1. MALDI imaging in Fabry nephropathy: a multicenter study
- Author
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Viviana Scollo, Vincenzo L'Imperio, Andrew Smith, Federico Pieruzzi, Antonella Tosoni, Manuela Nebuloni, Maria D'Armiento, Antonio Pisani, Fulvio Magni, Renato Alberto Sinico, Fabio Pagni, Stefano Casano, L'Imperio, V, Smith, A, Pisani, A, D'Armiento, M, Scollo, V, Casano, S, Sinico, R, Nebuloni, M, Tosoni, A, Pieruzzi, F, Magni, F, Pagni, F, L'Imperio, V., Smith, A., Pisani, A., D'Armiento, M., Scollo, V., Casano, S., Sinico, R. A., Nebuloni, M., Tosoni, A., Pieruzzi, F., Magni, F., and Pagni, F.
- Subjects
Adult ,Male ,Proteomics ,Nephrology ,MALDI imaging ,medicine.medical_specialty ,Pathology ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Nephropathy ,Fabry nephropathy ,Young Adult ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Internal medicine ,Biopsy ,medicine ,Humans ,Aged ,Retrospective Studies ,Proteinuria ,medicine.diagnostic_test ,business.industry ,Proteomic ,Histology ,Middle Aged ,medicine.disease ,Phenotype ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Mutation ,Fabry Disease ,Female ,Kidney Diseases ,Renal biopsy ,medicine.symptom ,business - 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-alpha (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.
- Published
- 2019
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