Membranous Nephropathy (MN) is an immunocomplex mediated renal disease that represents the leading cause of nephrotic syndrome in adults and is 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 management of patients. In secondary cases, the best strategy consists in treating the underlying disease whereas in primary forms, the possible 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 useful biomarkers to help further stratify these two different forms of glomerulopathy seems mandatory. Here, MALDI-MSI was applied to formalin-fixed paraffin-embedded (FFPE) renal biopsies from histologically diagnosed primary and secondary MN patients (n=20) in order to evaluate the capability of this technology 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, this proteomic approach detected a number of signals that could differentiate the different forms of iMN that were positive to PLA2R or IgG4 as well as a further set of signals (m/z 1094, 1116, 1381 and 1459) that distinguish these patients from those who were negative to both. These signals could potentially represent future targets to be investigated as proteomic markers 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
Smith, A., L'Imperio, V., Ajello, E., Ferrario, F., Mosele, N., Stella, M., et al. (2017). The putative role of MALDI-MSI in the study of Membranous Nephropathy. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 1865(7), 865-874 [10.1016/j.bbapap.2016.11.013].
The putative role of MALDI-MSI in the study of Membranous Nephropathy
Smith, A;L'Imperio, V;Ajello, E;Stella, M;Galli, M;Chinello, C;Pieruzzi, F;Pagni, F;Magni, F
2017
Abstract
Membranous Nephropathy (MN) is an immunocomplex mediated renal disease that represents the leading cause of nephrotic syndrome in adults and is 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 management of patients. In secondary cases, the best strategy consists in treating the underlying disease whereas in primary forms, the possible 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 useful biomarkers to help further stratify these two different forms of glomerulopathy seems mandatory. Here, MALDI-MSI was applied to formalin-fixed paraffin-embedded (FFPE) renal biopsies from histologically diagnosed primary and secondary MN patients (n=20) in order to evaluate the capability of this technology 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, this proteomic approach detected a number of signals that could differentiate the different forms of iMN that were positive to PLA2R or IgG4 as well as a further set of signals (m/z 1094, 1116, 1381 and 1459) that distinguish these patients from those who were negative to both. These signals could potentially represent future targets to be investigated as proteomic markers 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
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