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

Abstract

BackgroundAnkylosing 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 MethodsAnkylosing 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.ResultsLiquid 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.ConclusionThe 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.

Quantitative proteomic screening uncovers candidate diagnostic and monitoring serum biomarkers of ankylosing spondylitis

“…Our study is the first to use aptamer-based high-throughput technology to capture low-abundance serum proteins in AS patients and controls, identifying DEP new potential biomarkers for diagnosis and disease activity in addition to confirming previous findings. For example, among our top diagnosis DEPs, SAA1 has now been shown in multiple studies to be elevated in AS while Trefoil Factor (TFF)1 has not been reported in AS/AxSpA [ 10 – 12 ].…”

“…Large-scale examination of proteins, unlike DNA and RNA, remains scarce and limited in AS. Recent mass spectrometry-based studies of AS patients compared to healthy controls have revealed dysregulation of serum proteins—including complement, metalloproteinases, and serum amyloid A1 (SAA1) [ 10 – 12 ]. Dynamic range limitations of this lab technique however limit proteome coverage, which may restrict molecular characterization of AS [ 13 ].…”

Tandem mass tag (TMT) quantitative protein analysis‐based proteomics and parallel reaction monitoring (PRM) validation revealed that MST4 accelerates osteosarcoma proliferation by increasing MRC2 activity

“…PRM validation was performed on differentially expressed proteins to validate the TMT‐based proteomic analysis results by LC–MS/MS 15 . A total of 25 proteins were analyzed.…”

“…PRM validation was performed on differentially expressed proteins to validate the TMT-based proteomic analysis results by LC-MS/MS. 15 Proteome Discoverer (v. 2.1) and Skyline (v. 3.6) were used for raw MS data processing. The MASCOT engine was applied to search the list of derived peaks based on the UniProt Homo sapiens protein database in Proteome Discoverer.…”

Human peripheral blood mononuclear cells as a valuable source of disease‐related biomarkers: Evidence from comparative proteomics studies

“…These proteins are produced solely in plasmacytoid dendritic cells. Here are also ITPR1 as biomarker for diagnosis of Ankylosing spondylitis [43], and IGKC as biomarker for antiretroviral therapy outcome in HIV-positive patients [65] that have at least four times higher expression in memory B-cell/naive B-cell than in any blood cell type. CLEC4D and ELANE as biomarkers for Sepsis [62] Biomarker that can distinguish between early-and late-Amyotrophic lateral sclerosis [6]; Biomarker for detection of sporadic form of Amyotrophic lateral sclerosis [24] Biomarkers involved in RNA metabolism defects caused by the FXS pathology [35]; Biomarker for Systemic lupus erythematosus [48] PPIA Peptidyl-prolyl cis-trans isomerase A Low immune cell specificity Detected in all Low lineage specificity Detected in all Biomarker that can distinguish between early-and late-Amyotrophic lateral sclerosis [6]; Biomarker for detection of sporadic form of Amyotrophic lateral sclerosis [24] Biomarker for early diagnosis of Ankylosing spondylitis [42]; Biomarker for the co-pathogenesis of tuberculosis and diabetes [68]; Biomarker for Schizophrenia [40] TARDBP TAR DNA-binding protein 43 Low immune cell specificity Detected in all Low lineage specificity Detected in all Biomarker for detection of sporadic form of Amyotrophic lateral sclerosis [24] Biomarker that can distinguish between early-and late-Amyotrophic lateral sclerosis [ Detected in all Biomarker for Sepsis [62] Biomarker for Sepsis [ *The RNA expression profiles of human protein-coding genes in 18 immune cell types covering various B-cells, T-cells, NK-cells, monocytes, granulocytes and dendritic cells are according to the data from Human Protein Atlas (HPA).…”