ArticleArthritis research & therapy2021
Multiomic study of skin, peripheral blood, and serum: is serum proteome a reflection of disease process at the end-organ level in systemic sclerosis?
Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Peripheral Blood Gene Expression Profiling and Prognostic Significance for the Course of Interstitial Lung Disease in Patients With Systemic Sclerosis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Trial
- Gain of function NOTCH4 variants disrupt angiogenesis in systemic sclerosis.Annals of the rheumatic diseases · 2026Article
- Article
- Lebrikizumab Rapidly Lowers Inflammatory Biomarkers with Clinical Correlations in Moderate-to-Severe Atopic Dermatitis.Dermatology and therapy · 2025Article
- Systemic Sclerosis Dermal Fibroblast Exosomes Trigger Type 1 Interferon Responses in Keratinocytes via a TBK/JAK/STAT Signaling Axis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Immune Profiling of Patients with Systemic Sclerosis through Targeted Proteomic Analysis.International journal of molecular sciences · 2023Article
- The Role of Autophagy and Apoptosis in Affected Skin and Lungs in Patients with Systemic Sclerosis.International journal of molecular sciences · 2023Review
- Distinct genome-wide DNA methylation and gene expression signatures in classical monocytes from African American patients with systemic sclerosis.Clinical epigenetics · 2023Article
- Proteomic aptamer analysis reveals serum markers that characterize preclinical systemic sclerosis (SSc) patients at risk for progression toward definite SSc.Arthritis research & therapy · 2023Article
- Distinct molecular subtypes of systemic sclerosis and gene signature with diagnostic capability.Frontiers in immunology · 2023Article
- Integrated analysis of dermal blister fluid proteomics and genome-wide skin gene expression in systemic sclerosis: an observational study.The Lancet. Rheumatology · 2022Article
- Peripheral blood gene expression profiling shows predictive significance for response to mycophenolate in systemic sclerosis-related interstitial lung disease.Annals of the rheumatic diseases · 2022Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
backgroundSerum proteins can be readily assessed during routine clinical care. However, it is unclear to what extent serum proteins reflect the molecular dysregulations of peripheral blood cells (PBCs) or affected end-organs in systemic sclerosis (SSc). We conducted a multiomic comparative analysis of SSc serum profile, PBC, and skin gene expression in concurrently collected samples.
methodsGlobal gene expression profiling was carried out in skin and PBC samples obtained from 49 SSc patients enrolled in the GENISOS observational cohort and 25 unaffected controls. Levels of 911 proteins were determined by Olink Proximity Extension Assay in concurrently collected serum samples.
resultsBoth SSc PBC and skin transcriptomes showed a prominent type I interferon signature. The examination of SSc serum profile revealed an upregulation of proteins involved in pro-fibrotic homing and extravasation, as well as extracellular matrix components/modulators. Notably, several soluble receptor proteins such as EGFR, ERBB2, ERBB3, VEGFR2, TGFBR3, and PDGF-Rα were downregulated. Thirty-nine proteins correlated with severity of SSc skin disease. The differential expression of serum protein in SSc vs. control comparison significantly correlated with the differential expression of corresponding transcripts in skin but not in PBCs. Moreover, the differentially expressed serum proteins were significantly more connected to the Well-Associated-Proteins in the skin than PBC gene expression dataset. The assessment of the concordance of between-sample similarities revealed that the molecular profile of serum proteins and skin gene expression data were significantly concordant in patients with SSc but not in healthy controls.
conclusionsSSc serum protein profile shows an upregulation of profibrotic cytokines and a downregulation of soluble EGF and other key receptors. Our multilevel comparative analysis indicates that the serum protein profile in SSc correlates more closely with molecular dysregulations of skin than PBCs and might serve as a reflection of disease severity at the end-organ level.
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