Microbiology and Immunology Department, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Microbiology and Immunology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
Int J Rheum Dis. 2020 Aug;23(9):1226-1232. doi: 10.1111/1756-185X.13910. Epub 2020 Aug 12.
Disturbances in autophagy are known to be implicated in autoimmune disorders. Many studies have connected polymorphisms in autophagy-related gene 5 (ATG-5) to systemic lupus erythematosus (SLE). Our aim was the determination of the expression level of ATG-5, Beclin-1 and microtubule-associated protein-light chain 3 (LC-3) in Egyptian SLE patients to investigate the impact of disturbances in autophagy genes on the incidence and progression of the disease. Also, we investigated the incidence of single nucleotide polymorphism (SNP) rs573775 in ATG-5 gene among Egyptian SLE patients. Our results showed that the mean levels of Beclin-1, LC-3 and interleukin (IL)-10 transcripts were significantly higher in SLE patients compared to healthy controls. The previous transcripts were positively correlated with SLE Disease Activity Index (SLEDAI). Beclin-1 and LC-3 transcripts were negatively correlated to complement component 3 (C3) levels. Only LC-3 transcripts were negatively correlated to complement component 4 (C4). The rs573775 SNP of ATG-5 with the variant allele was significantly associated with disease susceptibility, conferring a higher risk of SLE development. This variant allele was more prevalent in patients below 30 years, patients with anemia and in patients with anti-double-stranded DNA (dsDNA), confirming the essential role of ATG-5 polymorphism in the susceptibility of Egyptian patients to SLE.
自噬紊乱与自身免疫性疾病有关。许多研究将自噬相关基因 5 (ATG-5) 的多态性与系统性红斑狼疮 (SLE) 联系起来。我们的目的是确定埃及 SLE 患者中 ATG-5、Beclin-1 和微管相关蛋白轻链 3 (LC-3) 的表达水平,以研究自噬基因的紊乱对疾病的发生和进展的影响。此外,我们还研究了 ATG-5 基因中单核苷酸多态性 (SNP) rs573775 在埃及 SLE 患者中的发生率。我们的结果表明,与健康对照组相比,SLE 患者的 Beclin-1、LC-3 和白细胞介素 (IL)-10 转录本的平均水平显著升高。上述转录本与 SLE 疾病活动指数 (SLEDAI) 呈正相关。Beclin-1 和 LC-3 转录本与补体成分 3 (C3) 水平呈负相关。只有 LC-3 转录本与补体成分 4 (C4) 呈负相关。ATG-5 基因的 rs573775 SNP 与变异等位基因显著相关,增加了 SLE 发病的风险。该变异等位基因在 30 岁以下的患者、贫血患者和抗双链 DNA (dsDNA) 患者中更为常见,证实了 ATG-5 多态性在埃及患者对 SLE 易感性中的重要作用。