MALDI mass spectrometry imaging unravels organ and amyloid‐type specific peptide signatures in pulmonary and gastrointestinal amyloidosis

Abstract

Purpose Amyloidosis is a disease group caused by pathological aggregation and deposition of peptides in diverse tissue sites. Recently, matrix‐assisted laser desorption/ionization mass spectrometry imaging coupled with ion mobility separation (MALDI‐IMS MSI) was introduced as a novel tool to identify and classify amyloidosis using single sections from formalin‐fixed and paraffin‐embedded cardiac biopsies. Here, we tested the hypothesis that MALDI‐IMS MSI can be applied to lung and gastrointestinal specimens. Experimental Design Forty six lung and 65 gastrointestinal biopsy and resection specimens with different types of amyloid were subjected to MALDI‐IMS MSI. Ninety three specimens included tissue areas without amyloid as internal negative controls. Nine cases without amyloid served as additional negative controls. Results Utilizing a peptide filter method and 21 known amyloid specific tryptic peptides we confirmed the applicability of a universal peptide signature with a sensitivity of 100% and a specificity of 100% for the detection of amyloid deposits in the lung and gastrointestinal tract. Additionally, the frequencies of individual m/z‐values of the 21 tryptic marker peptides showed organ‐ and tissue‐type specific differences. Conclusions and Clinical Relevance MALDI‐IMS MSI adds a valuable analytical approach to diagnose and classify amyloid and the detection frequency of individual tryptic peptides is organ‐/tissue‐type specific.

Amyloidosis: What does pathology offer? The evolving field of tissue biopsy

“…Recently, however, other authors have proposed slightly different amyloid signatures: Misra et al ( 81 ) indicated ApoE, SAP, and glycosaminoglycans; Benson et al ( 1 ) proposed ApoE, SAP and heparan sulfate proteoglycan; Schumann et al ( 82 ), using a new proteomics approach based on MALDI imaging, have found an even more elaborate signature composed of ApoE, SAP, Apolipoprotein A-1, Vitronectin, and SAA.…”

“…Nanometric spatial resolution, however, is still impossible with MSI at its present level of development and technical improvements are needed for its successful application in clinical pathology ( 82 ).…”

Dissecting the Molecular Features of Systemic Light Chain (AL) Amyloidosis: Contributions from Proteomics

“…Additional important knowledge is also being provided by another proteomic approach, MALDI imaging mass spectrometry (IMS). This technology possesses the unique capability of allowing direct MS analysis of histology sections, thereby preserving the spatial distribution of proteins [92,94,95]. MALDI-IMS studies allow demonstrating the co-localization of amyloid-associated proteins with Congo Red-positive areas, but are also disclosing differences in the peptides with which amyloid-associated species are identified in different amyloidosis types and tissues.…”

“…MALDI-IMS studies allow demonstrating the co-localization of amyloid-associated proteins with Congo Red-positive areas, but are also disclosing differences in the peptides with which amyloid-associated species are identified in different amyloidosis types and tissues. The MALDI-IMS distribution of peptides from a set of amyloid-associated proteins (e.g., ApoE, SAP, VTN) has in fact been proposed as part of a possible strategy for amyloid typing [94], since specific peptide ions create a type and organ specific MALDI-IMS signature [95]. These observations may relate to distinct conformation, abundance or localization of these molecular species, opening unprecedented questions and new perspectives in the study of amyloidoses.…”

N-terminal peptide fragment constitutes core of amyloid deposition of serum amyloid A: An imaging mass spectrometry study

“…Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) [4,5] has recently been used to identify and characterize amyloid precursor proteins directly on thin tissue sections, such as tissue microarrays. This new technique has been used to identify systemic amyloidosis [6][7][8][9] and amyloid-β deposits in the human brain [10,11]. In Alzheimer's disease or cerebral amyloid angiopathy, the distribution of truncated C-terminal fragments of amyloid-β is altered in the brain tissue, as visualized by MALDI-Time Of Flight (TOF) MS [10,11].…”