Vincenzo L'Imperio1, Andrew Smith2, Antonio Pisani3, Maria D'Armiento4, Viviana Scollo5, Stefano Casano1, Renato Alberto Sinico5, Manuela Nebuloni6,7, Antonella Tosoni6,7, Federico Pieruzzi5, Fulvio Magni2, Fabio Pagni8,9. 1. Department of Medicine and Surgery, Pathology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy. 2. Department of Medicine and Surgery, Clinical Proteomics and Metabolomics Unit, University of Milano-Bicocca, Monza, Italy. 3. Chair of Nephrology, University Federico II, Naples, Italy. 4. Department of Biomorphological and Functional Sciences, Section of Anatomic Pathology, Federico II University, Naples, Italy. 5. Department of Medicine and Surgery, Nephrology Unit, University of Milano-Bicocca, Monza, Italy. 6. Research Center for Renal Immunopathology, University of Milan, Milan, Italy. 7. Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy. 8. Department of Medicine and Surgery, Pathology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy. fabio.pagni@unimib.it. 9. Research Center for Renal Immunopathology, University of Milan, Milan, Italy. fabio.pagni@unimib.it.
Abstract
BACKGROUND: The current study evaluates the application of histology and in situ proteomics (MALDI-MSI) in Fabry nephropathy (FN), showing investigative and classification role for this coupled approach. METHODS: A retrospective series of 14 formalin fixed paraffin embedded (FFPE) renal biopsies with diagnosis of FN and 1 biopsy from a patient bearing a galactosidase-α (GLA) genetic variant of unknown significance (GVUS, c.376A>G) have been classified for clinical characteristics. Groups were compared for histological differences (following the ISGFN scoring system). Moreover, renal biopsies from these cases have been analyzed with MALDI-MSI as previously described to find proteomic signatures among different mutations and phenotypes. RESULTS: Comparison of clinical features revealed lower mean 24 h proteinuria in females (225 mg/24 h) than in males (1477.5 mg/24 h, p = 0.006). As for clinical characteristics, females significantly differed from males only for lower arterial sclerosis, with a mean value of 0.82 vs. 1.05 (p = 0.001). Proteomic analysis demonstrated specific signatures in different subgroups of FN patients. Moreover, MALDI correctly classified cases with undetermined mutation or GVUS. CONCLUSIONS: The present study demonstrated the feasible application of MALDI-MSI in the analysis of FN FFPE renal biopsies, allowing the detection of putative signatures for phenotypic distinction and demonstrating genetic classification capabilities.
BACKGROUND: The current study evaluates the application of histology and in situ proteomics (MALDI-MSI) in Fabry nephropathy (FN), showing investigative and classification role for this coupled approach. METHODS: A retrospective series of 14 formalin fixed paraffin embedded (FFPE) renal biopsies with diagnosis of FN and 1 biopsy from a patient bearing a galactosidase-α (GLA) genetic variant of unknown significance (GVUS, c.376A>G) have been classified for clinical characteristics. Groups were compared for histological differences (following the ISGFN scoring system). Moreover, renal biopsies from these cases have been analyzed with MALDI-MSI as previously described to find proteomic signatures among different mutations and phenotypes. RESULTS: Comparison of clinical features revealed lower mean 24 h proteinuria in females (225 mg/24 h) than in males (1477.5 mg/24 h, p = 0.006). As for clinical characteristics, females significantly differed from males only for lower arterial sclerosis, with a mean value of 0.82 vs. 1.05 (p = 0.001). Proteomic analysis demonstrated specific signatures in different subgroups of FN patients. Moreover, MALDI correctly classified cases with undetermined mutation or GVUS. CONCLUSIONS: The present study demonstrated the feasible application of MALDI-MSI in the analysis of FN FFPE renal biopsies, allowing the detection of putative signatures for phenotypic distinction and demonstrating genetic classification capabilities.
Authors: Gabriele De Sio; Andrew James Smith; Manuel Galli; Mattia Garancini; Clizia Chinello; Francesca Bono; Fabio Pagni; Fulvio Magni Journal: Mol Biosyst Date: 2015-06
Authors: Maarten Arends; Christoph Wanner; Derralynn Hughes; Atul Mehta; Daniel Oder; Oliver T Watkinson; Perry M Elliott; Gabor E Linthorst; Frits A Wijburg; Marieke Biegstraaten; Carla E Hollak Journal: J Am Soc Nephrol Date: 2016-12-15 Impact factor: 10.121