Salivary Cystatin D Interactome in Patients with Systemic Mastocytosis: An Exploratory Study

Mastocytosis, a rare blood disorder characterized by the proliferation of clonal abnormal mast cells, has variegated clinical spectrum and diagnosis is often difficult delayed. Recently we proposed cathepsin inhibitor cystatin D-R26 as salivary candidate biomarker systemic mastocytosis (SM). Its C26 variant able to form multiprotein complexes (mPCs) since protein–protein interactions (PPIs) are crucial for studying disease pathogenesis, potential markers, therapeutic targets, aimed define protein composition D-C26 interactome associated with SM. An exploratory affinity purification-mass spectrometry method was applied on pooled samples from SM patients, patient subgroups without cutaneous symptoms (SM+C SM−C), healthy controls (Ctrls). Interactors specifically detected in Ctrls were found be implicated networks cell tissue homeostasis, innate system, endopeptidase regulation, antimicrobial protection. distinctive SM−C patients participate PPI related glucose metabolism, S-nitrosylation, antibacterial humoral response, neutrophil degranulation, while interactors specific SM+C mainly epithelial keratinocyte differentiation, cytoskeleton rearrangement, immune response pathways. Proteins sensitive redox changes, well proteins immunomodulatory properties activating identified patients; many them involved directly process activation. Although preliminary, these results demonstrate that alterations provide basis future investigations based quantitative proteomic analysis validation.