{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T08:13:13Z","timestamp":1777882393165,"version":"3.51.4"},"reference-count":41,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Rare Disease"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Fabry disease is a multisystemic lysosomal disorder caused by mutations in the GLA gene. Although traditionally attributed to lysosomal accumulation of globotriaosylceramide (Gb3), recent evidence suggests a key role of sustained systemic inflammation in its pathogenesis, even in early stages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To characterize inflammatory and immunological profiles in a genetically stratified familial cohort with Fabry disease and explore genotype-dependent immune activation patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Retrospective, longitudinal study of 11 patients from three interconnected families carrying distinct pathogenic GLA variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We analyzed longitudinal data on inflammatory biomarkers (C-reactive protein, ferritin, fibrinogen) and immunological markers (IgG, IgM, IgE, complement C3\/C4, anti-enzyme replacement therapy antibodies), alongside clinical variables. Multivariate correlation and unsupervised clustering techniques explored immunophenotypic patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>All patients exhibited chronic inflammation regardless of genotype. The c.53dup variant showed prominent humoral activation, IVS4+1G&gt;A had complement-mediated activation with a cardiorenal phenotype, and c.845C&gt;T showed mild persistent inflammation. Correlations included CRP and IgG, and complement factors with fibrinogen in the splicing variant group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Inflammation in Fabry disease is not merely a consequence of substrate accumulation but an active and early driver of disease. Preliminary inflammatory phenotypes based on immune mechanisms may guide future personalized therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/26330040251375498","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T08:18:36Z","timestamp":1757578716000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Systemic inflammation in Fabry disease: a longitudinal immuno-genetic analysis based on variant stratification"],"prefix":"10.1177","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1450-4384","authenticated-orcid":false,"given":"Haylen","family":"Mar\u00edn G\u00f3mez","sequence":"first","affiliation":[{"name":"Internal Medicine, Hospital Universitario San Agust\u00edn de Linares, \u00c1rea de Gesti\u00f3n Sanitaria Norte de Ja\u00e9n \u2013 Servicio Andaluz de Salud (SSPA), Avenida San Crist\u00f3bal s\/n, Linares, Ja\u00e9n 23700, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6566-3345","authenticated-orcid":false,"given":"Miguel","family":"L\u00f3pez-Garrido","sequence":"additional","affiliation":[{"name":"Cardiology, Hospital Universitario San Agust\u00edn de Linares, \u00c1rea de Gesti\u00f3n Sanitaria Norte de Ja\u00e9n \u2013 Servicio Andaluz de Salud (SSPA), Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-30"},{"key":"e_1_3_4_3_2","volume-title":"The metabolic and molecular bases of inherited disease","author":"Desnick RJ","year":"2001","unstructured":"Desnick RJ, Ioannou YA, Eng CM. Alpha-Galactosidase A deficiency: Fabry disease. In: Valle D, Beaudet AL, Vogelstein B, et al., editors. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001.","edition":"8"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712309105"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61589-5"},{"issue":"9","key":"e_1_3_4_6_2","article-title":"Cardiac and vascular hypertrophy in Fabry disease: Evidence for a new mechanism","volume":"5","author":"Barbey F","year":"2010","unstructured":"Barbey F, Brakch N, Linhart A, et al. Cardiac and vascular hypertrophy in Fabry disease: Evidence for a new mechanism. 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