{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T18:15:43Z","timestamp":1777486543319,"version":"3.51.4"},"reference-count":103,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Amicus Therapeutics","award":["MRC_180321"],"award-info":[{"award-number":["MRC_180321"]}]},{"name":"Amicus Therapeutics","award":["UIDB\/50026\/2020 (DOI 10.54499\/UIDB\/50026\/2020)"],"award-info":[{"award-number":["UIDB\/50026\/2020 (DOI 10.54499\/UIDB\/50026\/2020)"]}]},{"name":"Amicus Therapeutics","award":["UIDP\/50026\/2020 (DOI 10.54499\/UIDP\/50026\/2020)"],"award-info":[{"award-number":["UIDP\/50026\/2020 (DOI 10.54499\/UIDP\/50026\/2020)"]}]},{"name":"Amicus Therapeutics","award":["LA\/P\/0050\/2020 (DOI 10.54499\/LA\/P\/0050\/2020)"],"award-info":[{"award-number":["LA\/P\/0050\/2020 (DOI 10.54499\/LA\/P\/0050\/2020)"]}]},{"name":"national funds","award":["MRC_180321"],"award-info":[{"award-number":["MRC_180321"]}]},{"name":"national funds","award":["UIDB\/50026\/2020 (DOI 10.54499\/UIDB\/50026\/2020)"],"award-info":[{"award-number":["UIDB\/50026\/2020 (DOI 10.54499\/UIDB\/50026\/2020)"]}]},{"name":"national funds","award":["UIDP\/50026\/2020 (DOI 10.54499\/UIDP\/50026\/2020)"],"award-info":[{"award-number":["UIDP\/50026\/2020 (DOI 10.54499\/UIDP\/50026\/2020)"]}]},{"name":"national funds","award":["LA\/P\/0050\/2020 (DOI 10.54499\/LA\/P\/0050\/2020)"],"award-info":[{"award-number":["LA\/P\/0050\/2020 (DOI 10.54499\/LA\/P\/0050\/2020)"]}]},{"name":"Component C5\u2014Capitalisation and Business Innovation","award":["MRC_180321"],"award-info":[{"award-number":["MRC_180321"]}]},{"name":"Component C5\u2014Capitalisation and Business Innovation","award":["UIDB\/50026\/2020 (DOI 10.54499\/UIDB\/50026\/2020)"],"award-info":[{"award-number":["UIDB\/50026\/2020 (DOI 10.54499\/UIDB\/50026\/2020)"]}]},{"name":"Component C5\u2014Capitalisation and Business Innovation","award":["UIDP\/50026\/2020 (DOI 10.54499\/UIDP\/50026\/2020)"],"award-info":[{"award-number":["UIDP\/50026\/2020 (DOI 10.54499\/UIDP\/50026\/2020)"]}]},{"name":"Component C5\u2014Capitalisation and Business Innovation","award":["LA\/P\/0050\/2020 (DOI 10.54499\/LA\/P\/0050\/2020)"],"award-info":[{"award-number":["LA\/P\/0050\/2020 (DOI 10.54499\/LA\/P\/0050\/2020)"]}]},{"name":"Foundation for Science and Technology (FCT)\u2014project","award":["MRC_180321"],"award-info":[{"award-number":["MRC_180321"]}]},{"name":"Foundation for Science and Technology (FCT)\u2014project","award":["UIDB\/50026\/2020 (DOI 10.54499\/UIDB\/50026\/2020)"],"award-info":[{"award-number":["UIDB\/50026\/2020 (DOI 10.54499\/UIDB\/50026\/2020)"]}]},{"name":"Foundation for Science and Technology (FCT)\u2014project","award":["UIDP\/50026\/2020 (DOI 10.54499\/UIDP\/50026\/2020)"],"award-info":[{"award-number":["UIDP\/50026\/2020 (DOI 10.54499\/UIDP\/50026\/2020)"]}]},{"name":"Foundation for Science and Technology (FCT)\u2014project","award":["LA\/P\/0050\/2020 (DOI 10.54499\/LA\/P\/0050\/2020)"],"award-info":[{"award-number":["LA\/P\/0050\/2020 (DOI 10.54499\/LA\/P\/0050\/2020)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Fabry Disease (FD) is one of the most prevalent lysosomal storage disorders, resulting from mutations in the GLA gene located on the X chromosome. This genetic mutation triggers glo-botriaosylceramide (Gb-3) buildup within lysosomes, ultimately impairing cellular functions. Given the role of lysosomes in immune cell physiology, FD has been suggested to have a profound impact on immunological responses. During the past years, research has been focusing on this topic, and pooled evidence strengthens the hypothesis that Gb-3 accumulation potentiates the production of pro-inflammatory mediators, revealing the existence of an acute inflammatory process in FD that possibly develops to a chronic state due to stimulus persistency. In parallel, extracellular vesicles (EVs) have gained attention due to their function as intercellular communicators. Considering EVs\u2019 capacity to convey cargo from parent to distant cells, they emerge as potential inflammatory intermediaries capable of transporting cytokines and other immunomodulatory molecules. In this review, we revisit the evidence underlying the association between FD and altered immune responses and explore the potential of EVs to function as inflammatory vehicles.<\/jats:p>","DOI":"10.3390\/cells13080654","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T02:52:17Z","timestamp":1712631137000},"page":"654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Inflammation and Exosomes in Fabry Disease Pathogenesis"],"prefix":"10.3390","volume":"13","author":[{"given":"Bruna","family":"Coelho-Ribeiro","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga\/4805-017 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9183-6561","authenticated-orcid":false,"given":"Helena G.","family":"Silva","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga\/4805-017 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6580-0971","authenticated-orcid":false,"given":"Bel\u00e9m","family":"Sampaio-Marques","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga\/4805-017 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-1629","authenticated-orcid":false,"given":"Alexandra G.","family":"Fraga","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga\/4805-017 Guimar\u00e3es, Portugal"}]},{"given":"Olga","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Reference Center on Lysosomal Storage Disorders, Hospital Senhora da Oliveira, 4835-044 Guimar\u00e3es, Portugal"}]},{"given":"Jorge","family":"Pedrosa","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga\/4805-017 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4130-7167","authenticated-orcid":false,"given":"Paula","family":"Ludovico","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga\/4805-017 Guimar\u00e3es, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ymgme.2017.09.004","article-title":"Contribution of inflammatory pathways to Fabry disease pathogenesis","volume":"122","author":"Rozenfeld","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"jcs221739","DOI":"10.1242\/jcs.221739","article-title":"Lysosomal storage disorders-challenges, concepts and avenues for therapy: Beyond rare diseases","volume":"132","author":"Marques","year":"2019","journal-title":"J. Cell Sci."},{"key":"ref_3","unstructured":"Rajkumar, V., and Dumpa, V. (2022). StatPearls, StatPearls Publishing."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/B978-0-444-62702-5.00017-2","article-title":"Fabry disease","volume":"132","author":"Schiffmann","year":"2015","journal-title":"Handb. Clin. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jpeds.2014.09.023","article-title":"Lysosomal storage disorder screening implementation: Findings from the first six months of full population pilot testing in Missouri","volume":"166","author":"Hopkins","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.ymgme.2016.05.015","article-title":"Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry","volume":"118","author":"Elliott","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jpeds.2017.06.048","article-title":"Newborn Screening for Lysosomal Storage Disorders in Illinois: The Initial 15-Month Experience","volume":"190","author":"Burton","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/s41436-018-0129-y","article-title":"The New York pilot newborn screening program for lysosomal storage diseases: Report of the First 65,000 Infants","volume":"21","author":"Wasserstein","year":"2019","journal-title":"Genet. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100562","DOI":"10.1016\/j.ymgmr.2019.100562","article-title":"Newborn screening for Fabry disease in the western region of Japan","volume":"22","author":"Sawada","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.amjms.2020.07.011","article-title":"When and How to Diagnose Fabry Disease in Clinical Pratice","volume":"360","author":"Michaud","year":"2020","journal-title":"Am. J. Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kok, K., Zwiers, K.C., Boot, R.G., Overkleeft, H.S., Aerts, J., and Artola, M. (2021). Fabry Disease: Molecular Basis, Pathophysiology, Diagnostics and Potential Therapeutic Directions. Biomolecules, 11.","DOI":"10.3390\/biom11020271"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Simonetta, I., Tuttolomondo, A., Daidone, M., and Pinto, A. (2020). Biomarkers in Anderson-Fabry Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218080"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rocchetti, M.T., Spadaccino, F., Catalano, V., Zaza, G., Stallone, G., Fiocco, D., Netti, G.S., and Ranieri, E. (2022). Metabolic Fingerprinting of Fabry Disease: Diagnostic and Prognostic Aspects. Metabolites, 12.","DOI":"10.3390\/metabo12080703"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Capelli, I., Aiello, V., Gasperoni, L., Comai, G., Corradetti, V., Ravaioli, M., Biagini, E., Graziano, C., and La Manna, G. (2020). Kidney Transplant in Fabry Disease: A Revision of the Literature. Medicina, 56.","DOI":"10.3390\/medicina56060284"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Azevedo, O., Gago, M.F., Miltenberger-Miltenyi, G., Sousa, N., and Cunha, D. (2020). Fabry Disease Therapy: State-of-the-Art and Current Challenges. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010206"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Azevedo, O., Cordeiro, F., Gago, M.F., Miltenberger-Miltenyi, G., Ferreira, C., Sousa, N., and Cunha, D. (2021). Fabry Disease and the Heart: A Comprehensive Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094434"},{"key":"ref_17","first-page":"e160025","article-title":"Anderson-Fabry Disease: A Rare Disease That Mimics Common Cardiac, Neurological, Renal, and Other Disorders: Approach for the Differential Diagnosis and Follow-Up","volume":"4","author":"Cabrita","year":"2016","journal-title":"Sage J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ivanova, M.M., Changsila, E., Iaonou, C., and Goker-Alpan, O. (2019). Impaired autophagic and mitochondrial functions are partially restored by ERT in Gaucher and Fabry diseases. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0210617"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s10545-010-9114-6","article-title":"A modified lipid composition in Fabry disease leads to an intracellular block of the detergent-resistant membrane-associated dipeptidyl peptidase IV","volume":"33","author":"Maalouf","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hassanpour, M., Rezabakhsh, A., Rezaie, J., Nouri, M., and Rahbarghazi, R. (2020). Exosomal cargos modulate autophagy in recipient cells via different signaling pathways. Cell Biosci., 10.","DOI":"10.1186\/s13578-020-00455-7"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3390\/cells2010083","article-title":"Divergent roles of autophagy in virus infection","volume":"2","author":"Chiramel","year":"2013","journal-title":"Cells"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"589","DOI":"10.4161\/auto.6.5.11943","article-title":"Autophagosome maturation is impaired in Fabry disease","volume":"6","author":"Chevrier","year":"2010","journal-title":"Autophagy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1186\/s13023-022-02441-3","article-title":"Autophagy-lysosome pathway alteration in ocular surface manifestations in Fabry disease patients","volume":"17","author":"Marenco","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/2051-5960-2-20","article-title":"Autophagy-lysosome pathway associated neuropathology and axonal degeneration in the brains of alpha-galactosidase A-deficient mice","volume":"2","author":"Nelson","year":"2014","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"208","DOI":"10.23876\/j.krcp.20.264","article-title":"Fabry disease exacerbates renal interstitial fibrosis after unilateral ureteral obstruction via impaired autophagy and enhanced apoptosis","volume":"40","author":"Chung","year":"2021","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0168-9525(03)00081-7","article-title":"Hypertrophic cardiomyopathy:a paradigm for myocardial energy depletion","volume":"19","author":"Ashrafian","year":"2003","journal-title":"Trends Genet. TIG"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1016\/j.humpath.2015.07.017","article-title":"Increased oxidative stress contributes to cardiomyocyte dysfunction and death in patients with Fabry disease cardiomyopathy","volume":"46","author":"Chimenti","year":"2015","journal-title":"Hum. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.ymgme.2011.06.007","article-title":"Higher apoptotic state in Fabry disease peripheral blood mononuclear cells.: Effect of globotriaosylceramide","volume":"104","author":"Mucci","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ivanova, M. (2020). Altered Sphingolipids Metabolism Damaged Mitochondrial Functions: Lessons Learned from Gaucher and Fabry Diseases. J. Clin. Med., 9.","DOI":"10.3390\/jcm9041116"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"231","DOI":"10.4196\/kjpp.2023.27.3.231","article-title":"Lyso-globotriaosylsphingosine induces endothelial dysfunction via autophagy-dependent regulation of necroptosis","volume":"27","author":"Hwang","year":"2023","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1111\/j.1440-1681.2008.04984.x","article-title":"Vascular dysfunction in the alpha-galactosidase A-knockout mouse is an endothelial cell-, plasma membrane-based defect","volume":"35","author":"Park","year":"2008","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"G140","DOI":"10.1152\/ajpgi.00185.2013","article-title":"Endothelial nitric oxide synthase uncoupling and microvascular dysfunction in the mesentery of mice deficient in alpha-galactosidase A","volume":"306","author":"Kang","year":"2014","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ymgme.2022.10.005","article-title":"Clinical relevance of globotriaosylceramide accumulation in Fabry disease and the effect of agalsidase beta in affected tissues","volume":"137","author":"Tondel","year":"2022","journal-title":"Mol. Genet. Metab."},{"key":"ref_34","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."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Namdar, M., Gebhard, C., Studiger, R., Shi, Y., Mocharla, P., Schmied, C., Brugada, P., Luscher, T.F., and Camici, G.G. (2012). Globotriaosylsphingosine accumulation and not alpha-galactosidase-A deficiency causes endothelial dysfunction in Fabry disease. PLoS ONE, 7.","DOI":"10.1371\/annotation\/7b2c04df-8592-4fb7-8608-3039db28b504"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1161\/STROKEAHA.114.006283","article-title":"Cerebrovascular involvement in Fabry disease: Current status of knowledge","volume":"46","author":"Kolodny","year":"2015","journal-title":"Stroke"},{"key":"ref_37","first-page":"5548445","article-title":"Anderson-Fabry Disease: From Endothelial Dysfunction to Emerging Therapies","volume":"2021","author":"Stamerra","year":"2021","journal-title":"Adv. Pharmacol. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/ki.2013.520","article-title":"Establishing 3-nitrotyrosine as a biomarker for the vasculopathy of Fabry disease","volume":"86","author":"Shu","year":"2014","journal-title":"Kidney Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6009","DOI":"10.2174\/13816128113199990347","article-title":"Gastroenterological complications of Anderson-Fabry disease","volume":"19","author":"Buda","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1159\/000521329","article-title":"Growth Differentiation Factor-15 and Syndecan-1 Are Potential Biomarkers of Cardiac and Renal Involvement in Classical Fabry Disease under Enzyme Replacement Therapy","volume":"47","author":"Gregorio","year":"2022","journal-title":"Kidney Blood Press Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ymgme.2009.10.004","article-title":"Vasculopathy in patients with Fabry disease: Current controversies and research directions","volume":"99","author":"Rombach","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1134\/S0006297916110018","article-title":"Molecular and Cellular Mechanisms of Inflammation","volume":"81","author":"Kuprash","year":"2016","journal-title":"Biochem. Biokhimiia"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Mariani, E., Lisignoli, G., Borzi, R.M., and Pulsatelli, L. (2019). Biomaterials: Foreign Bodies or Tuners for the Immune Response?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030636"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.chom.2011.04.006","article-title":"Trained immunity: A memory for innate host defense","volume":"9","author":"Netea","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/454427a","article-title":"Inflammation","volume":"454","author":"Weiss","year":"2008","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s40292-020-00414-w","article-title":"The role of Immunity in Fabry Disease and Hypertension: A Review of a Novel Common Pathway","volume":"27","author":"Ferri","year":"2020","journal-title":"High Blood Press. Cardiovasc. Prev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.molmed.2019.01.006","article-title":"Is Resolution the End of Inflammation?","volume":"25","author":"Feehan","year":"2019","journal-title":"Trends Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/8904_2014_371","article-title":"Innate and Adaptive Immune Response in Fabry Disease","volume":"22","author":"Mauhin","year":"2015","journal-title":"JIMD Rep."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Carnicer-Caceres, C., Arranz-Amo, J.A., Cea-Arestin, C., Camprodon-Gomez, M., Moreno-Martinez, D., Lucas-Del-Pozo, S., Molto-Abad, M., Tigri-Santina, A., Agraz-Pamplona, I., and Rodriguez-Palomares, J.F. (2021). Biomarkers in Fabry Disease. Implications for Clinical Diagnosis and Follow-up. J. Clin. Med., 10.","DOI":"10.3390\/jcm10081664"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ymgme.2013.02.003","article-title":"Fabry disease peripheral blood immune cells release inflammatory cytokines: Role of globotriaosylceramide","volume":"109","author":"Mucci","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e2643","DOI":"10.6061\/clinics\/2021\/e2643","article-title":"Increased Serum Interleukin-6 and Tumor Necrosis Factor Alpha Levels in Fabry Disease: Correlation with Disease Burden","volume":"76","author":"Bento","year":"2021","journal-title":"Clinics"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Tebani, A., Mauhin, W., Abily-Donval, L., Lesueur, C., Berger, M.G., Nadjar, Y., Berger, J., Benveniste, O., Lamari, F., and Laforet, P. (2020). A Proteomics-Based Analysis Reveals Predictive Biological Patterns in Fabry Disease. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051325"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e009098","DOI":"10.1161\/JAHA.118.009098","article-title":"Elevated Inflammatory Plasma Biomarkers in Patients with Fabry Disease: A Critical Link to Heart Failure with Preserved Ejection Fraction","volume":"7","author":"Yogasundaram","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ymgme.2019.05.009","article-title":"Tumor necrosis factor-alpha links heat and inflammation with Fabry pain","volume":"127","author":"Uceyler","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"C130","DOI":"10.1093\/eurheartjsupp\/suad015","article-title":"Diagnostic and prognostic role of late gadolinium enhancement in cardiomyopathies","volume":"25","author":"Aquaro","year":"2023","journal-title":"Eur. Heart J. Suppl."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1007\/s10545-009-1060-9","article-title":"Leukocyte perturbation associated with Fabry disease","volume":"32","author":"Rozenfeld","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/nm1663","article-title":"TLR4 enhances TGF-beta signaling and hepatic fibrosis","volume":"13","author":"Seki","year":"2007","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.2337\/db08-0061","article-title":"3rd. From fibrosis to sclerosis: Mechanisms of glomerulosclerosis in diabetic nephropathy","volume":"57","author":"Qian","year":"2008","journal-title":"Diabetes"},{"key":"ref_60","first-page":"1683","article-title":"Altered immune phenotypes in subjects with Fabry disease and responses to switching from agalsidase alfa to agalsidase beta","volume":"11","author":"Limgala","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Spitzel, M., Wagner, E., Breyer, M., Henniger, D., Bayin, M., Hofmann, L., Mauceri, D., Sommer, C., and Uceyler, N. (2022). Dysregulation of Immune Response Mediators and Pain-Related Ion Channels Is Associated with Pain-like Behavior in the GLA KO Mouse Model of Fabry Disease. Cells, 11.","DOI":"10.3390\/cells11111730"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ymgme.2013.01.018","article-title":"Invariant natural killer T cells are phenotypically and functionally altered in Fabry disease","volume":"108","author":"Pereira","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.immuni.2010.08.003","article-title":"Lysosomal alpha-galactosidase controls the generation of self lipid antigens for natural killer T cells","volume":"33","author":"Darmoise","year":"2010","journal-title":"Immunity"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Abasolo, I., Seras-Franzoso, J., Molto-Abad, M., Diaz-Riascos, V., Corchero, J.L., Pintos-Morell, G., and Schwartz, S. (2021). Nanotechnology-based approaches for treating lysosomal storage disorders, a focus on Fabry disease. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 13.","DOI":"10.1002\/wnan.1684"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/gim.2018.31","article-title":"Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis","volume":"21","author":"Maruyama","year":"2019","journal-title":"Genet. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e00949","DOI":"10.1002\/prp2.949","article-title":"Inhibition of epigenetic reader proteins by apabetalone counters inflammation in activated innate immune cells from Fabry disease patients receiving enzyme replacement therapy","volume":"10","author":"Fu","year":"2022","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1307558","DOI":"10.3389\/fimmu.2024.1307558","article-title":"Complement activation and cellular inflammation in Fabry disease patients despite enzyme replacement therapy","volume":"15","author":"Laffer","year":"2024","journal-title":"Front. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1221.e1\u2013e9","DOI":"10.1016\/j.cjca.2015.10.033","article-title":"Evaluation of Proinflammatory Prognostic Biomarkers for Fabry Cardiomyopathy with Enzyme Replacement Therapy","volume":"32","author":"Chen","year":"2016","journal-title":"Can. J. Cardiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1750-1172-8-47","article-title":"Long term enzyme replacement therapy for Fabry disease: Effectiveness on kidney, heart and brain","volume":"8","author":"Rombach","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1750-1172-8-29","article-title":"Cost-effectiveness of enzyme replacement therapy for Fabry disease","volume":"8","author":"Rombach","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/jhg.2016.78","article-title":"Long-term enzyme replacement therapy for Fabry disease: Efficacy and unmet needs in cardiac and renal outcomes","volume":"61","author":"Kim","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"100454","DOI":"10.1016\/j.ymgmr.2019.100454","article-title":"The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts","volume":"19","author":"Germain","year":"2019","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1159\/000448968","article-title":"Long Term Treatment with Enzyme Replacement Therapy in Patients with Fabry Disease","volume":"134","author":"Oder","year":"2016","journal-title":"Nephron"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6","DOI":"10.5734\/JGM.2023.20.1.6","article-title":"Fabry disease: Current treatment and future perspective","volume":"20","author":"Yoo","year":"2023","journal-title":"J. Genet. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"100805","DOI":"10.1016\/j.gimo.2023.100805","article-title":"New Insights in Efficacy of Different ERT Dosages in Fabry Disease: Switch and Switch-Back Studies Data Following Agalsidase Beta Shortage. Update of Systematic Review","volume":"1","author":"Capuano","year":"2023","journal-title":"Genet. Med. Open"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Maria Dolores Sanchez-Ni\u00f1o, A.O. (2016). Enzyme Replacement Therapy for Fabry Disease. J. Inborn Errors Metab. Screen., 4.","DOI":"10.1177\/2326409816679428"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s10571-016-0366-z","article-title":"Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake","volume":"36","author":"Abels","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.3389\/fimmu.2020.01040","article-title":"Modulating Cytokine Production via Select Packaging and Secretion from Extracellular Vesicles","volume":"11","author":"Barnes","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Sun, Y.Z., Ruan, J.S., Jiang, Z.S., Wang, L., and Wang, S.M. (2018). Extracellular Vesicles: A New Perspective in Tumor Therapy. BioMed Res. Int., 2018.","DOI":"10.1155\/2018\/2687954"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Song, H.Y., Chien, C.S., Yarmishyn, A.A., Chou, S.J., Yang, Y.P., Wang, M.L., Wang, C.Y., Leu, H.B., Yu, W.C., and Chang, Y.L. (2019). Generation of GLA-Knockout Human Embryonic Stem Cell Lines to Model Autophagic Dysfunction and Exosome Secretion in Fabry Disease-Associated Hypertrophic Cardiomyopathy. Cells, 8.","DOI":"10.3390\/cells8040327"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Doyle, L.M., and Wang, M.Z. (2019). Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 8.","DOI":"10.3390\/cells8070727"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2174\/1570159X14666160825160421","article-title":"Exosomes: The Messengers of Health and Disease","volume":"15","author":"Isola","year":"2017","journal-title":"Curr. Neuropharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/j.jprot.2010.06.006","article-title":"Exosomes: Extracellular organelles important in intercellular communication","volume":"73","author":"Mathivanan","year":"2010","journal-title":"J. Proteom."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Simeone, P., Bologna, G., Lanuti, P., Pierdomenico, L., Guagnano, M.T., Pieragostino, D., Del Boccio, P., Vergara, D., Marchisio, M., and Miscia, S. (2020). Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072514"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"386","DOI":"10.7555\/JBR.30.20150162","article-title":"Exosomes and their role in the micro-\/macro-environment: A comprehensive review","volume":"31","author":"Javeed","year":"2017","journal-title":"J. Biomed. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.7150\/thno.52570","article-title":"Engineering exosomes for targeted drug delivery","volume":"11","author":"Liang","year":"2021","journal-title":"Theranostics"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1143905","DOI":"10.3389\/fmed.2023.1143905","article-title":"Urinary-derived extracellular vesicles reveal a distinct microRNA signature associated with the development and progression of Fabry nephropathy","volume":"10","author":"Levstek","year":"2023","journal-title":"Front. Med."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Lo Curto, A., Taverna, S., Costa, M.A., Passantino, R., Augello, G., Adamo, G., Aiello, A., Colomba, P., Zizzo, C., and Zora, M. (2021). Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease. Cells, 10.","DOI":"10.3390\/cells10020356"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"567","DOI":"10.21873\/invivo.13475","article-title":"Exosome Secretion and Cellular Signaling Change in a Fabry Disease Cell Model Induced by Gene-silencing","volume":"38","author":"Park","year":"2024","journal-title":"In Vivo"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.ccell.2016.10.009","article-title":"Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis","volume":"30","author":"Becker","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"657086","DOI":"10.1155\/2015\/657086","article-title":"Exosomes: Novel biomarkers for clinical diagnosis","volume":"2015","author":"Lin","year":"2015","journal-title":"Sci. World J."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1038\/emboj.2011.286","article-title":"Endosome maturation","volume":"30","author":"Huotari","year":"2011","journal-title":"EMBO J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"638111","DOI":"10.3389\/fimmu.2021.638111","article-title":"Co-Isolation of Cytokines and Exosomes: Implications for Immunomodulation Studies","volume":"12","author":"Koroleva","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"8973","DOI":"10.1038\/s41598-018-27190-x","article-title":"A System of Cytokines Encapsulated in ExtraCellular Vesicles","volume":"8","author":"Fitzgerald","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1186\/s12967-020-02560-0","article-title":"Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis\/chronic fatigue syndrome: A pilot study","volume":"18","author":"Giloteaux","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Hezel, M.E.V., Nieuwland, R., Bruggen, R.V., and Juffermans, N.P. (2017). The Ability of Extracellular Vesicles to Induce a Pro-Inflammatory Host Response. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061285"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrc1098","article-title":"The pathogenesis of cancer metastasis: The \u2018seed and soil\u2019 hypothesis revisited","volume":"3","author":"Fidler","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/ncb3169","article-title":"Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver","volume":"17","author":"Aiello","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1002\/ijc.23925","article-title":"Stromal myofibroblasts are drivers of invasive cancer growth","volume":"123","author":"Demetter","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.4049\/jimmunol.176.3.1375","article-title":"Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function","volume":"176","author":"Liu","year":"2006","journal-title":"J. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ymgme.2019.11.010","article-title":"Extracellular vesicles increase the enzymatic activity of lysosomal proteins and improve the efficacy of enzyme replacement therapy in Fabry disease","volume":"129","author":"Abasolo","year":"2020","journal-title":"Mol. Genet. Metab."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e12058","DOI":"10.1002\/jev2.12058","article-title":"Extracellular vesicles from recombinant cell factories improve the activity and efficacy of enzymes defective in lysosomal storage disorders","volume":"10","author":"Corchero","year":"2021","journal-title":"J. Extracell. 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