PMID- 36813560 OWN - NLM STAT- Publisher LR - 20240216 IS - 1472-4146 (Electronic) IS - 0021-9746 (Linking) DP - 2023 Feb 22 TI - Spatial resolution of renal amyloid deposits through MALDI-MSI: a combined digital and molecular approach to monoclonal gammopathies. LID - jcp-2023-208790 [pii] LID - 10.1136/jcp-2023-208790 [doi] AB - AIMS: Identification and characterisation of monoclonal gammopathies of renal significance (MGRS) is critical for therapeutic purposes. Amyloidosis represents one of the most common forms of MGRS, and renal biopsy remains the gold standard for their classification, although mass spectrometry has shown greater sensitivity in this area. METHODS: In the present study, a new in situ proteomic technique, matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI), is investigated as an alternative to conventional laser capture microdissection MS for the characterisation of amyloids. MALDI-MSI was performed on 16 cases (3 lambda light chain amyloidosis (AL), 3 AL kappa, 3 serum amyloid A amyloidosis (SAA), 2 lambda light chain deposition disease (LCDD), 2 challenging amyloid cases and 3 controls). Analysis began with regions of interest labelled by the pathologist, and then automatic segmentation was performed. RESULTS: MALDI-MSI correctly identified and typed cases with known amyloid type (AL kappa, AL lambda and SAA). A 'restricted fingerprint' for amyloid detection composed of apolipoprotein E, serum amyloid protein and apolipoprotein A1 showed the best automatic segmentation performance (area under the curve >0.7). CONCLUSIONS: MALDI-MSI correctly assigned minimal/challenging cases of amyloidosis to the correct type (AL lambda) and identified lambda light chains in LCDD cases, highlighting the promising role of MALDI-MSI for amyloid typing. CI - (c) Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Bindi, Greta AU - Bindi G AD - Department of Medicine and Surgery, Proteomics and Metabolomics Units, University of Milano-Bicocca, Monza, Italy. FAU - Smith, Andrew AU - Smith A AD - Department of Medicine and Surgery, Proteomics and Metabolomics Units, University of Milano-Bicocca, Monza, Italy. FAU - Oliveira, Glenda AU - Oliveira G AD - Department of Medicine and Surgery, Proteomics and Metabolomics Units, University of Milano-Bicocca, Monza, Italy. FAU - Eccher, Albino AU - Eccher A AD - Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy. FAU - Vatrano, Simona AU - Vatrano S AD - Pathology Unit, ASP Catania, "Gravina" Hospital, Caltagirone, Italy. FAU - Alberici, Federico AU - Alberici F AD - Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili di Brescia, Brescia, Italy. FAU - Cazzaniga, Giorgio AU - Cazzaniga G AD - Department of Medicine and Surgery, Pathology, University of Milano-Bicocca, IRCCS Fondazione San Gerardo dei Tintori, Monza, Italy. FAU - Galimberti, Stefania AU - Galimberti S AD - Bicocca Bioinformatics Biostatistics and Bioimaging B4 Center, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. FAU - Capitoli, Giulia AU - Capitoli G AD - Bicocca Bioinformatics Biostatistics and Bioimaging B4 Center, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. FAU - Magni, Fulvio AU - Magni F AD - Department of Medicine and Surgery, Proteomics and Metabolomics Units, University of Milano-Bicocca, Monza, Italy. FAU - Pagni, Fabio AU - Pagni F AUID- ORCID: 0000-0001-9625-1637 AD - Department of Medicine and Surgery, Pathology, University of Milano-Bicocca, IRCCS Fondazione San Gerardo dei Tintori, Monza, Italy. FAU - L'Imperio, Vincenzo AU - L'Imperio V AUID- ORCID: 0000-0002-9284-2998 AD - Department of Medicine and Surgery, Pathology, University of Milano-Bicocca, IRCCS Fondazione San Gerardo dei Tintori, Monza, Italy vincenzo.limperio@gmail.com. LA - eng PT - Journal Article DEP - 20230222 PL - England TA - J Clin Pathol JT - Journal of clinical pathology JID - 0376601 SB - IM OTO - NOTNLM OT - amyloid OT - glomerulonephritis OT - hematology COIS- Competing interests: None declared. EDAT- 2023/02/23 06:00 MHDA- 2023/02/23 06:00 CRDT- 2023/02/22 21:42 PHST- 2023/01/17 00:00 [received] PHST- 2023/02/10 00:00 [accepted] PHST- 2023/02/22 21:42 [entrez] PHST- 2023/02/23 06:00 [pubmed] PHST- 2023/02/23 06:00 [medline] AID - jcp-2023-208790 [pii] AID - 10.1136/jcp-2023-208790 [doi] PST - aheadofprint SO - J Clin Pathol. 2023 Feb 22:jcp-2023-208790. doi: 10.1136/jcp-2023-208790.