MassIVE MSV000092309

Partial Public PXD043405

Towards the definition of the molecular hallmarks of Idiopathic Membranous Nephropathy in serum proteome: a DIA-PASEF approach

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Description

Idiopathic Membranous Nephropathy (IMN) is a pathologically defined disorder of the glomerulus, primarily responsible for nephrotic syndromes (NS) in nondiabetic adults. The underlying molecular mechanisms are still not completely clarified. To explore possible molecular and functional signatures, an optimised MS-method based on next-generation data-independent-acquisition combined with ion-mobility was applied to serum of patients affected by IMN (n=15) or by other glomerulopathies (PN) (n=15). The statistical comparison highlighted a panel of 57 de-regulated proteins with a significant increase of lipoprotein-related-proteins (APOC1, APOB, APOA1, APOL1 and LCAT) and a substantial quantitative alteration of key serpins (including A4, D1, A7, A6, F2, F1 and 1) possibly associated to IMN or NS and podocyte stress. A critical dysregulation in metabolisms of lipids (e.g.VLDL assembly and clearance) likely to be related to known hyperlipidemia in IMN, along with involvement of non-classical complement pathways and a putative enrolment of ficolin-2 in sustaining the activation of the lectin-mediated complement system have been pinpointed. Moreover, Mannose Receptor CD206 (MRC1-down in IMN) and biotinidase (BTD-up in IMN) are able alone to accurately distinguish IMN vs PN. To conclude, our work provides key proteomic insights into the IMN complexity, opening the way to an efficient stratification of MN patients. Herein, a tailor-made DIA-PASEF method was applied to quali-quantitatively portray undepleted serum proteome collected from 15 IMN patients and 15 gender- and age-matched nephropathic subjects having a similar presentation but a different aetiology (PN). For each sample, 400 ng of peptides were injected in duplicate into Evosep One (Evosep Biosystems, Odense, Denmark) LC system coupled online with timsTOF fleXTM (Bruker Daltonics, Bremen, Germany) mass spectrometer (60runs in total). Raw data were elaborated by using SpectronautTM (v.17, https://biognosys.com) following a library-free processing method. [doi:10.25345/C51R6N99X] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Membranous Nephropathies ; Proteomics ; Mass spectrometry ; DIA-PASEF ; Serum

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Principal Investigators:
(in alphabetical order) 		Clizia Chinello, UNIMIB, Italy
Submitting User: fulvio_magni
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