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Autophagy dysfunction may be involved in the pathogenesis of ankylosing spondylitis

Min Tan1, Quan-Bo Zhang1, Tao-Hong Liu1

  • 1Department of Geriatrics, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.

Experimental and Therapeutic Medicine
|August 29, 2020
PubMed

Insights

Ankylosing spondylitis (AS) patients show reduced expression of autophagy genes and long non-coding RNA GAS5 (lncRNA GAS5) in PBMCs. Lower ATG5 and ATG12 levels correlate with AS disease activity, and lncRNA GAS5 aids in AS diagnosis.

Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the spine.
  • Autophagy plays a role in immune regulation, and its dysregulation is implicated in autoimmune diseases.
  • Long non-coding RNAs (lncRNAs), such as GAS5, are emerging as critical regulators in various biological processes, including inflammation.

Purpose of the Study:

  • To investigate the expression levels of autophagy-related genes and lncRNA GAS5 in peripheral blood mononuclear cells (PBMCs) of AS patients.
  • To explore the correlation between these gene expressions and AS disease activity and laboratory parameters.
  • To evaluate the diagnostic value of lncRNA GAS5 for AS.

Main Methods:

  • Quantitative reverse transcription PCR (RT-qPCR) was used to measure mRNA levels of autophagy genes (LC3, Beclin1, ATG3, ATG5, ATG12, ATG16L1) and lncRNA GAS5 in PBMCs from 60 AS patients and 30 healthy controls (HC).
  • Spearman correlation analysis was performed to assess relationships between gene expression and clinical/laboratory parameters.
  • Receiver operating characteristic (ROC) curve analysis was employed to determine the diagnostic accuracy of lncRNA GAS5.

Main Results:

  • AS patients exhibited significantly lower expression of LC3, ATG5, ATG12, ATG16L1, and lncRNA GAS5 compared to HCs.
  • Patients with active AS showed lower ATG5 and ATG12 mRNA levels than those with inactive AS, with negative correlations to disease activity indexes.
  • lncRNA GAS5 expression positively correlated with Beclin1, ATG3, ATG5, ATG12, and ATG16L1. The ROC curve analysis indicated an area under the curve of 0.808 for lncRNA GAS5 in diagnosing AS.

Conclusions:

  • Patients with AS demonstrate reduced expression of key autophagy-related genes and lncRNA GAS5 in PBMCs.
  • The decreased expression of ATG5 and ATG12 is associated with AS disease severity and activity.
  • lncRNA GAS5 serves as a potential diagnostic biomarker for ankylosing spondylitis.
Keywords:
ankylosing spondylitisautophagy-related genesdiagnosisdisease severity and activitylong non-coding RNA growth arrest-specific 5

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