Top-Down Proteomics of Human Saliva Discloses Significant Variations of the Protein Profile in Patients with Mastocytosis

Abstract

Mastocytosis is a myeloproliferative neoplasm causing abnormal clonal mast cell accumulation in different tissues, such as skin and bone marrow. A cutaneous subtype (CM) is distinguished from a systemic one (SM); SM patients can be grouped into SM with (SM+C) or without (SM-C) additional cutaneous lesions, and their classification is often challenging. This study was purposed to highlight variations in the salivary proteome of patients with different mastocytosis subtypes and compared to healthy controls. A top-down proteomics approach coupled to a label-free quantitation revealed salivary profiles in patients different from those of controls and a down-regulation of peptides/proteins involved in the mouth homeostasis and defense, such as statherin, histatins, and acidic proline-rich proteins (aPRPs), and in innate immunity and inflammation, such as the cathepsin inhibitors, suggesting a systemic condition associated with an exacerbated inflammatory state. The up-regulation of antileukoproteinase and S100A8 suggested a protective role against the disease status. The two SM forms were distinguished by the lower levels of truncated forms of aPRPs, statherin, P-B peptide, and cystatin D and the higher levels of thymosin β4 and α-defensins 1 and 4 in SM-C patients with respect to SM+C. Data are available via ProteomeXchange with identifier PXD017759.

Top-Down Proteomics of Human Saliva Highlights Anti-inflammatory, Antioxidant, and Antimicrobial Defense Responses in Alzheimer Disease

“…Thirty microliters of acidic extracts were injected in HPLC/low-resolution ESI-MS, applying procedures and conditions optimized in our previous studies ( Contini et al, 2020 ; Serrao et al, 2020 ). The total ion current (TIC) chromatographic profiles were analyzed to selectively search and quantify the peptides/proteins reported in Supplementary Table 2 ( Supplementary Material ), which shows UniProtKB codes, elution times, and experimental and theoretical average mass values (Mav) of the proteins/peptides included in the study.…”

Top-Down Proteomics Detection of Potential Salivary Biomarkers for Autoimmune Liver Diseases Classification

“…The UniProt-KB code, experimental and theoretical average mass values (Mav), elution times of proteins and peptides analyzed, m/z values and charge of the multiple-charged ions selected for eXtracted Ion Current (XIC) searches in HPLC-low resolution MS and PTMs are reported in Table S1 . All the proteins/peptides listed in Table S1 have been previously characterized by high-resolution tandem MS analysis [ 41 , 42 ].…”

Saliva, a bodily fluid with recognized and potential diagnostic applications

“…The study by Serrao et al aimed to highlight variations in the salivary proteome of patients with different mastocytosis subtypes compared to healthy controls. The top-down proteomics approach coupled to a label-free quantitation revealed different salivary profiles in patients compared to controls, highlighting in particular, a downregulation of peptides/proteins involved in homeostasis and defense of the oral cavity, such as statherin, histatins, and acidic prolinerich proteins (aPRPs), as well as in innate immunity and inflammation, such as the cathepsin inhibitors, suggesting a systemic condition associated with an exacerbated inflammatory state [52].…”

“…The upregulation of antileukoproteinase and S100A8 suggested a protective role against the disease status. The two SM forms were distinguished by the lower levels of truncated forms of aPRPs, statherin, P‐B peptide, and cystatin D and the higher levels of thymosin β4 and α‐defensins 1 and 4 in SM‐C patients with respect to SM+C [ 52 ]. However, no early disease‐specific biomarkers revealed by top‐down platforms have so far been transferred into clinical practice.…”