Background/Purpose: The EULAR SS Disease Activity Index (ESSDAI) is currently used as an objective evaluation method of clinical disease activity in clinical research into primary Sjogren’s syndrome (pSS). This comprehensive indicator reflects patient signs and symptoms and organ involvement. However, a useful substitute serum biomarker of disease activity has not been established. Although several proteomic investigations of small and large salivary and lachrymal glands have been recently reported, information on serum protein is insufficient. Here, we aimed to reveal a distinct serum protein signature of pSS and identify novel biomarkers of disease activity.Methods: We studied 90 serum samples from 30 pSS patients, 30 untreated rheumatoid arthritis (RA) patients as non-SS autoimmune disease controls, and 30 healthy control (HC) subjects. 1128 serum proteins, including inflammatory cytokines and chemokines, were quantitatively measured by comprehensive high-throughput proteomics assay using nucleic acid aptamers (SOMAscan™ Assay; Somalogic Inc., CO, USA). Associations between serum protein concentrations, clinical indicators and laboratory test results were statistically analyzed.Results: After exclusion of 28 proteins for statistical reasons, 1100 of 1128 proteins in 90 subjects were analyzed. We first screened differentially up- and down-regulated proteins among the three groups, by which 195 proteins, including some overlap (85; pSS vs HC, 124; RA vs HC, 81; pSS vs RA), were statistically extracted (p<0.05 in the t-test and U-test, and fold change ≥ 1.2 or ≤0.83). Sixty proteins were up-regulated in pSS compared with HC, including BAFF (pSS patients/healthy control subjects: 9.4-fold), I-Tac (1.82-fold), vWF (1.57-fold), β2-microglobulin (1.47-fold), while 25 were down-regulated, including Immunoglobulin (Ig) D (0.21-fold), CTAP-III (0.79-fold), and GPIIbIIIa (0.83-fold). Enrichment analysis for characterization of up-regulated genes identified these as cytokines and chemokines including TNF-associated molecules and coagulation factors, indicating a serum protein signature in pSS. Multivariate analysis of these 60 proteins and ESSDAI identified 15 proteins with a statistically positive correlation, including TNF-associated molecules (BAFF, sCD163, TRAIL1-R4 and others), LAG-3, β2-microglobulin, and others.Conclusion This comprehensive proteomics analysis highlighted a dysregulated immunity and coagulation signature in patients with pSS. Fifteen up-regulated proteins were found to be correlated with disease activity. These proteins are candidate serum biomarkers for use in the clinical prediction of disease activity of pSS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/distinct-serum-protein-signature-and-novel-biomarkers-of-primary-sjogrens-syndrome-revealed-by-comprehensive-high-throughput-proteomic-analysis/