Serum cytochrome c and m30‐neoepitope of cytokeratin‐18 in chronic hepatitis C

Parfieniuk‐Kowerda, Anna; Łapiński, Tadeusz Wojciech; Rogalska, Magdalena; Świderska, Magdalena; Panasiuk, Andrzej; Jaroszewicz, Jerzy; Flisiak, Robert

doi:10.1111/liv.12297

Cited by 32 publications

(20 citation statements)

References 39 publications

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“…Similarly, patients with chronic HBV infection showed higher serum M30 levels compared to healthy controls . M30 serum levels correlated with histological disease activity in chronic HCV or HBV infection . Vice versa , M30 levels declined with successful antiviral treatment of chronic HCV or HBV infection .…”

Section: Role Of K18 Biomarkers In Chronic Liver Diseasesmentioning

confidence: 83%

Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver

et al. 2016

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Keratins, formerly known as cytokeratins, are the major epithelial-specific subgroup of intermediate filament proteins. Adult hepatocytes express keratin polypeptides 8 and 18 (K8/K18), while cholangiocytes express K8/K18 and keratins 7 and 19 (K7/K19). Keratins function primarily to protect hepatocytes from apoptosis and necrosis, which was revealed using several genetic mouse models. This cytoprotective function was further clarified by the identification of natural human keratin variants that are normally silent but become pathogenic by predisposing their carriers to apoptosis during acute or chronic liver injury mediated by toxins, virus infection or metabolic stress. During apoptosis, caspases cleave K18 and K19 at conserved aspartates (for human K18/K19: 235Val-Glu-Val-Asp↓) and K18 at a unique aspartate (for human K18: 394Asp-Ala-Leu-Asp↓), with the latter exposed epitope becoming recognized by the M30 antibody in blood and tissues. Additional K18-containing protein backbone epitopes are detected using the M6 and M5 (termed M65) antibodies. Intact K18 and its associated fragments, which are released into blood during apoptosis and necrosis in various diseases, have been analyzed by ELISA using the M30/M65 antibodies or their signal ratios. Furthermore, M30/M65 levels have been used as diagnostic and prognostic biomarkers in acute and chronic liver diseases including nonalcoholic steatohepatitis and acute liver failure. Other keratin biomarkers include K18-related tissue polypeptide antigen, K8-related tissue-specific antigen, and K19-related CYFRA-21-1, which have been evaluated mostly in patients with epithelial tumors. Conclusion Keratins and their fragments are released into blood during liver injury. The epithelial specificity of K18/K19, epitope unmasking upon caspase digestion, abundance and relative stability render them useful biomarkers for hepatocyte and cholangiocyte apoptosis and necrosis. However, the precise biochemical nature and release mechanism of circulating keratins remain unknown.

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Section: Role Of K18 Biomarkers In Chronic Liver Diseasesmentioning

confidence: 83%

Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver

et al. 2016

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“…The presence of HIV virus in Kupffer cells consequently leads to productive infection (Crane et al, 2012). Cell apoptosis, a highly regulated process, occurs during many physiological as well as pathological processes (Parfieniuk-Kowerda et al, 2013) and can be triggered by the extrinsic (death receptor) or the intrinsic (mitochondrial) death pathways. In HIV infection exaggerated cell apoptosis has been reported by many authors (Hansjee et al, 2004;Vassena et al, 2007;Mhawej et al, 2009), some of them suggesting that higher levels of apoptosis are associated with worse outcomes due to slower recovery of CD4+ T lymphocyte number (de Oliveira Pinto et al, 2002;Roger et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…During apoptosis several regulatory substances are released into the bloodstream, including cell mitochondrial protein cytochrome-c (Cyt-c) (Parfieniuk-Kowerda et al, 2013) and Cytokeratin 18 neoepitope. Cytokeratin 18 (CK18) filaments are major components of the cytoskeleton of hepatocytes, but also occur in epithelial and parenchymal cells in smaller amounts.…”

Section: Introductionmentioning

confidence: 99%

Difference in Markers of Microbial Translocation and Cell Apoptosis in HIV Monoinfected and HIV/HCV Coinfected Patients

Madelāne

Krūmiņa

Sīmanis

et al. 2019

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

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Immune activation in human immunodeficiency virus (HIV) infection is driven by microbial translocation and in HIV patients is one of the contributors to faster progression of liver disease along with increased cell apoptosis. The aim of the study was to compare microbial translocation and apoptosis markers in HIV monoinfected and HIV/hepatitis C virus (HCV) coinfected patients, depending on HIV immune status and antiretroviral treatment (ART). We analysed data for 78 HIV monoinfected and 105 HIV/HCV coinfected patients from the Rīga East University Hospital. Lipopolysaccharide (LPS), endotoxin core antibodies (EndoCAb), cytokeratin 18 (CK18) and cyto-chrome c (Cyt-c) levels were measured. No significant difference in LPS, EndoCAb, Cyt-c levels between HIV and HIV/HCV patients was found. The CK18 level was higher in the HIV/HCV group. Correlation between CD4+ cell count and EndoCAb antibodies was found in HCV positive patients. There was a significant effect of ART on markers for EndoCAb IgA and EndoCAb IgM antibodies in the HIV monoinfected group. Correlation between CD4+ cell count and EndoCAb antibodies and LPS was found in HIV/HCV patients on ART. Coinfection with HCV can lead to more pronounced response in EndoCAb antibody production and higher levels of cell apoptosis markers, despite similar LPS levels. ART has a positive effect on immune activation.

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“…In acute and chronic HCV reinfection, ALT levels were significantly and positively correlated with M30S, a fact which has been described earlier in chronic HCV infection . However, ALT levels were not able to discriminate either acute from chronic HCV reinfection ( P = 0.121) or acute HCV reinfection from acute rejection ( P = 0.941) in contrast to (cleaved) CK18 measurements.…”

Section: Discussionmentioning

confidence: 55%

(Cleaved) CK18 serum and tissue expression levels differentiate acute HCV reinfection from acute rejection in liver allografts

Reis

Wohlschläger

Hagemann

et al. 2014

Liver International

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M30-, M65-ELISAs and M30-immunohistochemistry are potential useful tools in differentiating acute HCV reinfection from acute rejection facilitating both speed and accuracy of the diagnostic process for the clinician and hepatopathologist. In this context, M65S provided superior diagnostic characteristics compared to M30-based methods. However, being the first analysis of (cleaved) CK18 serum and tissue expression levels in this context, the results need to be verified in further studies.

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Serum cytochrome c and m30‐neoepitope of cytokeratin‐18 in chronic hepatitis C

Cited by 32 publications

References 39 publications

Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver

Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver

Difference in Markers of Microbial Translocation and Cell Apoptosis in HIV Monoinfected and HIV/HCV Coinfected Patients

(Cleaved) CK18 serum and tissue expression levels differentiate acute HCV reinfection from acute rejection in liver allografts

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