Abstract
Primary Sjögren syndrome (pSS) is a common autoimmune disease. Here, we performed the first proteome and phosphoproteome analyses of peripheral blood mononuclear cells in pSS patients to obtain a comprehensive profile and identify the potential crucial proteins and pathways for the screening and evaluation of pSS patients. Peripheral blood mononuclear cells from 8 pSS-confirmed patients (American-European Consensus Group Criteria, 2002) and 10 normal controls were selected. Label-free quantitative proteomics was utilized to obtain quantitative information. In total, 787 proteins were identified as differentially expressed proteins, and 175 phosphosites on 123 proteins were identified as differentially phosphorylated proteins. We performed functional enrichment analyses with these proteins and phosphoproteins based on public database. Furthermore, protein-protein interaction network analyses were performed by using multiple algorithms. Using module and hub protein analyses, we identified 16 modules for the proteins, 2 clusters for the phosphoproteins and selected the top 10 hub proteins. Finally, we identified 22 motifs using motif analysis of the phosphosites and found 17 newly identified motifs, while 6 motifs were experimentally verified for known protein kinases. The findings distinguished pSS patients from normal controls at the peripheral blood mononuclear cells level and revealed potential candidates for use in pSS diagnosis.
Highlights
Primary Sjögren syndrome is a chronic autoimmune disease with lymphocytic infiltration and epithelial cell destruction but no association with other autoimmune diseases [1]
Based on a shotgun proteomics approach, 2517 proteins were identified in the study based on 12692 unique peptides and a maximum false positive rate (FDR) < 1%, among which 1111 proteins were at a quantifiable level in the Primary Sjögren syndrome (pSS) or normal controls (NC)-pSS groups (Supplementary Table 1)
Based on proteome and phosphoproteome analyses, our results provide new insights into pSS and reveal many essential features of and differences in the peripheral blood mononuclear cells (PBMCs) of pSS through a systematic bioinformatics analysis
Summary
Primary Sjögren syndrome (pSS) is a chronic autoimmune disease with lymphocytic infiltration and epithelial cell destruction but no association with other autoimmune diseases (e.g., scleroderma, systemic lupus erythematosus or rheumatoid arthritis) [1]. It often invades the salivary gland and lacrimal gland, where it manifests as xerostomia of the mouth and eyes [1], which might severely decrease patients’ quality of life. Patients with visceral www.aging-us.com damage mostly achieve remission after proper treatment, but they can relapse after treatment withdrawal [4]. With an overall prevalence of 0.1-0.6% in the adult population [5], nearly 0.1% in Europe [6] and 0.33-0.77% in China [7], no disease-modifying drug is currently available for the disease, and the current treatment for pSS focuses only on relieving symptoms, which is unsatisfactory [8]
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