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. 2020 Aug 3;5(32):20153-20161.
doi: 10.1021/acsomega.0c01776. eCollection 2020 Aug 18.

Quantitative Proteomic Analyses To Reveal the Key Features of Proteins in New Onset Ankylosing Spondylitis Patients

Yong-Ping Lu  1   2 , Xiao-Li Zhang  2 , Fengping Zheng  3 , Chen Yun  4 , Chengxin Zhu  3 , Wanxia Cai  3 , Dongzhou Liu  3 , Xiaoping Hong  3 , Qiang Li  5 , Bo Hu  1 , Donge Tang  3 , Liang-Hong Yin  1 , Yong Dai  3
Affiliations

Quantitative Proteomic Analyses To Reveal the Key Features of Proteins in New Onset Ankylosing Spondylitis Patients

Yong-Ping Lu et al. ACS Omega. .

Abstract

Ankylosing spondylitis (AS) is a chronic immune-mediated disease. Various immune cells play an essential role in the AS pathogenesis. However, the specific pathogenesis of AS has not been well understood. Proteomic profiles of peripheral blood mononuclear cells (PBMCs) were applied to reveal the specific pathogenesis of AS. Quantitative proteomic analyses were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based methods to investigate the protein profiling of PBMCs from new-onset AS patients (n = 9) and healthy controls (n = 9). We identified 782 differentially expressed proteins (DEPs) and 527 differentially phosphorylated proteins (DPPs) between AS patients and healthy controls. The subcellular location of DEPs and DPPs showed that most of the DEPs were from the cytoplasm (n = 296, 38%), were extracellular (n = 141, 18%), and from the nucleus (n = 114, 15%); most of the DPPs were from the cytoplasm (n = 37, 34%), nucleus (n = 35, 32%), and plasma membrane (n = 10, 9%). We further identified 89 proteins with both expression and phosphorylation differences. The functional annotation of the 89 differentially expressed and phosphorylated proteins enriched in the antigen processing and presentation pathway. Four DEPs with six phosphorylated positions were found in the antigen processing and presentation pathway. The differentially expressed and phosphorylated proteins may be helpful to uncover the pathogenesis of AS. The six AS-specific proteins may serve as candidate markers for AS diagnosis and new treatment targets.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Protein identification. (a,b) DEPs and DPPs between AS patients and healthy controls, respectively. (c,d) Hierarchical clustering analysis of DEPs and DPPs, respectively. The color bar indicates fold-change of proteins between AS patients and healthy controls. Purple indicates downregulated proteins, and yellow indicates upregulated proteins. (e) Venn diagram between DEPs and DPPs. DEPs, differentially expressed proteins; DPPs, differentially phosphorylated proteins; AS, ankylosing spondylitis; HC, healthy controls.
Figure 2
Figure 2
Functional characterization and functional enrichment of differentially quantified proteins. (a,b) subcellular location of DEPs and DPPs, respectively. (c,d) Functional category DEPs and DPPs in GO terms. DEPs, differentially expressed proteins; DPPs, differentially phosphorylated proteins.
Figure 3
Figure 3
GO-based enrichment analysis of DEPs (a) and DPPs (b). DEPs, differentially expressed proteins; DPPs, differentially phosphorylated proteins.
Figure 4
Figure 4
KEGG pathway-based enrichment analysis of DEPs (a) and DPPs (b). The bubble chart shows the top 20 signal pathways with the most significant enrichment. The color of the circle indicates the p-value of significant enrichment, and the size of the circle indicates the number of differential proteins in the pathway. DEPs, differentially expressed proteins; DPPs, differentially phosphorylated proteins.
Figure 5
Figure 5
Differentially quantified proteins in the antigen processing and presentation signal pathway. (a) overview of DEPs and DPPs antigen processing and presentation pathway. (b) differentially expressed and phosphorylated proteins in the antigen processing and presentation signal pathway. The left of the x-axis shows proteins or phosphorylation increased in AS patients, and the right of the x-axis shows proteins or phosphorylation increased in healthy controls; the y-axis shows the gene name. DEPs, differentially expressed proteins; DPPs, differentially phosphorylated proteins; AS, ankylosing spondylitis.
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