Department of Biomedical Sciences, Faculty of Medicine, Collegium Medicum, Cardinal Stefan Wyszynski University, Wóycickiego Street 1/3, 01-938 Warsaw, Poland.
Students Scientific Association "Immunis", Cardinal Stefan Wyszynski University, Dewajtis Street 5, 01-815 Warsaw, Poland.
Int J Mol Sci. 2024 Aug 20;25(16):9034. doi: 10.3390/ijms25169034.
Wilson's disease (WD) is a rare, autosomal recessive disorder of copper metabolism caused by pathogenic mutations in the gene. Cellular copper overload is associated with impaired iron metabolism. Oxidative stress, cuproptosis, and ferroptosis are involved in cell death in WD. The clinical picture of WD is variable. Hepatic/neuropsychiatric/other symptoms may manifest in childhood/adulthood and even old age. It has been shown that phenotypic variability may be determined by the type of genetic variants as well as the influence of various genetic/epigenetic, environmental, and lifestyle modifiers. In 1976, immunological abnormalities were first described in patients with WD. These included an increase in IgG and IgM levels and a decrease in the percentage of T lymphocytes, as well as a weakening of their bactericidal effect. Over the following years, it was shown that there is a bidirectional relationship between copper and inflammation. Changes in serum cytokine concentrations and the relationship between cytokine gene variants and the clinical course of the disease have been described in WD patients, as well as in animal models of this disease. Data have also been published on the occurrence of antinuclear antibodies (ANAs), antineutrophil cytoplasmic antibodies (ANCAs), anti-muscle-specific tyrosine kinase antibodies, and anti-acetylcholine receptor antibodies, as well as various autoimmune diseases, including systemic lupus erythematosus (SLE), myasthenic syndrome, ulcerative colitis, multiple sclerosis (MS), polyarthritis, and psoriasis after treatment with d-penicillamine (DPA). The occurrence of autoantibodies was also described, the presence of which was not related to the type of treatment or the form of the disease (hepatic vs. neuropsychiatric). The mechanisms responsible for the occurrence of autoantibodies in patients with WD are not known. It has also not been clarified whether they have clinical significance. In some patients, WD was differentiated or coexisted with an autoimmune disease, including autoimmune hepatitis or multiple sclerosis. Various molecular mechanisms may be responsible for immunological abnormalities and/or the inflammatory processes in WD. Their better understanding may be important for explaining the reasons for the diversity of symptoms and the varied course and response to therapy, as well as for the development of new treatment regimens for WD.
威尔逊病（WD）是一种罕见的常染色体隐性遗传性铜代谢疾病，由 基因的致病性突变引起。细胞内铜过载与铁代谢受损有关。氧化应激、铜死亡和铁死亡参与 WD 中的细胞死亡。WD 的临床表现多种多样。肝/神经精神/其他症状可在儿童/成年期甚至老年期出现。已经表明，表型变异性可能由遗传变异的类型以及各种遗传/表观遗传、环境和生活方式修饰剂的影响决定。1976 年，首次在 WD 患者中描述了免疫异常。这些异常包括 IgG 和 IgM 水平升高，T 淋巴细胞百分比降低，以及其杀菌作用减弱。在随后的几年中，表明铜和炎症之间存在双向关系。在 WD 患者以及该疾病的动物模型中，已经描述了血清细胞因子浓度的变化以及细胞因子基因变异与疾病临床过程之间的关系。也有关于抗核抗体（ANA）、抗中性粒细胞胞质抗体（ANCA）、抗肌肉特异性酪氨酸激酶抗体和抗乙酰胆碱受体抗体以及各种自身免疫性疾病（包括系统性红斑狼疮（SLE）、肌无力综合征、溃疡性结肠炎、多发性硬化症（MS）、多关节炎和银屑病）发生的数据）在用 D-青霉胺（DPA）治疗后。还描述了自身抗体的发生，其存在与治疗类型或疾病形式（肝性与神经精神性）无关。WD 患者发生自身抗体的机制尚不清楚。它们是否具有临床意义也不清楚。在一些患者中，WD 与自身免疫性疾病（包括自身免疫性肝炎或多发性硬化症）相区别或共存。各种分子机制可能负责 WD 中的免疫异常和/或炎症过程。更好地理解它们对于解释症状多样性以及对治疗的不同反应和反应的原因，以及为 WD 开发新的治疗方案可能很重要。
