Top-down proteomics of human saliva discloses significant variations of the protein profile in patients with mastocytosis.

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 in SM with (SM+C) or without (SM-C) additional cutaneous lesions and their classification is often challenging. This study 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 patient different from those of controls, a down-regulation of peptides/proteins involved in the mouth homeostasis and defense, as statherin, histatins, and acidic proline-rich proteins (aPRPs), and in innate immunity and inflammation, as the cathepsin inhibitors, suggesting a systemic condition associated to 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, α-defensins 1 and 4 in SM-C patients with respect to SM+C. Data are available via ProteomeXchange with identifier PXD017759.