Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar 17:13:838891.
doi: 10.3389/fimmu.2022.838891. eCollection 2022.

Global Proteomic Analyses Reveals Abnormal Immune Regulation in Patients With New Onset Ankylosing Spondylitis

Zongchao Yu  1 , Xiaoping Hong  2 , Xiaoli Zhang  3 , Fengping Zheng  2 , Fanna Liu  1 , Huixuan Xu  2 , Chengxin Zhu  2 , Wanxia Cai  2 , Dongzhou Liu  1 , Lianghong Yin  1 , Bo Hu  1 , Donge Tang  2 , Yong Dai  2
Affiliations

Global Proteomic Analyses Reveals Abnormal Immune Regulation in Patients With New Onset Ankylosing Spondylitis

Zongchao Yu et al. Front Immunol. .

Abstract

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease with serious consequences and a high rate of morbidity and mortality, In our previous work, we reveal the key features of proteins in new-onset ankylosing spondylitis patients.

Material and methods: Ankylosing spondylitis (AS) is a chronic inflammatory condition that affects the spine, and inflammation plays an essential role in AS pathogenesis. The inflammatory process in AS, however, is still poorly understood due to its intricacy. Systematic proteomic and phosphorylation analyses of peripheral blood mononuclear cells (PBMCs) were used to investigate potential pathways involved in AS pathogenesis.

Results: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was performed and discovered 782 differentially expressed proteins (DEPs) and 122 differentially phosphorylated proteins (DPPs) between 9 new-onset AS patients and 9 healthy controls. The DEPs were further verified using parallel reaction monitoring (PRM) analysis. PRM analysis verified that 3 proteins (HSP90AB1, HSP90AA1 and HSPA8) in the antigen processing and presentation pathway, 6 proteins (including ITPR1, MYLK and STIM1) in the platelet activation pathway and 10 proteins (including MYL12A, MYL9 and ROCK2) in the leukocyte transendothelial migration pathway were highly expressed in the PBMCs of AS patients.

Conclusion: The key proteins involved in antigen processing and presentation, platelet activation and leukocyte transendothelial migration revealed abnormal immune regulation in patients with new-onset AS. These proteins might be used as candidate markers for AS diagnosis and new therapeutic targets, as well as elucidating the pathophysiology of AS.

Keywords: ankylosing spondylitis (AS); global proteomic; immune regulation; peripheral blood mononuclear cells (PBMC); phosphorylation.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Protein identification. (A, B) DEPs and DPPs between AS patients and healthy controls. DEPs, differentially expressed proteins; DPPs, differentially Phosphorylated proteins.
Figure 2
Figure 2
Enrichment analysis of phosphorylated protein motifs (A). Heatmap of the amino acid compositions of the phosphorylation sites showing the frequency of the different types of amino acids around serine (B) and threonine (C). Red indicates significant enrichment of the amino acid near the modification site, and green indicates significant reduction of the amino acid near the modification site.
Figure 3
Figure 3
COG functional classification distribution map of DEPs (A) and DPPs (B).
Figure 4
Figure 4
GO-based enrichment analysis of DEPs (A) and DPPs (B) in terms of cellular component, molecular function and biological process.
Figure 5
Figure 5
KEGG pathway-based enrichment analysis of DEPs (A) and DPPs (B).
Figure 6
Figure 6
Protein domain enrichment analysis of DEPs (A) and DPPs (B).
Figure 7
Figure 7
Protein–protein interaction (PPI) network analysis of DEPs (A) and DPPs (B). The STRING database was used to annotate the functional interactions of all the identified DEPs and DPPs.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Feltelius N, Lindh U, Venge P, Hallgren R. Ankylosing Spondylitis: A Chronic Inflammatory Disease With Iron Overload in Granulocytes and Platelets. Ann Rheum Dis (1986) 45(10):827–31. doi: 10.1136/ard.45.10.827 - DOI - PMC - PubMed
    1. Baraliakos X, Listing J, Rudwaleit M, Sieper J, Braun J. The Relationship Between Inflammation and New Bone Formation in Patients With Ankylosing Spondylitis. Arthritis Res Ther (2008) 10(5):R104. doi: 10.1186/ar2496 - DOI - PMC - PubMed
    1. Zhu J, Huang F. The Relationship Between Bone Inflammation and Structural Damage in Ankylosing Spondylitis. Zhonghua Nei Ke Za Zhi (2011) 50(2):89–91. doi: 10.3760/cma.j.issn.0578-1426.2011.02.001 - DOI - PubMed
    1. Alvarez I, Lopez de Castro JA. HLA-B27 and Immunogenetics of Spondyloarthropathies. Curr Opin Rheumatol (2000) 12(4):248–53. doi: 10.1097/00002281-200007000-00003 - DOI - PubMed
    1. Akassou A, Bakri Y. Does HLA-B27 Status Influence Ankylosing Spondylitis Phenotype? Clin Med Insights Arthritis Musculoskelet Disord (2018) 11:1179544117751627. doi: 10.1177/1179544117751627 - DOI - PMC - PubMed

Publication types