S100A6, Calumenin and Cytohesin 2 as Biomarkers for Cutaneous Involvement in Systemic Sclerosis Patients: A Case Control Study

Bălănescu, Paul; Bălănescu, Eugenia; Băicuș, Cristian; Balanescu, A.

doi:10.3390/jpm11050368

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…S100A6 interacts with a wide range of protein ligands, some of which are related to immunological response (Filipek & Lesniak, 2018), including RAGE (Filipek & Lesniak, 2018; Xie et al., 2013). S100A6 has been shown to be increased in the serum of patients with systemic sclerosis, and this has been correlated with disease activity (Balanescu et al., 2021). Integrin, a transmembrane receptor that facilitates cell–cell and cell–extracellular matrix adhesion, has also been shown to interact with S100A6 (Jurewicz et al., 2014).…”

Section: Discussionmentioning

confidence: 99%

S100A6 participates in initiation of autoimmune encephalitis and is under epigenetic control

Lin

et al. 2023

Brain and Behavior

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Introduction: Autoimmune encephalitis (AE) is caused by autoantibodies attacking neuronal cell surface antigens and/or synaptic antigens. We previously demonstrated that S100A6 was hypomethylated in patients with AE and that it promoted B lymphocyte infiltration through the simulated blood-brain barrier (BBB). In this study, we focused on the epigenetic regulation of S100A6, the process by which S100A6 affects B lymphocyte infiltration, and the therapeutic potential of S100A6 antibodies. Methods:We enrolled and collected serum from 10 patients with AE and 10 healthy control (HC) subjects. Promoter methylation and 5-azacytidine treatment assays were conducted to observe the methylation process of S100A6. The effect of S100A6 on B lymphocytes was analyzed using an adhesion assay and leukocyte transendothelial migration (LTEM) assay. A LTEM assay was also used to compare the effects of the serum of HCs, serum of AE patients, S100A6 recombinant protein, and S100A6 antibodies on B lymphocytes. Result:The promoter methylation and 5-azacytidine treatment assays confirmed that S100A6 was regulated by DNA methylation. The adhesion study demonstrated that the addition of S100A6 enhanced adhesion between B lymphocytes and a BBB endothelial cell line in a concentration-dependent manner. The LTEM assay showed that the serum of AE patients, as well as S100A6, promoted B lymphocyte infiltration and that this effect could be attenuated by S100A6 antibodies. Conclusion:We clarified that S100A6 was under epigenetic regulation in patients with AE and that it helped B lymphocytes to adhere to and infiltrate the BBB endothelial layer, which could be counteracted by S100A6 antibodies. Therefore, the methylation [Correction added on 15th February 2023, after first online publication: equal contributions of Chih-Hsiang Lin and Sung-Chou Li has been added]This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Discussionmentioning

confidence: 99%

S100A6 participates in initiation of autoimmune encephalitis and is under epigenetic control

Lin

et al. 2023

Brain and Behavior

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“…In this study, serum samples from the already available Ssc biobank of the Internal Medicine Clinic of Colentina Clinical Hospital were used. Data about the inclusion of samples in the biobank, evaluation of the included patients and descriptive data of patients are detailed elsewhere ( 12 ). Briefly, the Ssc biobank includes samples of 53 Ssc patients (4 males/49 females, median age 56 (25-81) years) and 26 healthy age and gender matched controls (2 males/24 females, median age 52 (26-63) years).…”

Section: Methodsmentioning

confidence: 99%

Circulatory cytokeratin 17, marginal zone B1 protein and leucine-rich α2-glycoprotein-1 as biomarkers for disease severity and fibrosis in systemic sclerosis patients

Bălănescu¹,

Bălănescu²,

Băicuș³

et al. 2022

Biochem. med. (Online)

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IntroductionSystemic sclerosis (Ssc) is a multiorgan debilitating autoimmune disease that associates the triad: vascular involvement, tissue fibrosis and profound immune response alterations. Numerous previous studies focused on identification of candidate proteomic Ssc biomarkers using mass-spectrometry techniques and a large number of candidate Ssc biomarkers emerged. These biomarkers must firstly be confirmed in independent patient groups. The aim of the present study was to investigate the association of cytokeratin 17 (CK17), marginal zone B1 protein (MZB1) and leucine-rich α2-glycoprotein-1 (LRG1) with clinical and biological Ssc characteristics. Material and methodsSerum CK17, MZB1 and LRG1 were assessed in samples of the available Ssc biobank comprising of samples from 53 Ssc patients and 26 matched age and gender controls. ResultsCirculatory CK17, LRG1 and MZB1 concentrations were increased in Ssc patients. Cytokeratin 17 is independently associated with Ssc disease activity. Patients with pulmonary fibrosis expressed higher LRG1 and MZB1 concentrations. Serum MZB1 concentrations were also associated with extensive skin fibrosis. ConclusionsSerum CK17, MZB1 and LRG1 were confirmed biomarkers for Ssc. LRG1 seems a good biomarker for pulmonary fibrosis, while MZB1 is a good biomarker for extensive skin fibrosis. CK17 proved to be independently associated with Ssc disease severity, higher CK17 values being protective for a more active disease.

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“…S100A6 has similar functions in other diseases. Serum calumin, S100A6, and cytokinin 2 have been confirmed as biomarkers in patients with systemic sclerosis with skin involvement, and S100A6 is related to the number of active digital ulcers [ 124 ]. Another study used a functional proteomic approach to analyze bronchoalveolar lavage samples from patients with pulmonary fibrosis systemic sclerosis (PF-SSc), smokers, and nonsmokers.…”

Section: Biomarker Role Of S100a6mentioning

confidence: 99%

S100A6: molecular function and biomarker role

Wang,

Kang,

Kang

et al. 2023

Biomark Res

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S100A6 (also called calcyclin) is a Ca2+-binding protein that belongs to the S100 protein family. S100A6 has many functions related to the cytoskeleton, cell stress, proliferation, and differentiation. S100A6 also has many interacting proteins that are distributed in the cytoplasm, nucleus, cell membrane, and outside the cell. Almost all these proteins interact with S100A6 in a Ca2+-dependent manner, and some also have specific motifs responsible for binding to S100A6. The expression of S100A6 is regulated by several transcription factors (such as c-Myc, P53, NF-κB, USF, Nrf2, etc.). The expression level depends on the specific cell type and the transcription factors activated in specific physical and chemical environments, and is also related to histone acetylation, DNA methylation, and other epigenetic modifications. The differential expression of S100A6 in various diseases, and at different stages of those diseases, makes it a good biomarker for differential diagnosis and prognosis evaluation, as well as a potential therapeutic target. In this review, we mainly focus on the S100A6 ligand and its transcriptional regulation, molecular function (cytoskeleton, cell stress, cell differentiation), and role as a biomarker in human disease and stem cells.

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S100A6, Calumenin and Cytohesin 2 as Biomarkers for Cutaneous Involvement in Systemic Sclerosis Patients: A Case Control Study

Cited by 6 publications

References 25 publications

S100A6 participates in initiation of autoimmune encephalitis and is under epigenetic control

S100A6 participates in initiation of autoimmune encephalitis and is under epigenetic control

Circulatory cytokeratin 17, marginal zone B1 protein and leucine-rich α2-glycoprotein-1 as biomarkers for disease severity and fibrosis in systemic sclerosis patients

S100A6: molecular function and biomarker role

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