Systemic inflammation in Fabry disease: a longitudinal immuno-genetic analysis based on variant stratification
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: 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. Objectives: To characterize inflammatory and immunological profiles in a genetically stratified familial cohort with Fabry disease and explore genotype-dependent immune activation patterns. Design: Retrospective, longitudinal study of 11 patients from three interconnected families carrying distinct pathogenic GLA variants. Methods: 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. Results: All patients exhibited chronic inflammation regardless of genotype. The c.53dup variant showed prominent humoral activation, IVS4+1G>A had complement-mediated activation with a cardiorenal phenotype, and c.845C>T showed mild persistent inflammation. Correlations included CRP and IgG, and complement factors with fibrinogen in the splicing variant group. Conclusion: 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.
Authors: Haylen Marín Gómez, Miguel López-Garrido
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4414133806