MALDI-MS imaging in the search for proteomic indicators of response to therapy in membranous nephropathy

Membranous Nephropathy (MN) is the most frequent cause of nephrotic syndrome in adults and the disease course is characterised by the “rule of third”, with one third of patients experiencing complete remission and the remaining experiencing relapses or progression of the disease. Additionally, the therapeutic approach is not standardised, leading to further heterogeneity in terms of response and outcome. In this pilot study, MALDI-MSI analysis was performed on renal biopsies obtained from two groups of patients, selected from 120 subjects with MN, which differentially responded to the range of immunosuppressive treatments administered. All the mass spectra were acquired in reflectron positive mode in the mass range of m/z 750 to 3500 using a rapifleX MALDI Tissuetyper™ with a pixel width and raster setting of 10µm, respectively. Three signals were determined to have a statistical significance when comparing the two patient groups (m/z 1111, 1198 and 1303) and had an altered signal intensity within glomeruli and tubular regions. Furthermore, the results highlighted the benefit of performing high spatial resolution MALD-MSI in the search prognostic markers of this frequent glomerulopathy. In particular, the signals that correlated with the response of the patient to the therapy could be spatially resolved within the different glomerular sub-structures and this localisation had a significant impact on the prognostic outlook of the patient. Despite much effort being made in recent years to understand the pathogenesis of MN, a panel of biomarkers able to predict the outcome of these patients following therapeutic treatment is still lacking. Here, we highlight a prospective panel of markers that can differentiate between these MN patients and could be a valuable starting point for a further study focused on verifying their predictive role in the treatment of Membranous Nephropathy