Tear ATG5 as a Potential Novel Biomarker in the Diagnosis of Sjögren Syndrome.

Yong-Soo Byun,Hyun Jung Lee,So-Hyang Chung,Hyung-Seung Kim,Moon Young Choi,Soojung Shin

doi:10.3390/diagnostics11010071

Yong-Soo Byun, Hyun Jung Lee + Show 4 more

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https://doi.org/10.3390/diagnostics11010071

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Abstract

Autophagy has been suggested to have an important role in the pathogenesis of Sjögren syndrome (SS). We previously identified that autophagy related 5 (ATG5) was elevated in the tear and conjunctival epithelial cells of SS dry eyes (DE) compared to non-SS DE. The purpose of this study was to investigate the role of tear ATG5 as a potential biomarker in the diagnosis of SS. To confirm this hypothesis, we evaluated the tear ATG5 concentration, and other ocular tests (Schirmer I, tear breakup time (TBUT), ocular surface staining (OSS) score, ocular surface disease index (OSDI)) in SS and non-DE, and compared their diagnostic performance to discriminate SS from non-SS DE. Tear ATG5 showed the greatest area under the curve (AUC = 0.984; 95% CI, 0.930 to 0.999) among the tests, and a 94.6% sensitivity and 93.6% specificity at a cutoff value of >4.0 ng/mL/μg. Our data demonstrated that tear ATG5 may be helpful as an ocular biomarker to diagnose and assess SS. In the future, the diagnostic power of tear ATG for SS should be validated.

Highlights

Sjögren syndrome (SS) is a systemic autoimmune disorder that affects the exocrine glands such as lacrimal and salivary glands, resulting in dry eye and dry mouth
Tear autophagy related 5 (ATG5) showed the greatest area under the curve (AUC = 0.984; 95% confidence interval (CI), 0.930 to 0.999) among the tests, and a 94.6% sensitivity and 93.6% specificity at a cutoff value of >4.0 ng/mL/μg
Tear ATG5 at a cutoff of >4.0 ng/mL/μg had a positive likelihood ratio (LR) of 14.7 with a 94.6% sensitivity and 93.6% specificity for SS in patients with aqueous deficient-type dry eyes (DE), which was greater than the values of the Schirmer I test, tear breakup time (TBUT), and the ocular surface staining (OSS) score

Summary

Introduction

Sjögren syndrome (SS) is a systemic autoimmune disorder that affects the exocrine glands such as lacrimal and salivary glands, resulting in dry eye and dry mouth. There has been little disagreement among rheumatologists about the diagnosis of SS in a patient with obvious findings on the physical examination of dry eye, dry mouth, and the presence of serologic markers. Against Rheumatism (ACR/EULAR) defined the diagnostic criteria, leading to consensus in research and clinical trial reports [1]. Despite extensive studies over the past decade, the pathogenesis of SS has not been clearly understood. It has been widely known that overexpression of inflammatory cytokines and lymphocyte infiltration with T and NK cells was observed in the affected glands, where secondary B-cell activation and autoantibody production is induced [2]. Environmental trigger and genetic predisposition are thought to contribute to the development of SS [3]

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