Elevation of Autoantibodies to Cerebral Proteins in Hepatic Encephalopathy: Another Pathogenic Factor?

Manzhalii, Elina; Falalyeyeva, Tetyana; Moyseyenko, Valentyna; Weiskirchen, Ralf; Stremmel, Wolfgang

doi:10.1159/000516412

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…Ammonia being a neurotoxin affects brian function. Pro-inflammation, autoimmunity to brain antigens (7) and abnormalities in neuro-transmission mechanisms are also associated with HE pathogenesis (8,9) . Lowering the neurotoxin levels in serum improves HE conditions.…”

Section: Introductionmentioning

confidence: 99%

Association Of Electroencephalogram Patterns With Ammonia Levels In Hepatic Encephalopathy Patients

Fatima,

Shah,

Khan

et al. 2023

JRMC

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Objective: To find out the association between electroencephalogram (EEG) and hepatic encephalopathy. Methodology: This cross-sectional study included 100 patients (with the age of52.5±6.09years for males and 51.7 ± 6.10 years for females) of reported hepatic encephalopathy, visiting the medical department (indoor and OPD) at Federal Government Polyclinic Hospital, Islamabad. The study was conducted from January 2020 to May 2021. Patients who had known epileptic and structural brain lesions or strokes were excluded from the study. Statistical analysis was done using GraphPad Prism software. The significance of data (p-value or R2 value) was calculated through a two-tailed test or correlation coefficient. Results: All the patients in hepatic encephalopathy grade IV reported abnormal EEG representing triphasic waves and flattening of EEG pattern. There was no correlation observed between age, gender and hepatic encephalopathy grades. However, a significant correlation (R2= 0.9032) was observed between serum ammonia levels and hepatic encephalopathy grades. Elevated serum ammonia levels depicted the severity of hepatic encephalopathy. Overall, the percentage of patients with abnormal EEG increased with increasing grade of hepatic encephalopathy. It was quite intriguing to note that EEG, being the common method to diagnose hepatic encephalopathy grades, is not dependent on patients’ socio-economic status. Conclusion: Data concluded that serum ammonia levels are well associated with the progression of hepatic encephalopathy. Moreover, the EEG patter provides the appropriate information about the neurological abnormalities associated with the severity of hepatic encephalopathy. Hence, serum ammonia levels and EEG both should accurately be used as indicators for diagnosis and monitoring the response to the treatment of various grades of hepatic encephalopathy. Data warrant further investigations to get a better insight into hepatic encephalopathy's relationship with EEG patterns through the inclusion of molecular parameters.

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Section: Introductionmentioning

confidence: 99%

Association Of Electroencephalogram Patterns With Ammonia Levels In Hepatic Encephalopathy Patients

Fatima,

Shah,

Khan

et al. 2023

JRMC

View full text Add to dashboard Cite

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“…The pathogenesis of HE is still not fully clarified. Multiple factors have been proposed to contributed to the pathophysiological process of HE, including excessive formation of ammonia, impaired brain energy metabolism ( Butterworth, 2014 ; Haussinger et al, 2021 ), inflammation ( Coltart et al, 2013 ), neuronal autoantibody elevation ( Manzhalii et al, 2021 ), autophagic flux in astrocytes ( Lu et al, 2019 ) and specific gut microbial taxa ( Ahluwalia et al, 2016 ). HE is associated with poor quality of life, increased morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Knockout Screen Identifies EGLN3 Involving in Ammonia Neurotoxicity

Chen

et al. 2022

Front. Cell Dev. Biol.

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Hepatic encephalopathy (HE) is a brain dysfunction associated with poor quality of life, increased morbidity and mortality. The pathogenesis of HE is still not fully clarified and effective therapeutic strategies are imperative. Among multiple factors that contribute to the pathophysiological process of HE, ammonia neurotoxicity is thought to be central in the pathogenesis of HE. Therefore, in this study, we subjected SH-SY5Y cells to ammonia insult and performed a pooled genome-wide CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) knockout screen to unveil the underlying molecular mechanisms of ammonia neurotoxicity and discover new potential therapeutic targets for HE. We found that EGLN3 (egl-9 family hypoxia-inducible factor 3) UCP3,GTPBP5, OR4D11 and SDR9C7 with 6 unique sgRNAs may contribute to protection against ammonia injury, while EGLN3 may be most related to ammonia resistance. We knocked down EGLN3 by transfecting neurons with specific shRNA lentivirus and confirmed that EGLN3 knockdown decreased ammonia-induced caspase-3 activation and apoptosis. We also demonstrated that EGLN3 knockdown ameliorated ammonia induced decreased expression of Bcl-2, increased expression of Bax and inhibited release of cytochrome c into the cytosol in neurons, suggesting that EGLN3 inhibition protected against ammonia induced apoptosis through mitochondrial dependent apoptosis pathway. Future therapeutic strategies regulating EGLN3 may be applied to the management of HE.

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Argonaute-2 autoantibodies: a promising biomarker for predicting mortality in HBV-related acute-on-chronic liver failure patients with cirrhosis

Wang,

Hu,

et al. 2024

Front. Cell. Infect. Microbiol.

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Background & aimsHBV infection initiates autoimmune responses, leading to autoantibody generation. This research explores the role of autoantibodies in HBV-related Acute-on-Chronic Liver Failure (ACLF), offering novel perspectives for clinical management.MethodWe applied immunoprecipitation and iTRAQ techniques to screen for autoantibodies in serum from HBV-related cirrhosis patients and conducted detection with conformation- stabilizing ELISA in a cohort of 238 HBV-infected individuals and 49 health controls. Our results were validated in a retrospective cohort comprising 106 ACLF patients and further assessed through immunohistochemical analysis in liver tissues from an additional 10 ACLF cases.ResultsUtilizing iTRAQ, we identified Argonaute1-3 autoantibodies (AGO-Abs) in this research. AGO2-Abs notably increased in cirrhosis, decompensation, and further in ACLF, unlike AGO1-Abs and AGO3-Abs. This reflects disease severity correlation. Logistic regression and COX models confirmed AGO2-Abs as independent prognostic indicators for decompensated liver cirrhosis (DLC) and ACLF. In the ROC analysis, AGO2-Abs showed significant diagnostic value for predicting 28- and 90-day mortality (AUROC = 0.853 and 0.854, respectively). Furthermore, combining AGO2-Abs with the Child-Pugh, MELD, and AARC scores significantly improved their predictive accuracy (P < 0.05). Kaplan-Meier analysis showed poorer survival for AGO2-Abs levels above 99.14μg/ml. These findings were supported by a retrospective validation cohort. Additionally, immunohistochemistry revealed band-like AGO2 expression in periportal liver areas, with AGO2-Abs levels correlating with total bilirubin, indicating a potential role in exacerbating liver damage through periportal functions.ConclusionsAGO2-Abs is a robust biomarker for predicting the mortality of patients with HBV-related ACLF.

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Elevation of Autoantibodies to Cerebral Proteins in Hepatic Encephalopathy: Another Pathogenic Factor?

Cited by 3 publications

References 21 publications

Association Of Electroencephalogram Patterns With Ammonia Levels In Hepatic Encephalopathy Patients

Association Of Electroencephalogram Patterns With Ammonia Levels In Hepatic Encephalopathy Patients

Genome-Wide Knockout Screen Identifies EGLN3 Involving in Ammonia Neurotoxicity

Argonaute-2 autoantibodies: a promising biomarker for predicting mortality in HBV-related acute-on-chronic liver failure patients with cirrhosis

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