Defective autophagy activity and its association with spinal damage in patients with ankylosing spondylitis.
OBJECTIVE
This study was performed to determine the expression levels of autophagy-related genes in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and to investigate their associations with clinical parameters reflecting disease activity and radiographic progression and with cytokine levels of AS patients.


METHODS
PBMCs from 53 AS patients and 49 healthy controls were obtained and mRNA expression levels of LC3, belcin1, 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-α, IL-17, and IL-23 were determined in the serum of AS patients using enzyme-linked immunosorbent assay.


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-α, 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).


CONCLUSIONS
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.
Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: mcpark@yuhs.ac.
Min-Chan
MC
Park
Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Hye Won
HW
Kim
Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Sang-Won
SW
Lee
Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Jason Jungsik
JJ
Song
Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Yong-Beom
YB
Park
D000328:Adult; D001343:Autophagy / Q000235:genetics*; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D012720:Severity of Illness Index; D013131:Spine / Q000503:physiopathology; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*
D016207:Cytokines; D012333:RNA, Messenger
Ankylosing spondylitis; Autophagy; Cytokine; Disease activity; Spinal damage