AB0532 SOLUBLE SIGLEC-5 IS A NOVEL SALIVARY BIOMARKER FOR PRIMARY SJOGREN’S SYNDROME
Authors: Jennifer Lee, Moon Young Kim, Sung-Hwan Park
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Despite advances in the understanding of the pathogenesis, disease-specific biomarkers have not been included in the classification criteria for Primary Sjogren's syndrome (pSS). <h3>Objectives:</h3> Based on the microarray of peripheral blood mononuclear cell (PBMC) of pSS patients, we aimed to investigate whether sialic acid-binding immunoglobulin-like lectin (siglec)-5 might serve as a biomarker for pSS. <h3>Methods:</h3> Microarray of PBMCs obtained from 26 pSS patients and 10 healthy control (HC)s was performed to screen potential biomarkers for pSS. The concentration of siglec-5 in saliva and sera was determined by ELISA. Clinical parameters related with pSS were obtained from pSS registry and correlation with salivary siglec-5 level was evaluated. Receiver operating curve (ROC) analysis was performed to determine cut off value. A separate validation cohort consisted of subjects with suspicious pSS was evaluated to determine the performance. <h3>Results:</h3> The level of salivary siglec-5/14 was significantly higher in pSS patients (n=170) compared with HCs (n=25) or non SS sicca patients (n=78) (1346.8 [202.8-4280.0] pg/mL, 6.08 [0-134.0] pg/mL, and 195 [0-947.5] pg/mL, median [interquartile range], P&lt;0.001), meanwhile the serum level was not different between the groups. Clinical parameters were available in 170 patients in pSS registry. Salivary siglec-5 level negatively correlated with salivary flow rate (spearman's rho: -0.420, P&lt;0.001), and positively correlated with ocular surface score (rho: 0.331, P&lt;0.001) and serum immunoglobulin G level (rho = 0.202, P=0.008). However, the level of salivary siglec-5 was not correlated with ESSDAI or focus score. On ROC analysis, area under the curve was 0.774(0.724-0.826). With cut off value 400pg/mL, sensitivity and specificity was 0.69 and 0.70 respectively. In validation cohort (45 pSS patients and 45 non SS sicca patients) where patients without sicca symptom but have 1 or more positive items in ESSDAI were included, sensitivity and specificity of siglec-5 was 64.4% and 77.8%, respectively. <h3>Conclusion:</h3> The level of soluble siglec-5 is significantly increased in the saliva of pSS patients and reflects the severity of hyposalivation and ocular surface damage. Although the mechanism of the contribution to gland dysfunction is unclear yet, this easily obtainable salivary biomarker may add benefits on the diagnosis of pSS. <h3>References</h3> [1] Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjogren's syndrome: A consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis 2017;76:9-16. [2] Katsiougiannis S, Wong DT. The Proteomics of Saliva in Sjogren's Syndrome. Rheum Dis Clin North Am 2016;42:449-56. [3] Lee J, Lee J, Kwok SK, et al. Janus kinase 1 inhibition suppresses interferon-induced B cell activating factor production in human salivary gland: potential therapeutic strategy for primary Sjogren's syndrome. Arthritis Rheumatol 2018. [4] Macauley MS, Crocker PR, Paulson JC. Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol 2014;14:653-66. [5] Ali SR, Fong JJ, Carlin AF, et al. Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus. J Exp Med 2014;211:1231-42. <h3>Disclosure of Interests:</h3> None declared