DNA Methylation-Based Interferon Scores Associate With Sub-Phenotypes in Primary Sjögren’s Syndrome

Imgenberg‐Kreuz, Juliana; Sandling, Johanna K.; Norheim, Katrine Brække; Johnsen, Svein Joar Auglænd; Omdal, Roald; Syvänen, Ann‐Christine; Svenungsson, Elisabet; Rönnblom, Lars; Eloranta, Maija‐Leena; Nordmark, Gunnel

doi:10.3389/fimmu.2021.702037

Cited by 17 publications

(18 citation statements)

References 42 publications

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“…Studies showed that IFIT1 and IFI44L were associated with the overactivation of the type I IFN in pSS, which was of great value in guiding treatment decisions, monitoring and patient strati cation [14,15]. As the ligand of chemokine receptor CXCR3, CXCL9 was induced by IFN γ and mainly acted on monocytes/macrophages and lymphocytes, mediating in ammatory responses [16,17].…”

Section: Discussionmentioning

confidence: 99%

Uncovering potential new biomarkers and immune infiltration characteristics in primary Sojgren's syndrome by integrated bioinformatics analysis

Zhang

Bao

et al. 2022

Preprint

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Background: Primary Sojgren's syndrome (pSS) is known as autoimmune disease of endocrine system. This study aimed to identify potential biomarkers for pSS using integrated bioinformatics analysis and explore the relationship between differentially expressed genes (DEGs) and immune infiltration. Methods: Three pSS datasets (GSE7451, GSE23117 and GSE40611) from the Gene Expression Omnibus (GEO) database were integrated. All the datasets were processed by affy in R (version 4.0.3).Results: A total of 16 immune cells and 13 immune functions infiltration scores were obtained. The top immune cell and immune function were "activated" dendritic cells (aDCs) and major histocompatibility complex (MHC) class I. Correlation analysis showed the top correlation among 16 immune cells were B cells and tumor infiltrating lymphocytes (TIL), check-point and T cell co-stimulation, respectively. In comparisons of immune score, aDCs (0.657 vs 0.594, P < 0.001), B cells (0.492 vs 0.434, P = 0.004), macrophages (0.631 vs 0.601, P = 0.010), inflammation-promoting (0.545 vs 0.478, P < 0.001), Type I interferon (IFN) Reponse (0.728 vs 0.625, P < 0.001) and so on were higher in pSS than control group. In correlation analysis, the up-regulation of IFIT1 gene was strongly correlated with Type I IFN Reponse with a correlation coefficient of 0.87. The ROC curve of 5 genes showed that the area under curve (AUC) was 0.891. In the verification model, the AUC was 0.881. In addition, DO analysis supported the association between DEGs and pSS. Conclusions: In summary, pSS has a variety of DEGs in immune infiltration, which is worthy of the attention from clinicians.

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Section: Discussionmentioning

confidence: 99%

Uncovering potential new biomarkers and immune infiltration characteristics in primary Sojgren's syndrome by integrated bioinformatics analysis

Zhang

Bao

et al. 2022

Preprint

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“…DNA methylation‐based IFN scores associate with sub‐phenotypes in primary Sjögren's syndrome 46 . The DNA methylation‐based IFN score is thus a promising alternative to mRNA‐based scores for identification of patients with activation of the IFN system and may be applied for patient stratification guiding treatment decisions, monitoring, and inclusion in clinical trials 46 …”

Section: Focal Inflammation With Mixed Cellular Compositionmentioning

confidence: 99%

“…45 DNA methylation-based IFN scores associate with subphenotypes in primary Sjögren's syndrome. 46 The DNA methylation-based IFN score is thus a promising alternative to mRNA-based scores for identification of patients with activation of the IFN system and may be applied for patient stratification guiding treatment decisions, monitoring, and inclusion in clinical trials. 46 As already alluded to, a minor salivary gland biopsy with focal lymphocytic sialadenitis and a focus score of ≥1 is the currently accepted pathological finding confirming the exocrinopathy of Sjögren's syndrome.…”

Section: With Mixed Cellular Compositionmentioning

confidence: 99%

“…46 The DNA methylation-based IFN score is thus a promising alternative to mRNA-based scores for identification of patients with activation of the IFN system and may be applied for patient stratification guiding treatment decisions, monitoring, and inclusion in clinical trials. 46 As already alluded to, a minor salivary gland biopsy with focal lymphocytic sialadenitis and a focus score of ≥1 is the currently accepted pathological finding confirming the exocrinopathy of Sjögren's syndrome. 31,33 However, adipocytes can occupy a large percentage of the glandular area although little is known about their significance in Sjögren's lesions.…”

Section: With Mixed Cellular Compositionmentioning

confidence: 99%

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Disease mechanisms in Sjögren’s syndrome: What do we know?

Jönsson

2022

Scand J Immunol

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Why should we explore and study disease mechanisms? This is particularly important when we are dealing with complex pathogenesis without a direct causal agent, for example, syndromes with multiple organ involvements. Sjögren's syndrome is definitely such an entity. Also, there are a number of reasons for such studies such as disclosing the aetiology, to identify biomarkers for diagnosis and assessment of the disease process and monitor response to treatment, to determine targets for treatment, to define critical items in classification criteria, amongst others. Samples available for the study of disease mechanisms in Sjögren's syndrome have included serum (autoantibodies, cytokines), DNA (gene profiling, GWAS), cells (phenotypes/flow cytometry, proportion of cells/CyTOF), tissue (focal inflammation, germinal centres, mass cytometry), and saliva (proteomics, biochemistry, mucosal immunity). An original explanatory concept for the pathogenesis of Sjögren's syndrome proposed a specific and self‐perpetuating immune‐mediated loss of exocrine tissue as the principal cause of glandular hypofunction. This hypothesis however falls short of accommodating several Sjögren's syndrome‐related phenomena and experimental findings. Today, the emergence of advanced bio‐analytical platforms has further enabled the identification of central pathogenic processes and potential biomarkers. The purpose of this minor review is to highlight a selection of previous but also recent and novel aspects on the disease mechanisms in Sjögren's syndrome.

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“…DNA methylation is a well-studied epigenetic modi cations that regulates gene expression 8 . So far, a number of studies have provided evidence of aberrant DNA methylation pro les in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and sjogren's syndrome (SS) patients 9,10,11,12,13,14,15,16,17,18 . The DNA methylation changes in IgG4-RD patients are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Differential CpG DNA Methylation of Peripheral B, CD4 + T cells and Salivary Gland Tissues in IgG4-related Disease

Wang

et al. 2022

Preprint

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Objectives. Immunoglobulin-G4-related disease (IgG4-RD) is a distinct systemic autoimmune-mediated disease that characterized by tissue fibrosis. The purpose of this study is to investigate the epigenetic modifications in IgG4-RD. Methods. A genome-wide DNA methylation study was performed in B cells, CD4+ T cells and salivary gland tissue from IgG4-RD patients and matched controls using the Illumina HumanMethylation 850K BeadChip. Results. We identified differentially methylated CpG sites including 44 hypomethylated and 166 hypermethylated differentially methylated probes (DMPs) in B cells, 260 hypomethylated and 260 hypermethylated DMPs in CD4 + T cells from 10 IgG4-RD patients compared with 10 healthy controls. We also identified 36945 hypomethylated and 78380 hypermethylated DMPs in salivary gland tissue of 4 IgG4-RD patients compared with 4 controls. We found that DPM2 (cg21181453), IQCK (cg10266221), ABCC13 (cg05699681, cg04985582) were hypermethylated and MBP (cg18455083) was hypomethylated in B cells, CD4+ T cells and tissue of IgG4-RD patients compared with controls. Also, we observed hypomethylated HLA class in both B cells and CD4+ T cells from IgG4-RD patients compared with controls. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DMPs in salivary gland of IgG4-RD patients demonstrated enrichment of pathways in regulation of immune cells responses and fibrosis. Conclusion. Our study is the first DNA methylation study in peripheral B cells, CD4+ T cells as well as salivary gland tissues from patients with IgG4-related disease. Our findings highlighted the role of epigenetic modification of DNA methylation and identified several genes and pathways that might involve in the pathogenesis of IgG4-RD.

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DNA Methylation-Based Interferon Scores Associate With Sub-Phenotypes in Primary Sjögren’s Syndrome

Cited by 17 publications

References 42 publications

Uncovering potential new biomarkers and immune infiltration characteristics in primary Sojgren's syndrome by integrated bioinformatics analysis

Uncovering potential new biomarkers and immune infiltration characteristics in primary Sojgren's syndrome by integrated bioinformatics analysis

Disease mechanisms in Sjögren’s syndrome: What do we know?

Differential CpG DNA Methylation of Peripheral B, CD4 + T cells and Salivary Gland Tissues in IgG4-related Disease

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