A non-invasive model for diagnosis of primary Sjogren’s disease based on salivary biomarkers, serum autoantibodies, and Schirmer’s test

• Published in: Arthritis research & therapy Vol. 26; no. 1; pp. 217 - 11
• Main Authors: Zhang, Xinwei, Liao, Zhangdi, Chen, Yangchun, Lu, Huiqin, Wang, Aodi, Shi, Yingying, Zhang, Qi, Wang, Ying, Li, Yan, Lan, Jingying, Chen, Chubing, Deng, Chaoqiong, Zhuang, Wuwei, Liu, Lingyu, Qian, Hongyan, Chen, Shiju, Li, Zhibin, Shi, Guixiu, Liu, Yuan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19.12.2024; BioMed Central; BMC
• Subjects: Adult; Aged; Autoantibodies - analysis; Autoantibodies - blood; Autoantibodies - immunology; Biological markers; Biomarkers; Biomarkers - analysis; Biomarkers - blood; Chromatography, Liquid - methods; Clusterin - analysis; Clusterin - blood; Diagnosis; Enzyme-Linked Immunosorbent Assay; Female; Health aspects; Humans; Male; Mass spectrometry; Methods; Middle Aged; Physiological aspects; Proteomics; ROC Curve; Saliva - immunology; Salivary glands; Sjogren's syndrome; Sjogren's Syndrome - blood; Sjogren's Syndrome - diagnosis; Sjogren's Syndrome - immunology; Sjögren’s disease; Tandem Mass Spectrometry - methods; China; Biomarkers; Sjögren’s disease; Proteomics
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-024-03459-7

Minor salivary gland (MSG) biopsy is a critical but invasive method for the classification of primary Sjögren's disease (pSjD). Here we aimed to identify salivary proteins as potential biomarkers and to establish a non-invasive prediction model for pSjD. Liquid chromatography-tandem mass spectrometry was conducted on whole saliva samples from patients with pSjD and non-Sjögren control subjects (non-pSjD). Proteins involved in immune processes were upregulated in the pSjD group, such as complement C3 (C3), complement factor B (CFB), clusterin (CLU), calreticulin (CALR), and neutrophil elastase (NE), which were further confirmed by ELISA. Multivariate logistic regression analyses were performed to identify markers that differentiated pSjD from non-pSjD; receiver operating characteristic (ROC) curves were constructed. A diagnostic model based on the combination of salivary biomarkers (CFB, CLU, and NE), serum autoantibodies (anti-SSA /Ro60 and anti-SSA/Ro52), and Schirmer's test was evaluated in 186 patients (derivation cohort) with replication in 72 patients (validation cohort). In multivariate analyses, CFB, CLU, and NE were independent predictors of pSS. A model based on the combination of salivary biomarkers (CFB, CLU, and NE), serum autoantibodies (anti-SSA and anti-Ro52), and Schirmer's test achieved significant discrimination of pSS. In the derivation cohort, the area under curve (AUC) of the ROC was 0.930 (95% CI 0.877-0.965, P < 0.001), with a sensitivity and specificity of 84.85% and 92.45%, respectively. Notably, similar results were obtained in a validation cohort. The 6-biomarker panel could provide a novel non-invasive tool for the classification of pSjD.