{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:31:18Z","timestamp":1760149878792,"version":"build-2065373602"},"reference-count":69,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Cagliari","award":["FIR-2019","FIR 2020 Cabras Tiziana","FIR 2019 Alessandra Olianas"],"award-info":[{"award-number":["FIR-2019","FIR 2020 Cabras Tiziana","FIR 2019 Alessandra Olianas"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mastocytosis, a rare blood disorder characterized by the proliferation of clonal abnormal mast cells, has a variegated clinical spectrum and diagnosis is often difficult and delayed. Recently we proposed the cathepsin inhibitor cystatin D-R26 as a salivary candidate biomarker of systemic mastocytosis (SM). Its C26 variant is able to form multiprotein complexes (mPCs) and since protein\u2013protein interactions (PPIs) are crucial for studying disease pathogenesis, potential markers, and therapeutic targets, we aimed to define the protein composition of the salivary cystatin D-C26 interactome associated with SM. An exploratory affinity purification-mass spectrometry method was applied on pooled salivary samples from SM patients, SM patient subgroups with and without cutaneous symptoms (SM+C and SM\u2212C), and healthy controls (Ctrls). Interactors specifically detected in Ctrls were found to be implicated in networks associated with cell and tissue homeostasis, innate system, endopeptidase regulation, and antimicrobial protection. Interactors distinctive of SM\u2212C patients participate to PPI networks related to glucose metabolism, protein S-nitrosylation, antibacterial humoral response, and neutrophil degranulation, while interactors specific to SM+C were mainly associated with epithelial and keratinocyte differentiation, cytoskeleton rearrangement, and immune response pathways. Proteins sensitive to redox changes, as well as proteins with immunomodulatory properties and activating mast cells, were identified in patients; many of them were involved directly in cytoskeleton rearrangement, a process crucial for mast cell activation. Although preliminary, these results demonstrate that PPI alterations of the cystatin D-C26 interactome are associated with SM and provide a basis for future investigations based on quantitative proteomic analysis and immune validation.<\/jats:p>","DOI":"10.3390\/ijms241914613","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T03:49:14Z","timestamp":1695786554000},"page":"14613","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Salivary Cystatin D Interactome in Patients with Systemic Mastocytosis: An Exploratory Study"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1881-856X","authenticated-orcid":false,"given":"Simone","family":"Serrao","sequence":"first","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0903-4675","authenticated-orcid":false,"given":"Cristina","family":"Contini","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0448-276X","authenticated-orcid":false,"given":"Giulia","family":"Guadalupi","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Olianas","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greca","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1436-6105","authenticated-orcid":false,"given":"Irene","family":"Messana","sequence":"additional","affiliation":[{"name":"Istituto di Scienze e Tecnologie Chimiche \u201cGiulio Natta\u201d, Consiglio Nazionale delle Ricerche, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0959-7259","authenticated-orcid":false,"given":"Massimo","family":"Castagnola","sequence":"additional","affiliation":[{"name":"Proteomics Laboratory, European Center for Brain Research, (IRCCS) Santa Lucia Foundation, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2269-0439","authenticated-orcid":false,"given":"Giulia","family":"Costanzo","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5768-391X","authenticated-orcid":false,"given":"Davide","family":"Firinu","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Del Giacco","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2880-9915","authenticated-orcid":false,"given":"Barbara","family":"Manconi","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7535-9825","authenticated-orcid":false,"given":"Tiziana","family":"Cabras","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Valent, P., Akin, C., Gleixner, K.V., Sperr, W.R., Reiter, A., Arock, M., and Triggiani, M. 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