Growth Arrest-Specific 6 Protein in Patients with Sjögren Syndrome: Determination of the Plasma Level and Expression in the Labial Salivary Gland.

Chen-Hung Chen,Yi-Shing Shieh,Yi-Jen Peng,Chien-Hsing Lee,Hsiang-Cheng Chen,Yuh-Feng Lin,Yi-Jen Hung,Chi-Ching Chang,Jose Crispin

doi:10.1371/journal.pone.0139955

Abstract

AimsGrowth arrest-specific protein 6 (Gas6) is a vitamin K-dependent protein expressed by endothelial cells and leukocytes that are involved in cell survival, migration, and proliferation in response to inflammatory processes. The aim of this study was to assess the implications of Gas6 in Sjögren syndrome (SS) and its expression in the labial salivary gland.Methods and ResultsA total of 254 adults, including 159 with primary Sjögren syndrome (pSS), 34 with secondary Sjögren syndrome (sSS), and 61 normal controls, were recruited. Plasma Gas6 concentrations were determined, and Gas6 expressions in labial salivary gland (LSG) tissues from controls and pSS and sSS patients were also evaluated. Plasma Gas6 concentrations were significantly lower among patients with pSS than normal controls (13.5 ± 8.6 vs. 19.9 ± 13.4 ng/ml, p < 0.001). There were, however, no significant differences in plasma Gas6 levels between pSS and sSS patients (13.5 ± 8.6 vs. 16.9 ± 11.2 ng/ml, p = 0.068). In multivariate logistic regression analysis, after adjustment for white blood cell count, hemoglobin level, platelet count, lymphocyte count, and C3 and C4 levels, lower plasma Gas6 concentrations were significantly associated with an increased risk of SS. Moreover, by using a semi-quantitative scale to evaluate Gas6 expression in LSG tissues, Gas6 expression was found to be markedly lower in LSG tissues from pSS patients than in tissues from normal controls.ConclusionsDecreased plasma Gas6 concentration and LSG expression were associated with pSS. As such, Gas6 may represent a novel independent risk factor for pSS, with a potential role in salivary gland inflammation and dysfunction.

Highlights

Sjögren syndrome (SS) is a chronic inflammatory disease that affects the exocrine glands, the salivary and lacrimal glands
In multivariate logistic regression analysis, after adjustment for white blood cell count, hemoglobin level, platelet count, lymphocyte count, and C3 and C4 levels, lower plasma Growth arrest-specific protein 6 (Gas6) concentrations were significantly associated with an increased risk of SS
Decreased plasma Gas6 concentration and labial salivary gland (LSG) expression were associated with primary Sjögren syndrome (pSS)

Summary

Introduction

Sjögren syndrome (SS) is a chronic inflammatory disease that affects the exocrine glands, the salivary and lacrimal glands. Growth arrest-specific protein 6 (Gas6) is the most recently identified member of the family of plasma vitamin K-dependent proteins. It was cloned and characterized in 1993 and found to be similar to plasma anticoagulant protein S [10]. Among the pathways implicated in SS pathogenesis, elevated in-situ apoptosis of SGEC and the release of autoantigen-containing apoptotic blebs, as well as the secretion of exosomes that are involved in the transfer of antigens to antigen-presenting cells, are hypothesized as the initial insult of SS [19], [20], [21], [22], [23].

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