{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:53:08Z","timestamp":1790679188336,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2013,1,18]],"date-time":"2013-01-18T00:00:00Z","timestamp":1358467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,1,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fabry disease (FD) is an X-linked progressive multisystem disease due to mutations in the gene encoding the lysosomal enzyme \u03b1-galactosidase A (\u03b1-GalA). The deficiency in \u03b1-GalA activity leads to an intra-lysosomal accumulation of neutral glycosphingolipids, mainly globotriaosylceramide (Gb3), in various organs and systems. Enzyme replacement therapy is available and alternative therapeutic approaches are being explored. No diagnostic test, other than sequencing of the \u03b1-galactosidase A gene, is available, no biomarker has been proven useful to screen for and predict the disease, and underlying mechanisms are still elusive. The aim of this study is to identify FD specific biomarkers and to better understand the pathophysiological changes that occur over time in FD. We compared peripheral blood mononuclear cells (PBMC) from FD patients (n = 8) with control PBMC from healthy individuals (n = 6), by two-dimensional electrophoresis (2DE) and the detected differentially expressed proteins were then subjected to matrix-assisted laser desorption\/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). In FD patients we identified, among the down-regulated proteins, Calnexin, Rho GDP-dissociation inhibitor 2, Rho GDP-dissociation inhibitor 1, Chloride intracellular channel protein 1; on the other hand \u03b3-enolase, 14-3-3 protein theta, 14-3-3 protein zeta\/delta, and galectin-1 were identified as up-regulated proteins. Calnexin and Rho GDP-dissociation inhibitor-1,2 are related to protein folding, signal transduction and cell proliferation. This is the first time that \u03b3-enolase and galectin-1 are described to be up-regulated in Fabry patients. Levels of \u03b3-enolase increase dramatically in cardiovascular accidents and cerebral trauma, whereas galectins are regulators of acute and chronic inflammation. These findings may improve our understanding of the molecular mechanisms underlying the pathology and provide new insight and knowledge for future studies in this field.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/c3mb25402j","type":"journal-article","created":{"date-parts":[[2013,1,18]],"date-time":"2013-01-18T08:34:44Z","timestamp":1358498084000},"page":"1162-1168","source":"Crossref","is-referenced-by-count":34,"title":["Alteration of proteomic profiles in PBMC isolated from patients with Fabry disease: preliminary findings"],"prefix":"10.1093","volume":"9","author":[{"given":"Diego","family":"Cigna","sequence":"first","affiliation":[{"name":"Laboratory of Proteomics, Institute of Biomedicine and Molecular Immunology (IBIM), CNR a , Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"D'Anna","sequence":"additional","affiliation":[{"name":"Laboratory of Proteomics, Institute of Biomedicine and Molecular Immunology (IBIM), CNR a , Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Zizzo","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology Applied to Medical Sciences, Institute of Biomedicine and Molecular Immunology (IBIM), CNR b , Palermo, Italy \u00a0 duro@ibim.cnr.it"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Francofonte","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology Applied to Medical Sciences, Institute of Biomedicine and Molecular Immunology (IBIM), CNR b , Palermo, Italy \u00a0 duro@ibim.cnr.it"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iacopo","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology Applied to Medical Sciences, Institute of Biomedicine and Molecular Immunology (IBIM), CNR b , Palermo, Italy \u00a0 duro@ibim.cnr.it"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Colomba","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology Applied to Medical Sciences, Institute of Biomedicine and Molecular Immunology (IBIM), CNR b , Palermo, Italy \u00a0 duro@ibim.cnr.it"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Albeggiani","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology Applied to Medical Sciences, Institute of Biomedicine and Molecular Immunology (IBIM), CNR b , Palermo, Italy \u00a0 duro@ibim.cnr.it"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Armini","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Proteomics, Molecular Biology Department, Universit\u00e0 degli Studi di Siena c , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Proteomics, Molecular Biology Department, Universit\u00e0 degli Studi di Siena c , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Bini","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Proteomics, Molecular Biology Department, Universit\u00e0 degli Studi di Siena c , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Duro","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology Applied to Medical Sciences, Institute of Biomedicine and Molecular Immunology (IBIM), CNR b , Palermo, Italy \u00a0 duro@ibim.cnr.it"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,1,18]]},"reference":[{"key":"2026012913094260800_cit1","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1056\/NEJM196705252762101","article-title":"Enzymatic defect in Fabry's disease, Ceramidetrihexosidase deficiency","volume":"276","author":"Brady","year":"1967","journal-title":"N. Engl. J. Med."},{"key":"2026012913094260800_cit2","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1126\/science.167.3922.1268","article-title":"Fabry's disease: alpha-galactosidase deficiency","volume":"167","author":"Kint","year":"1970","journal-title":"Science"},{"key":"2026012913094260800_cit3","first-page":"pp. 3733\u20133774","article-title":"\u03b1-galactosidase A deficiency: Fabry disease","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Desnick","year":"2000"},{"key":"2026012913094260800_cit4","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1203\/PDR.0b013e318183f132","article-title":"Characterization of Fabry disease in 352 pediatric patients in the Fabry Registry","volume":"64","author":"Hopkin","year":"2008","journal-title":"Pediatr. Res."},{"key":"2026012913094260800_cit5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1651-2227.2006.tb02186.x","article-title":"Clinical manifestations of Fabry disease in children: data from the Fabry Outcome Survey","volume":"95","author":"Ramaswami","year":"2006","journal-title":"Acta Paediatr."},{"key":"2026012913094260800_cit6","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/S0140-6736(08)61589-5","article-title":"Fabry's disease","volume":"372","author":"Zarate","year":"2008","journal-title":"Lancet"},{"key":"2026012913094260800_cit7","volume-title":"Alpha-galactosidase A deficiency: Fabry disease","author":"Desnick","year":"2001"},{"key":"2026012913094260800_cit8","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1042\/BJ20070479","article-title":"Mutant alpha-galactosidase A enzymes identified in Fabry disease patients with residual enzyme activity: biochemical characterization and restoration of normal intracellular processing by 1-deoxygalactonojirimycin","volume":"406","author":"Ishii","year":"2007","journal-title":"Biochem. J."},{"key":"2026012913094260800_cit9","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1006\/abbi.2000.1743","article-title":"Role of Ser-65 in the activity of alpha-galactosidase A: characterization of a point mutation (S65T) detected in a patient with Fabry disease","volume":"377","author":"Ishii","year":"2000","journal-title":"Arch. Biochem. Biophys."},{"key":"2026012913094260800_cit10","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1006\/bbrc.1993.2659","article-title":"Characterization of a mutant alpha-galactosidase gene product for the late-onset cardiac form of Fabry disease","volume":"197","author":"Ishii","year":"1993","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026012913094260800_cit11","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ymgme.2008.06.016","article-title":"Globotriaosylceramide induces oxidative stress and up-regulates cell adhesion molecule expression in Fabry disease endothelial cells","volume":"95","author":"Shen","year":"2008","journal-title":"Mol. Genet. Metab."},{"issue":"suppl. 1","key":"2026012913094260800_cit12","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s10545-009-1060-9","article-title":"Leukocyte perturbation associated with Fabry disease","volume":"32","author":"Rozenfeld","year":"2009","journal-title":"J. Inherited Metab. Dis."},{"key":"2026012913094260800_cit13","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ymgme.2008.06.016","article-title":"Globotriaosylceramide induces oxidative stress and up-regulates cell adhesion molecule expression in Fabry disease endothelial cells","volume":"95","author":"Shen","year":"2008","journal-title":"Mol. 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Int."},{"key":"2026012913094260800_cit19","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.4049\/jimmunol.160.10.4831","article-title":"Activated rat macrophages produce a galectin-1-like protein that induces apoptosis of T cells: biochemical and functional characterization","volume":"160","author":"Rabinovich","year":"1998","journal-title":"J. Immunol."},{"key":"2026012913094260800_cit20","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1002\/(SICI)1521-4141(199808)28:08<2311::AID-IMMU2311>3.0.CO;2-G","article-title":"Beta-galactoside-binding protein secreted by activated T cells inhibits antigen-induced proliferation of T cells","volume":"28","author":"Blaser","year":"1998","journal-title":"Eur. J. 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