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

Simone Serrao,M Teresa Sanna,Irene Messana,Stefano Del Giacco,Alessandra Olianas,Federica Iavarone,Francisco Amado,Margherita Deidda,Massimo Castagnola,Tiziana Cabras,Davide Firinu,Cristina Contini,Mozhgan Boroumand,Barbara Manconi

doi:10.1021/acs.jproteome.0c00207

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.

Highlights

Mastocytosis is an anomalous clonal proliferation and accumulation of mast cells in various tissues[1] with an estimate prevalence of 1 case per 10,000 people.[2]
To analyze the salivary samples by RP-HPLC-ESI-MS, whole saliva collected from healthy subjects and patients was treated with trifluoroacetic acid (TFA) aqueous solution
RP-HPLCESI-MS top-down analysis of the acid-soluble fraction of human saliva allowed detecting the proteins/peptides, and their posttranslational modifications (PTMs) derivatives are reported in Table 2, as well as performing a comparative label-free quantification of these components in different sets of samples

Summary

Introduction

Mastocytosis is an anomalous clonal proliferation and accumulation of mast cells in various tissues[1] with an estimate prevalence of 1 case per 10,000 people.[2]. SM usually develops in adults and it is characterized by infiltration of mast cells in various internal organs, such as bone marrow and the gastrointestinal tract.[1,4]

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Conclusion