López Valverde, LauraVázquez Mosquera, María EugeniaColón Mejeras, CristóbalBravo López, Susana BelénBarbosa Gouveia, SofiaÁlvarez González, José VíctorSánchez Martínez, RosarioLópez Mendoza, ManuelLópez Rodríguez, MónicaVillacorta Argüelles, EduardoGoicoechea Diezhandino, María A.Guerrero Márquez, Francisco J.Ortolano, SaidaLeao Teles, ElisaHermida Ameijeiras, ÁlvaroCouce Pico, María Luz2024-05-202024-05-202024Translational Research, Volume 269, 2024, Pages 47-631931-5244http://hdl.handle.net/10347/33868Fabry disease (FD) is a X-linked rare lysosomal storage disorder caused by deficient α-galactosidase A (α-GalA) activity. Early diagnosis and the prediction of disease course are complicated by the clinical heterogeneity of FD, as well as by the frequently inconclusive biochemical and genetic test results that do not correlate with clinical course. We sought to identify potential biomarkers of FD to better understand the underlying pathophysiology and clinical phenotypes. We compared the plasma proteomes of 50 FD patients and 50 matched healthy controls using DDA and SWATH-MS. The >30 proteins that were differentially expressed between the 2 groups included proteins implicated in processes such as inflammation, heme and haemoglobin metabolism, oxidative stress, coagulation, complement cascade, glucose and lipid metabolism, and glycocalyx formation. Stratification by sex revealed that certain proteins were differentially expressed in a sex-dependent manner. Apolipoprotein A-IV was upregulated in FD patients with complications, especially those with chronic kidney disease, and apolipoprotein C-III and fetuin-A were identified as possible markers of FD with left ventricular hypertrophy. All these proteins had a greater capacity to identify the presence of complications in FD patients than lyso-GB3, with apolipoprotein A-IV standing out as being more sensitive and effective in differentiating the presence and absence of chronic kidney disease in FD patients than renal markers such as creatinine, glomerular filtration rate and microalbuminuria. Identification of these potential biomarkers can help further our understanding of the pathophysiological processes that underlie the heterogeneous clinical manifestations associated with FDengAtribución-NoComercial 4.0 Internacional© 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/)http://creativecommons.org/licenses/by-nc/4.0/Fabry diseaseBiomarkersProteomicsPlasmaClinical phenotypesSexjournal article10.1016/j.trsl.2024.02.006open access