forename: Katerina
authors.initials: K
authors.lastname: Markoska
authors.affiliation: Department of Nephrology, Ospedale San Giovanni di Dio, Agrigento, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Granata
authors.affiliation: Department of Nephrology, Medical Faculty, University of Skopje, Skopje, Macedonia.
authors.forename: Goce
authors.initials: G
authors.lastname: Spasovski
authors.affiliation: Institute for Molecular Cardiovascular Research, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Jankowski
authors.affiliation: Department of Cardio-Thoracic and Respiratory Science, Second University of Naples, Naples, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Capasso
authors.affiliation: Unit of Pathology, Department of Surgery and Translational Medicine, University of Milano-Bicocca, Monza, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pagni
authors.affiliation: Unit of Proteomics, Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Magni
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D005922:Glomerulonephritis, IGA / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D000515:alpha 1-Antitrypsin / Q000302:isolation & purification* / Q000378:metabolism
chemical_list: D000515:alpha 1-Antitrypsin
keywords: Biomedicine; Biopsy; Glomerulonephritis; MALDI imaging; Mass spectrometry