Marín Gómez Haylen, López-Garrido Miguel
Internal Medicine, Hospital Universitario San Agustín de Linares, Área de Gestión Sanitaria Norte de Jaén - Servicio Andaluz de Salud (SSPA), Avenida San Cristóbal s/n, Linares, Jaén 23700, Spain.
Cardiology, Hospital Universitario San Agustín de Linares, Área de Gestión Sanitaria Norte de Jaén - Servicio Andaluz de Salud (SSPA), Spain.
Ther Adv Rare Dis. 2025 Sep 11;6:26330040251375498. doi: 10.1177/26330040251375498. eCollection 2025 Jan-Dec.
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.
To characterize inflammatory and immunological profiles in a genetically stratified familial cohort with Fabry disease and explore genotype-dependent immune activation patterns.
Retrospective, longitudinal study of 11 patients from three interconnected families carrying distinct pathogenic GLA variants.
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.
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.
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.
法布里病是一种由GLA基因突变引起的多系统溶酶体疾病。尽管传统上认为是由于球三糖神经酰胺（Gb3）在溶酶体中蓄积所致，但最近的证据表明，持续性全身炎症在其发病机制中起关键作用，即使在疾病早期也是如此。
对一个有法布里病的遗传分层家系队列中的炎症和免疫特征进行表征，并探索基因型依赖性免疫激活模式。
对来自三个有亲属关系的家庭的11名携带不同致病性GLA变异的患者进行回顾性纵向研究。
我们分析了炎症生物标志物（C反应蛋白、铁蛋白、纤维蛋白原）和免疫标志物（IgG、IgM、IgE、补体C3/C4、抗酶替代治疗抗体）的纵向数据以及临床变量。采用多变量相关性和无监督聚类技术探索免疫表型模式。
所有患者均表现出慢性炎症，与基因型无关。c.53dup变异表现出显著的体液激活，IVS4+1G>A变异具有补体介导的激活并伴有心肾表型，c.845C>T变异表现出轻度持续性炎症。相关性包括剪接变异组中的CRP与IgG以及补体因子与纤维蛋白原。
法布里病中的炎症不仅是底物蓄积的结果，而且是疾病的一个活跃且早期的驱动因素。基于免疫机制的初步炎症表型可能会指导未来的个性化治疗策略。
