Biomedical Research Center, Qatar University, Doha, Qatar.
Eur Rev Med Pharmacol Sci. 2023 Sep;27(18):8463-8485. doi: 10.26355/eurrev_202309_33772.
Autoimmune diseases (ADs) are common conditions in which an individual's immune system reacts against its healthy cells. This condition is a common cause of morbidity and mortality, with an estimated prevalence ranging from 5 per 100,000 to more than 500 per 100,000. According to the National Stem Cell Foundation (NSCF), ADs are prevalent in about 4% of the world's population, which creates a burden on society due to the high treatment cost. ADs show a clear gender bias with a higher prevalence among women, occurring at a rate of 2:1 female-to-male ratio. The etiology of ADs includes genetic and environmental factors. ADs are more likely to develop in genetically susceptible individuals. The higher concordance ratio between monozygotic twins compared to dizygotic twins or other siblings validates the role of genetic factors in the pathogenesis of many ADs. ADs diagnosis includes conventional immunoassay such as indirect immunofluorescence, complement fixation, passive agglutination, autoantibodies detection, and most recent advances, including multiplex platforms such as microspots, line-blot, addressable microbeads and barcoded nanoparticles that allow multiplex parallel testing of autoantibodies. ADs treatment includes biological and synthetic drugs that block many pathways and components of the immune system, including Janus kinase (JAK) inhibitors, non-receptor tyrosine-protein kinase (TYK2), and other cytokines. Generally, recent immune-modulatory drugs used in ADs treatment are non-disease specific with broad action and are associated with many side effects like infection and malignant diseases. Furthermore, gene therapy seeks to control the levels of proinflammatory cytokine molecules and lymphocyte infiltration through the delivery and expression of therapeutic genes. Recent genomic-wide association studies (GWAS) have allowed the identification of various genetic loci associated with disease susceptibility and have revealed candidate genes that can be used in targeted therapeutics. This review summarizes recent literature on the genetic factors associated with susceptibility to the 11 most common ADs, namely: Type 1 diabetes mellitus (T1DM), Multiple sclerosis (MS), Grave's disease, Sjögren's syndrome (SS), Celiac disease, Hashimoto's thyroiditis (HT), Anti-phospholipid syndrome (APS), Autoimmune hemolytic anemia, Rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), and Scleroderma (systemic sclerosis).
自身免疫性疾病(ADs)是一种常见病症,在这种病症中,人体的免疫系统会攻击自身的健康细胞。这种病症是发病率和死亡率的常见原因,据估计,其患病率在每 10 万人中有 5 例至超过 500 例不等。根据国家干细胞基金会(NSCF)的数据,ADs 在世界人口中较为常见,约占 4%,这给社会带来了沉重的治疗负担。ADs 存在明显的性别偏向,女性发病率更高,男女比例为 2:1。ADs 的病因包括遗传和环境因素。在遗传易感性个体中,ADs 更易发生。同卵双胞胎之间的一致性比率明显高于异卵双胞胎或其他兄弟姐妹,这验证了遗传因素在许多 ADs 发病机制中的作用。ADs 的诊断包括间接免疫荧光、补体固定、被动凝集、自身抗体检测等传统免疫检测方法,以及最近的进展,包括微点、线印迹、可寻址微珠和条形码纳米颗粒等多重平台,这些平台允许对自身抗体进行多重平行检测。ADs 的治疗包括生物和合成药物,这些药物可以阻断免疫系统的许多途径和成分,包括 Janus 激酶(JAK)抑制剂、非受体酪氨酸蛋白激酶(TYK2)和其他细胞因子。一般来说,最近用于 ADs 治疗的免疫调节药物是非特异性的,作用广泛,与感染和恶性疾病等许多副作用相关。此外,基因治疗旨在通过递送和表达治疗基因来控制促炎细胞因子分子和淋巴细胞浸润的水平。最近的全基因组关联研究(GWAS)已经确定了与疾病易感性相关的各种遗传位点,并揭示了可用于靶向治疗的候选基因。本综述总结了最近关于与 11 种最常见 ADs 易感性相关的遗传因素的文献,这些 ADs 分别是:1 型糖尿病(T1DM)、多发性硬化症(MS)、格雷夫斯病、干燥综合征(SS)、乳糜泻、桥本甲状腺炎(HT)、抗磷脂综合征(APS)、自身免疫性溶血性贫血、类风湿关节炎(RA)、系统性红斑狼疮(SLE)和硬皮病(系统性硬化症)。