Evaluation of autophagy‐related genes in Egyptian systemic lupus erythematosus patients

Abstract

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.

Evaluation of the interaction between anti-apoptotic Bcl-2 protein family mRNA expression and autophagy gene Bcl-1 expression in Egyptian SLE patients

“…15 Also was in consistent with the results of Ayat et al who showed that the mean levels of Beclin-1, LC-3, and interleukin (IL)-10 transcripts were significantly higher in SLE patients than in the control group. 17 Our results were in agreement with study of Zhen et al who stated that the mean level of Beclin-1 mRNA was significantly higher (p < 0.001) in patients with SLE (9.96×10-4) compared to the control group (7.38×10-4). 18 In our study, the apoptotic Beclin-1 mRNA was positively correlated with SLE disease severity index, r = 0.25; p = 0.0.4, while the anti-apoptotic agents showed insignificant correlation.…”

“…15 Also was in consistent with the results of Ayat et al who showed that the mean levels of Beclin‐1, LC‐3, and interleukin (IL)‐10 transcripts were significantly higher in SLE patients than in the control group. 17…”

Intestinal Macrophage Autophagy and its Pharmacological Application in Inflammatory Bowel Disease

“…Over the few decades since the initial description of autophagy, there are more than 30 autophagy-related genes (ATGs) reported to be vital in the process of autophagy ( Hu, 2019 ; Kamel et al, 2020 ; Zhang et al, 2021 ). The process of autophagy is generally divided into two steps, including the formation of the autophagosome and integration with the lysosome to form the autolysosome ( Wang et al, 2018 ; Yu et al, 2018 ; Colletti et al, 2020 ; Lorincz and Juhasz, 2020 ; Tan and Chen, 2021 ).…”

Pathogenic Single Nucleotide Polymorphisms on Autophagy-Related Genes

“…Moreover, variants of ATG16L1 and other effectors of the ATG12 conjugation system have also been linked to other inflammatory disorders, autoimmune diseases or other complications related to the immune system. In this regard, polymorphisms on ATG5 , ATG10 and ATG16L1 have been associated with Paget’s disease of the bone [ 146 ], and SNPs in ATG5 and ATG7 have been extensively studied in the context of systemic lupus erythematosus [ 147 , 148 , 149 , 150 , 151 , 152 , 153 ]. In addition, several polymorphisms on ATG5 may play a role in the pathogenesis of other autoimmune disorders such as Behçet’s disease [ 154 ], neuromyelitis optica [ 155 ] and systemic sclerosis [ 156 , 157 ].…”