{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:12:50Z","timestamp":1760238770498,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,5]],"date-time":"2020-09-05T00:00:00Z","timestamp":1599264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF\/2009 1471624"],"award-info":[{"award-number":["RF\/2009 1471624"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic antibody-mediated rejection (CAMR) is the major cause of kidney transplant failure. The molecular mechanisms underlying this event are still poorly defined and this lack of knowledge deeply influences the potential therapeutic strategies. The aim of our study was to analyze the phosphoproteome of peripheral blood mononuclear cells (PBMCs), to identify cellular signaling networks differentially activated in CAMR. Phosphoproteins isolated from PBMCs of biopsy proven CAMR, kidney transplant recipients with normal graft function and histology and healthy immunocompetent individuals, have been investigated by proteomic analysis. Phosphoproteomic results were confirmed by Western blot and PBMCs\u2019 confocal microscopy analyses. Overall, 38 PBMCs samples were analyzed. A differential analysis of PBMCs\u2019 phosphoproteomes revealed an increase of lactotransferrin, actin-related protein 2 (ARPC2) and calgranulin-B in antibody-mediated rejection patients, compared to controls. Increased expression of phosphorylated ARPC2 and its correlation to F-actin filaments were confirmed in CAMR patients. Our results are the first evidence of altered cytoskeleton organization in circulating immune cells of CAMR patients. The increased expression of phosphorylated ARPC2 found in the PBMCs of our patients, and its association with derangement of F-actin filaments, might suggest that proteins regulating actin dynamics in immune cells could be involved in the mechanism of CAMR of kidney grafts.<\/jats:p>","DOI":"10.3390\/ijms21186509","type":"journal-article","created":{"date-parts":[[2020,9,6]],"date-time":"2020-09-06T23:12:49Z","timestamp":1599433969000},"page":"6509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Altered Phosphorylation of Cytoskeleton Proteins in Peripheral Blood Mononuclear Cells Characterizes Chronic Antibody-Mediated Rejection in Kidney Transplantation"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2397-6474","authenticated-orcid":false,"given":"Maria Teresa","family":"Rocchetti","sequence":"first","affiliation":[{"name":"Clinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, Faculty of Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Rascio","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, Faculty of Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Castellano","sequence":"additional","affiliation":[{"name":"Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, Faculty of Medicine University of Foggia, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7334-8372","authenticated-orcid":false,"given":"Marco","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Nephrology Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, Faculty of Medicine, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3495-2707","authenticated-orcid":false,"given":"Giuseppe Stefano","family":"Netti","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, Faculty of Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4375-0560","authenticated-orcid":false,"given":"Federica","family":"Spadaccino","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, Faculty of Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4996-3938","authenticated-orcid":false,"given":"Elena","family":"Ranieri","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, Faculty of Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Gallone","sequence":"additional","affiliation":[{"name":"Experimental Biology, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Faculty of Medicine, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loreto","family":"Gesualdo","sequence":"additional","affiliation":[{"name":"Nephrology Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, Faculty of Medicine, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Stallone","sequence":"additional","affiliation":[{"name":"Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, Faculty of Medicine University of Foggia, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7654-8318","authenticated-orcid":false,"given":"Paola","family":"Pontrelli","sequence":"additional","affiliation":[{"name":"Experimental Biology, Department of Emergency and Organ Transplantation, Faculty of Medicine, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Grandaliano","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Faculty of Medicine, Catholic University of the Sacred Heart, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/j.1600-6143.2011.03840.x","article-title":"Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody-Mediated Rejection and Nonadherence","volume":"12","author":"Mengel","year":"2012","journal-title":"Am. J. Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1111\/j.1600-6143.2009.02799.x","article-title":"Antibody-Mediated Microcirculation Injury Is the Major Cause of Late Kidney Transplant Failure","volume":"9","author":"Einecke","year":"2009","journal-title":"Am. J. 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