Research Paper Volume 13, Issue 1 pp 1071—1095

Integrated proteome and phosphoproteome analyses of peripheral blood mononuclear cells in primary Sjögren syndrome patients

Shaoying Huang1, , Fengping Zheng1, , Lixiong Liu2, , Shuhui Meng1, , Wanxia Cai1, , Cantong Zhang1, , Weier Dai4, , Dongzhou Liu2, , Xiaoping Hong2, , Donge Tang1, , Yong Dai1,3, ,

  • 1 Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen People’s Hospital, The First Affiliated Hospital Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen 518020, Guangdong, China
  • 2 Department of Rheumatology and Immunology, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People’s Hospital, Shenzhen 518020, Guangdong, China
  • 3 Guangxi Key Laboratory of Metabolic Disease Research, Nephrology Department of Guilin, Guilin 541002, China
  • 4 College of Natural Science, University of Texas at Austin, Austin, TX 78712, USA

Received: June 18, 2020       Accepted: October 27, 2020       Published: December 3, 2020      

https://doi.org/10.18632/aging.202233
How to Cite

Copyright: © 2020 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

pSS: primary Sjögren syndrome; AECG: American-European classification criteria; PBMCs: peripheral blood mononuclear cells; NK: natural killer; DEPs: differentially expressed proteins; DPPs: differentially phosphorylated proteins; IMAC: immobilized metal affinity chromatography; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; PPI: protein-protein interaction; NC: normal control; PASEF: parallel cumulative serial fragmentation; FDR: false positive rate; MCODE: molecular complex detection; ARVC: arrhythmogenic right ventricular cardiomyopathy; HCM: hypertrophic cardiomyopathy; PKs: protein kinases; pS: phospho-serine; pT: phospho-threonine; HPRD: Human Protein Reference Database; CKII: casein kinase II.