Autophagy dysfunction may be involved in the pathogenesis of ankylosing spondylitis.

Abstract

The present study aimed to investigate the expression and significance of the mRNA of genes associated with autophagy and long non-coding RNA (lncRNA) GAS5 in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS). The mRNA levels of microtubule-associated protein light chain 3 (LC3), Beclin1, autophagy-related gene (ATG)3, ATG5, ATG12, ATG 16 ligand 1 (ATG16L1) and lncRNA growth arrest-specific 5 (GAS5) in PBMCs from 60 patients with AS and 30 healthy controls (HC) were examined by reverse transcription-quantitative PCR. The correlations between the levels of LC3, Beclin1, ATG3, ATG5, ATG12 and ATG16L1 mRNA as well as lncRNA GAS5 levels with disease activity and laboratory parameters in patients with AS were determined by Spearman correlation analysis. In addition, the diagnostic value of lncRNA GAS5 for AS was explored through establishing a receiver operating characteristic (ROC) curve. The results indicated that, compared to the HCs, patients with AS had lower expression levels of LC3, ATG5, ATG12, ATG16L1 and lncRNA GAS5 in their PBMCs. Compared with those in patients with inactive AS, the levels of ATG5 and ATG12 were lower than those in patients with active AS. Of note, ATG5 and ATG12 mRNA levels were negatively correlated with disease activity indexes. lncRNA GAS5 was positively correlated with the expression of Beclin1, ATG3, ATG5, ATG12 and ATG16L1. The area under the ROC curve for the use of lncRNA GAS5 expression to diagnose AS was 0.808 with a 95% CI of 0.714-0.902. In conclusion, patients with AS had decreased expression of genes associated with autophagy and lncRNA GAS5. The extent of the reduction in ATG5 and ATG12 expression levels in patients with AS was correlated with the disease severity and activity. Furthermore, lncRNA GAS5 was a diagnostic indicator of AS.