Moura Alana Pimentel, Hammerschmidt Tatiane Grazieli, Guerreiro Gilian, Aguilar Camila, Faverzani Jéssica Lamberty, Lopes Franciele Fátima, de Oliveira Poswar Fabiano, Giugliani Roberto, Deon Marion, Vargas Carmen Regla
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, Porto Alegre, RS, 235090035-903, Brazil.
Centro de Vacinas HCPA - Escritório de Projetos e Parcerias Estratégicas - HCPA, Porto Alegre, RS, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):4211-4218. doi: 10.1007/s00210-024-03499-5. Epub 2024 Oct 22.
Fabry disease (FD) is an X-linked recessive lysosomal storage disorder, characterized by a deficiency of α-galactosidase, which causes the progressive accumulation of glycosphingolipids, especially globotriaosylsphingosine (Gb3), in lysosomes across multiple organs. Substrate deposition, associated with tissue damage in FD, also contributes to the emergence of a pro-inflammatory state presented by some patients. We investigated pro- and anti-inflammatory cytokines, and the expression of inflammation-associated genes in treated FD patients, as well as oxidative parameters. We found a decrease in the production of cytokines IL-1β, IL-6, IL-10, and TNF-α in male FD patients and a normalization of redox status in male and female FD patients, once the levels of protein, lipid oxidation, and nitrite and nitrate content were like healthy individuals. Our results suggest that long-term ERT in men with FD contributes to the reduction of a pro-inflammatory scenario and a decrease of oxidative damage in patients, reflecting greater control throughout the disease and in the multisystemic changes characteristic of this disorder. These findings lead us to believe that long-term ERT can improve the redox status and protect these individuals against oxidative and nitrative stress, as well as the inflammatory process.
法布里病（FD）是一种X连锁隐性溶酶体贮积症，其特征是α-半乳糖苷酶缺乏，导致糖鞘脂尤其是球三糖基鞘氨醇（Gb3）在多个器官的溶酶体中进行性蓄积。底物沉积与FD中的组织损伤相关，也促使部分患者出现促炎状态。我们研究了接受治疗的FD患者体内的促炎和抗炎细胞因子、炎症相关基因的表达以及氧化参数。我们发现男性FD患者体内细胞因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和肿瘤坏死因子-α（TNF-α）的产生减少，并且男性和女性FD患者的氧化还原状态恢复正常，因为蛋白质、脂质氧化以及亚硝酸盐和硝酸盐含量水平与健康个体相似。我们的结果表明，对男性FD患者进行长期酶替代疗法（ERT）有助于减轻促炎情况并降低患者的氧化损伤，这反映出在整个疾病过程以及该疾病特征性的多系统变化中得到了更好的控制。这些发现使我们相信，长期ERT可以改善氧化还原状态，并保护这些个体免受氧化和硝化应激以及炎症过程的影响。
