Increased MRNA Expression Of Autophagy-associated Gene TFEB In PBMC In Children With Systemic Lupus Erythematosus

BackgroundAimSystemic lupus erythematosus(SLE),is the most important autoimmune disease characterized by the generation of antinuclear antibodies and failure of multiple tolerance checkpoints. Autophagy is a homeostasis mechanism with double membrane in almost all types of cells which can engulf intracellular content, sequestration of the cytoplasm into the lysosome and then degrade it with lysosome. Previous studies showed autophagy-related genes such as ATG5% ATG7 or P62 were involved in the mechanisms of autoimmune diseases. Transcription factor EB (TFEB), an autophagy-associated gene plays a key role for lysosomal biogenesis. However, its role on the mechanism of autoimmune diseases remains largely unknown. The objective of this study is to investigate TFEB gene expression and gain an insight into the underlying genetic basis of systemic lupus erythematosus (SLE) in children.MethodsThe patient subgroups were untreated and active systemic lupus erythematosus (SLE1, n=5), treated and inactive SLE (SLE2, n=5),and patients with congenital heart disease before surgery (control, n=5). Peripheral blood mononuclear cells (PBMCs) were isolated using density gradient centrifugation with Ficoll-Paque Plus from the newly extracted blood of children with SLE or control. RT-PCR was designed to determine the mRNA expression levels of autophagy-associated genes of TFEB* ATG5> ATG7 or P62.Autophagy in of PBMCs of SLE patient was observed via transmission electron microscopy (TEM).Results1. Compared to patients from control group, mRNA expressions of TFEB、ATG5 or ATG7 genes were expressed at significantly higher levels in children from SLE1 group (ZTFEB=-2.62,PTFEB=0.008; ZATG5=-2.14,PATG5=0.016; ZATG7=-2.31,PATG7=0.016). Compared to SLE1 group, decreased levels of TFEB or ATG7 but not ATG5 genes mRNA expressions were observed in patients from SLE2 group (ZTFEB=-1-98,PTFEB<0.047; ZATG7=-2.40,PATG7=r0.016,). However, there was no statistical difference in mRNA expressions of P62 gene in patients between SLE1, SLE2 and control groups.2. The shape and the number of autophagy were quite different under TEM between SLE1 and control group.3.ConclusionAn up-regulation of autophagy-associated genes TFEB, ATG5 or ATG7 mRNA may be involved the mechanisms of SLE. Decreased mRNA expressions of TFEB or ATG7 in treated and inactive SLE suggest that they could be the targets for potential therapeutic modulation.