Keratin 8 is a novel autoantigen of rheumatoid arthritis

Wang, Xiaoxu; Chen, Peng; Cui, Jiawen; Yang, Chunhe; Du, Hongwu

doi:10.1016/j.bbrc.2015.07.161

Cited by 11 publications

(10 citation statements)

References 29 publications

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“…Cytoskeletal dysregulation in QUC versus C was characterized by a decrease in keratin type II cytoskeletal 8 (KRT8), actin cytoplasmic 1 (ACTB), TUBB4B, and mitochondrial inner membrane protein, whereas KRT19 increased. Several metabolic proteins were decreased, such as: SDHA, ATP synthase subunit beta (ATP5B) and short/branched chain specific acyl‐CoA dehydrogenase (ACADSB).…”

Section: Resultsmentioning

confidence: 99%

“…Given that, QUC versus C were characterized by a cytoskeletal rearrangement in which keratin 8 (which was recently described as an autoantigen in rheumatoid arthritis) is decreased, whereas other keratins (KRT10, KRT14, and KRT19) are increased, thus suggesting a structural re‐arrangement at the epithelial level. The latter can account for several pieces of evidence, indicating that physical modifications of the epithelial layers, leading to an impaired permeability and cell renewal, have a prominent role in UC pathogenesis …”

Section: Discussionmentioning

confidence: 99%

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Contribution of Extracellular Matrix and Signal Mechanotransduction to Epithelial Cell Damage in Inflammatory Bowel Disease Patients: A Proteomic Study

et al. 2017

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This study utilizes 2D-DIGE (difference gel etrophoresis), isotope-coded protein labeling and biochemical assays to characterize protein alteration in ulcerative colitis (UC) and Crohn's disease (CD) in human epithelial cell and mucosal biopsies in inflammatory bowel disease (IBD)-affected patients. The aim of this study is to identify the key molecular signatures involved in epithelial cell structure of IBDs. In non-inflamed UC (QUC) keratins, vimentin, and focal adhesion kinase (7) increased, whereas vinculin and de-tyrosinated α-tubulin decreased; inflammation (IUC) exacerbated molecular changes, being collagen type VI alpha 1 chain (COL6A1), tenascin-C and vimentin increased. In non-inflamed CD (QCD), tenascin C, de-tyrosinated α-tubulin, vinculin, FAK, and Rho-associated protein kinase 1 (ROCK1) decreased while vimentin increased. In inflamed CD (ICD), COL6A1, vimentin and integrin alpha 4 increased. In QUC, cell metabolism is characterized by a decrease of the tricarboxylic acid cycle enzymes and a decrease of short/branched chain specific acyl-CoA dehydrogenase, fatty acid synthase, proliferator-activated receptors alpha, and proliferator-activated receptors gamma. In QCD a metabolic rewiring occurs, as suggested by glycerol-3-phosphate dehydrogenase (GPD2), pyruvate dehydrogenase E1 component subunit beta, NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, and 4-trimethylaminobutyraldehyde dehydrogenase increment, while dihydrolipoyl dehydrogenase decreased. Macroautophagy is activated in QUC and IUC, with increased levels of p62, HSC70, major vault protein, myosin heavy chain 9, whereas it is blunted in QCD and ICD. The differing pattern of extracellular matrix, cytoskeletal derangements, cellular metabolism, and autophagy in UC and CD may contribute to the pathophysiological understanding of these disorders and serve as diagnostic markers in IBD patients.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Contribution of Extracellular Matrix and Signal Mechanotransduction to Epithelial Cell Damage in Inflammatory Bowel Disease Patients: A Proteomic Study

et al. 2017

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“…Other antibodies that are also known to associate with RA are anti-K8, anti-p68 and anti-Sa antibodies [ 70 ]. Keratin is a functionally diverse intermediate filament which is widely distributed in the human body [ 70 ]. K8 is one of the keratin types [ 70 ].…”

Section: Role Of Immune-related Secretory Molecules In Rheumatoid mentioning

confidence: 99%

“…Keratin is a functionally diverse intermediate filament which is widely distributed in the human body [ 70 ]. K8 is one of the keratin types [ 70 ]. The antibody reactive against K8 (anti-K8 antibody) has been demonstrated in about 68% of Han Chinese-originated RA patients [ 66 ].…”

Section: Role Of Immune-related Secretory Molecules In Rheumatoid mentioning

confidence: 99%

Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development

Yap

Tee

Wong

et al. 2018

Cells

327

242

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Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, inflammatory disorder that affects synovial joints, both small and large joints, in a symmetric pattern. This disorder usually does not directly cause death but significantly reduces the quality of life and life expectancy of patients if left untreated. There is no cure for RA but, patients are usually on long-term disease modifying anti-rheumatic drugs (DMARDs) to suppress the joint inflammation, to minimize joint damage, to preserve joint function, and to keep the disease in remission. RA is strongly associated with various immune cells and each of the cell type contributes differently to the disease pathogenesis. Several types of immunomodulatory molecules mainly cytokines secreted from immune cells mediate pathogenesis of RA, hence complicating the disease treatment and management. There are various treatments for RA depending on the severity of the disease and more importantly, the patient’s response towards the given drugs. Early diagnosis of RA and treatment with (DMARDs) are known to significantly improve the treatment outcome of patients. Sensitive biomarkers are crucial in early detection of disease as well as to monitor the disease activity and progress. This review aims to discuss the pathogenic role of various immune cells and immunological molecules in RA. This review also highlights the importance of understanding the immune cells in treating RA and in exploring novel biomarkers.

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“…In-gel digestion and mass spectrometry were performed as described previously [19]. The excised gel pieces were destained with 50% acetonitrile plus 25 mM NH 4 HCO 3 and dried by vacuum centrifugation, followed by addition of 25 mM NH 4 HCO 3 in 10 mM dithiothreitol to reduce it for 1 h at 57°C.…”

Section: In-gel Digestion and Mass Spectrometry Analysismentioning

confidence: 99%

Moesin expression is correlated with its involvement in patients with Behcet’s disease

Hussain

Chen

Zhang

et al. 2020

aoms

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Introduction: Behcet's disease (BD) is a rare, chronic autoimmune disorder of unknown etiology. Although the profile of autoantibodies for this disease is not yet completely understood, because of better disease recognition, its prevalence is increasing throughout the world. Among ERM proteins (ezrin/radixin/moesin), moesin is a member of a family which is involved in autoimmune diseases. The aim of this study is to confirm whether moesin is a potential anti-endothelial cell autoantigen (AECA) in Hans Chinese BD patients. Material and methods: First, a full length recombinant human moesin protein was over-expressed and purified. Second, it was identified by mass spectrometry and then purified moesin was used to perform Western blotting, immunoprecipitation and ELISA with confirmed BD patients. Finally, in vitro cytotoxicity experiments were conducted with anti-moesin antibodies by the resazurin reduction assay method. Results: Purified moesin protein was successfully expressed and then its antigenicity was confirmed by Western blotting and immunoprecipitation techniques. Anti-moesin antibodies were detected in approximately onethird (38%) of BD patients by ELISA and the reactivity of BD serum IgG antibodies against moesin was found to be significantly higher than HC (p < 0.0001). Moreover, in order to validate our results, cytotoxicity experiments also confirmed that anti-moesin antibody had a significant inhibitory effect on endothelial cell activity. Conclusions: Expression is correlated with the involvement of moesin as an autoantigen in BD pathology, which is a new finding. It might be a new candidate biomarker in the Han Chinese population.

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Keratin 8 is a novel autoantigen of rheumatoid arthritis

Cited by 11 publications

References 29 publications

Contribution of Extracellular Matrix and Signal Mechanotransduction to Epithelial Cell Damage in Inflammatory Bowel Disease Patients: A Proteomic Study

Contribution of Extracellular Matrix and Signal Mechanotransduction to Epithelial Cell Damage in Inflammatory Bowel Disease Patients: A Proteomic Study

Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development

Moesin expression is correlated with its involvement in patients with Behcet’s disease

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