Proteomic profiling of saliva reveals association of complement system with primary Sjögren's syndrome

Li, Mingde; Qi, Yinghua; Wang, Guizhen; Bu, Su; Chen, Ming; Yu, Jin; Luo, Tianyang; Meng, Lulu; Dai, Anran; Yong, Zhou; Liu, Shuai; Huo, Xingxing

doi:10.1002/iid3.529

Cited by 8 publications

(5 citation statements)

References 33 publications

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“…Proteomic analysis using an experimental SS mouse model revealed that salivary C3, complement factor H (CFH), serpin family G member 1 (SERPING1), fibrinogen alpha (FGA), and fibrinogen gamma (FGG) expressions were different between SS model and control mice [ 26 ]. Downregulation of salivary C3, CFH, SERPING1, FGA, FGG is associated with activation of the alternative complement system and defects in the complement system with low production of complement proteins.…”

Section: Proteomic Analysismentioning

confidence: 99%

“…Immune complex formation and deposition are critical in the pathogenesis of autoimmune disease, including SS, and the presence of immune complexes in the serum, blood vessels, and glomeruli has been found in patients with SS. Proteomic analysis using immune complex-capturing beads and nano-LC-MS/MS identified 998 immune complex-antigen present in the saliva of nine patients with SS, but not in the saliva of seven non-SS patients [ 26 ]. Neutrophil defensin 1 and small proline-rich protein 2D were found most frequently in patients with SS.…”

Section: Proteomic Analysismentioning

confidence: 99%

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Salivary Biomarkers in Patients with Sjögren’s Syndrome—A Systematic Review

Jung

Kim

et al. 2021

IJMS

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Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by dry mouth and dry eyes, with lymphocytic infiltration of the exocrine glands. Saliva is becoming a useful tool to determine the clinical and pathological characteristics of SS because the collection method is easy and non-invasive. Since 1900, salivary proteomic analysis has been performed continuously using a variety of optimized analytical methods. Many studies have identified distinct characteristics of salivary proteins in patients with primary SS, and the changes were related to chronic inflammation and overproduction of immunoglobulins or downregulated secretory function. Several proteomic studies using whole or parotid saliva have evaluated whether several salivary proteins can be used to discriminate SS, including salivary β2-microglobulin, calprotectin, carbonic anhydrase VI, neutrophil gelatinase-associated lipocalin, sialic acid-binding immunoglobulin-like lectin-5, and tripartite motif-containing protein 29. In addition, salivary proinflammatory cytokine levels have been reported to be increased in patients with SS. Although these candidate salivary proteins have exhibited considerable differences in patients with SS, more data are needed to confirm their role as biomarkers. Moreover, the identification of salivary characteristics that can accurately reflect disease activity, predict treatment response and prognosis, and diagnose SS is anticipated.

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Section: Proteomic Analysismentioning

confidence: 99%

Section: Proteomic Analysismentioning

confidence: 99%

Salivary Biomarkers in Patients with Sjögren’s Syndrome—A Systematic Review

Jung

Kim

et al. 2021

IJMS

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“…In an experimental murine model, proteomics has recently showed a differential expression of C3 and complement factor H, together with Serpin family G member 1 (SERPING1), fibrinogen α and γ, in the saliva of SjS mice compared to controls ( Li et al, 2021 ). Patients diagnosed with SjS can present hypocomplementemia, in rates ranging between 2 and 25% for C3, 10–39.5% for C4 and 14–15% for CH50 ( Skopouli et al, 2000 ; Ioannidis et al, 2002 ; Theander et al, 2004 ; Ramos-Casals et al, 2005 ; Brito-Zerón et al, 2012 ; Brito-Zerón et al, 2018 ; Anquetil et al, 2019 ; Sebastian et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Beyond Systemic Lupus Erythematosus and Anti-Phospholipid Syndrome: The Relevance of Complement From Pathogenesis to Pregnancy Outcome in Other Systemic Rheumatologic Diseases

et al. 2022

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Evidence about the relevance of the complement system, a highly conserved constituent of the innate immunity response that orchestrates the elimination of pathogens and the inflammatory processes, has been recently accumulated in many different rheumatologic conditions. In rheumatoid arthritis, complement, mainly the classical pathway, contributes to tissue damage especially in seropositive subjects, with complement activation occurring in the joint. Data about complement pathways in psoriatic arthritis are dated and poorly consistent; among patients with Sjögren syndrome, hypocomplementemia exerts a prognostic role, identifying patients at risk of extra-glandular manifestations. Hints about complement involvement in systemic sclerosis have been recently raised, following the evidence of complement deposition in affected skin and in renal samples from patients with scleroderma renal crisis. In vasculitides, complement plays a dual role: on one hand, stimulation of neutrophils with anti-neutrophil cytoplasmic antibodies (ANCA) results in the activation of the alternative pathway, on the other, C5a induces translocation of ANCA antigens, favouring the detrimental role of antibodies. Complement deposition in the kidneys identifies patients with more aggressive renal disease; patients with active disease display low serum levels of C3 and C4. Even though in dermatomyositis sC5b-9 deposits are invariably present in affected muscles, data on C3 and C4 fluctuation during disease course are scarce. C3 and C1q serum levels have been explored as potential markers of disease activity in Takayasu arteritis, whereas data in Behçet disease are limited to in vitro observations. Pregnancies in women with rheumatologic conditions are still burdened by a higher rate of pregnancy complications, thus the early identification of women at risk would be invaluable. A fine-tuning of complement activation is required from a physiological progression of pregnancy, from pre-implantation stages, through placentation to labour. Complement deregulation has been implicated in several pregnancy complications, such as recurrent abortion, eclampsia and premature birth; low complement levels have been shown to reliably identify women at risk of complications. Given its physiologic role in orchestrating pregnancy progression and its involvement as pathogenic effector in several rheumatologic conditions, complement system is an attractive candidate biomarker to stratify the obstetric risk among women with rheumatologic conditions.

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“…However, immunological differences exist between humans and mice (8,9). Through literature review and previous research of the research group, C57BL/6 mice are found to be a typical animal model of antigen induced SS (10)(11)(12). We performed immune infiltration analyses of the pSS human salivary gland (SG) CIBERSORT (13) and pSS C57BL/6 mouse seq-ImmuCC models.…”

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confidence: 99%

Immune infiltration analysis reveals immune cell signatures in salivary gland tissue of primary Sjögren’s syndrome

Gong

Qiu

et al. 2023

Front. Med.

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IntroductionMouse models are the basis for primary Sjögren’s syndrome (pSS) research. However, the depth of comparisons between mice and humans in salivary gland (SG) immune cells remains limited.MethodsThe gene expression profiles of SGs from normal subjects and pSS patients were downloaded from the Gene Expression Comprehensive Database. The proportion of infiltrating immune cell subsets was then assessed by cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT). An experimental Sjögren’s syndrome (ESS) mouse model was successfully constructed using SG protein. Based on mouse SG tissue RNA-Seq data, the seq-ImmuCC model was used to quantitatively analyze the compositional ratios of 10 immune cells in pSS patients and mouse model SG tissues.ResultsComputed and obtained 31 human data samples using the CIBERSORT deconvolution method. The immune cell infiltration results showed that, compared to normal human SG tissue, the content of gamma delta T cells was significantly different from naive CD4+ T cells and significantly increased, while the plasma cell content decreased. Principal component analysis indicated differences in immune cell infiltration between pSS patients and normal subjects. Meanwhile, for ESS model mouse data analysis, we found that the proportion of macrophages increased, while the proportion of CD4+ T cells, B cells, and monocytes decreased. Furthermore, we found that the proportion of monocytes was decreased, while the proportion of macrophages was increased in the SG tissues of pSS patients and model mice. The infiltration of CD4+ T, CD8+ T, and B cells also showed some differences.DiscussionWe comprehensively analyzed SG immune infiltration in pSS patients and model mice. We demonstrated conserved and nonconserved aspects of the immune system in mice and humans at the level of immune cells to help explain the primary regulation of immune mechanisms during the development of Sjögren’s syndrome.

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Proteomic profiling of saliva reveals association of complement system with primary Sjögren's syndrome

Cited by 8 publications

References 33 publications

Salivary Biomarkers in Patients with Sjögren’s Syndrome—A Systematic Review

Salivary Biomarkers in Patients with Sjögren’s Syndrome—A Systematic Review

Beyond Systemic Lupus Erythematosus and Anti-Phospholipid Syndrome: The Relevance of Complement From Pathogenesis to Pregnancy Outcome in Other Systemic Rheumatologic Diseases

Immune infiltration analysis reveals immune cell signatures in salivary gland tissue of primary Sjögren’s syndrome

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