Soluble siglec-5 is a novel salivary biomarker for primary Sjogren's syndrome

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). Based on a microarray of peripheral blood mononuclear cells (PBMCs) from patients with primary Sjogren's syndrome (pSS), we aimed to investigate whether soluble sialic acid-binding immunoglobulin-like lectin (siglec)-5 in saliva might be a biomarker 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. The level of salivary siglec-5 was significantly higher in pSS patients (n = 170) compared with HCs (n = 25), non SS sicca patients (n = 78) or patients with systemic lupus erythematosus (SLE) (n = 43) (1346.8 [202.8–4280.0] pg/mL, 6.08 [0–134.0] pg/mL, 195 [0–947.5] pg/mL, and 0 [0–238.7] pg/mL, median [interquartile range], P < 0.001). Salivary siglec-5 level negatively correlated with salivary flow rate (spearman's rho: −0.420, P < 0.001), and positively correlated with ocular surface score (rho: 0.331, P < 0.001) and serum immunoglobulin G level (rho = 0.202, P = 0.008). In ROC analysis, area under the curve was 0.774[0.724–0.826]. With a cut off value of 400 pg/mL, sensitivity and specificity was 0.69 and 0.70 respectively. In validation cohort (45 pSS patients and 45 non SS sicca patients), sensitivity and specificity of siglec-5 was 64.4% and 77.8%, respectively. In conclusion, the level of soluble siglec-5 is significantly higher in the saliva from pSS patients, which reflects the severity of hyposalivation and ocular surface damage. This novel salivary biomarker may provide benefits for pSS diagnosis.