Background/Purpose:  Autophagy is a process of cellular self-digestion by enzymes originating within the lysosome of the cell. Autophagy primarily acts as a survival mechanism by removing damaged and dysfunctional proteins or organelles. It is well documented that autophagy has a potentially pivotal role in the induction and regulation of inflammatory responses by immune cells. However, a role of autophagy in ankylosing spondylitis has not been clearly elucidated and the association of autophagy-related gene expression levels with inflammatory or osteoproliferative processes observed in ankylosing spondylitis has not been reported. This study was performed to determine the expression levels of several key autophagy-related genes in patients with ankylosing spondylitis and investigate whether autophagy-related gene expression levels are associated with clinical parameters of ankylosing spondylitis and the production of inflammatory cytokines to elucidate the role of autophagy in pathogenesis of AS.

Methods:  PBMCs from 43 AS patients and 40 healthy controls were obtained and mRNA expression levels of Atg genes (LC3, beclin1, and ATG5) were determined using quantitative real-time PCR. Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP and modified Stoke AS Spinal Score (mSASSS) were assessed at the time of blood sampling. Serum concentrations of TNF-alpha, IL-17, and IL-23 in AS patients were determined using enzyme-linked immunosorbent assays.

Results:  LC3, beclin1, and ATG5 mRNAs were constitutively expressed in PBMCs of AS patients and healthy controls; however, expression of all three genes was significantly decreased in PBMCs of AS patients compared with those from controls. Expression levels of the autophagy-related genes were not significantly correlated with ASDAS-CRP or serum TNF-alpha, IL-17, and IL-23 concentrations. However, LC3 and beclin1 mRNA levels showed significant negative correlations with mSASSS of AS patients (r = -0.805, p<0.01 for LC3 and r = -0.712, p<0.01 for beclin1).

Conclusion:  AS patients have decreased autophagy-related gene expressions and AS patients with more advanced spinal damage have further decreased LC3 and beclin1 expression levels. These results suggest that AS patients have defective autophagy activity and that compromised autophagy may contribute to the progression of spinal damage in AS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/decreased-expression-of-autophagy-genes-and-their-association-with-spinal-damage-in-patients-with-ankylosing-spondylitis/