Serum Anti-Fumarate Hydratase Autoantibody as a Biomarker for Predicting Prognosis of Acute-on-Chronic Liver Failure
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). Methods: An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. Results: Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach. Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. Conclusions: The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF.
Abstract
Background/Aims: To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). Methods: An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. Results: Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach. Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. Conclusions: The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF.
참고문헌 (29)
- Arroyo V, "Acute-on-chronic liver failure", N Engl J Med, 382, pp.2137~2145 (2020)
- Ramzan M, "Comparison of CLIF-C ACLF score and MELD score in predicting ICU mortality in patients with acute-on-chronic liver failure", Cureus, 12, pp.e7087~ (2020)
- Sundaram V, "Factors associated with survival of patients with severe acute-on-chronic liver failure before and after liver transplantation", Gastroenterology, 156, pp.1381~1391 (2019)
- Xie Z, "A prognostic model for hepatitis B acute-on-chronic liver failure patients treated using a plasma exchange-centered liver support system", J Clin Apher, 35, pp.94~103 (2020)
- Peng B, "Using immunoproteomics to identify alpha-enolase as an autoantigen in liver fibrosis", J Proteome Res, 12, pp.1789~1796 (2013)
- Xiao ZX, "An updated advance of autoantibodies in autoimmune diseases", Autoimmun Rev, 20, pp.102743~ (2021)
- Fulton KM, "Immunoproteomics methods and techniques", Methods Mol Biol, 2024, pp.25~58 (2019)
- Wang T, "Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma", World J Gastroenterol, 23, pp.3496~3504 (2017)
- Nie H, "Correlative analysis of different HBV genotypes and autoantibodies in hepatitis B patients", Zhonghua Gan Zang Bing Za Zhi, 20, pp.448~452 (2012)
- Marconcini ML, "Autoantibody profile in individuals with chronic hepatitis C", Rev Soc Bras Med Trop, 46, pp.147~153 (2013)
- Wang T, "Serum anti-14-3-3 zeta autoantibody as a biomarker for predicting hepatocarcinogenesis", Front Oncol, 11, pp.733680~ (2021)
- Narkewicz MR, "Prevalence and significance of autoantibodies in children with acute liver failure", J Pediatr Gastroenterol Nutr, 64, pp.210~217 (2017)
- Jain V, "Autoimmune acute liver failure and seronegative autoimmune liver disease in children : are they different from classical disease?", Eur J Gastroenterol Hepatol, 29, pp.1408~1415 (2017)
- Sarin SK, "Acute-onchronic liver failure : consensus recommendations of the Asian Pacific association for the study of the liver(APASL) : an update", Hepatol Int, 13, pp.353~390 (2019)
- Li Q, "Acute-on-chronic liver failure from chronic-hepatitis-B, who is the behind scenes", Front Microbiol, 11, pp.583423~ (2020)
- Tang X, "Tri-typing of hepatitis B-related acute-on-chronic liver failure defined by the World Gastroenterology Organization", J Gastroenterol Hepatol, 36, pp.208~216 (2021)
- Sun Z, "Circulating proteomic panels for diagnosis and risk stratification of acute-on-chronic liver failure in patients with viral hepatitis B", Theranostics, 9, pp.1200~1214 (2019)
- Sun MY, "Analysis of prognosis-related factors in patients with hepatitis B virus-related acute-on-chronic liver failure", Zhonghua Gan Zang Bing Za Zhi, 29, pp.983~986 (2021)
- Kabbani AR, "Treatment strategies for acute-on-chronic liver failure", Med Klin Intensivmed Notfmed, 116, pp.3~16 (2021)
- Wu HH, "Heat shock protein 70(HSP70)reduces hepatic inflammatory and oxidative damage in a rat model of liver ischemia", reperfusion injury with hyperbaric oxygen preconditioning, 2018, pp.24, 8096~8104
- Oweira H, "Serum caspase-cleaved cytokeratin(M30)indicates severity of liver dysfunction and predicts liver outcome", Ann Transplant, 23, pp.393~400 (2018)
- Dik E, "Human fumarate hydratase is dual localized by an alternative transcription initiation mechanism", Traffic, 17, pp.720~732 (2016)
- Wentzel JF, "Exposure to high levels of fumarate and succinate leads to apoptotic cytotoxicity and altered global DNA methylation profiles in vitro", Biochimie, 135, pp.28~34 (2017)
- Kerins MJ, "Fumarate mediates a chronic proliferative signal in fumarate hydratase-inactivated cancer cells by increasing transcription and translation of ferritin genes", Mol Cell Biol, 37, pp.e00079~17 (2017)
- Noguchi S, "Direct and quantitative analysis of altered metabolic flux distributions and cellular ATP production pathway in fumarate hydratase-diminished cells", Sci Rep, 10, pp.13065~ (2020)
- Zhao Y, "Fumarate hydratase-specific T cell response in Chinese patients with autoimmune hepatitis", Clin Res Hepatol Gastroenterol, 42, pp.339~346 (2018)
- Sun G, "Integrated molecular characterization of fumarate hydratase-deficient renal cell carcinoma", Clin Cancer Res, 27, pp.1734~1743 (2021)
- Burgener AV, "SDHA gain-offunction engages inflammatory mitochondrial retrograde signaling via KEAP1-Nrf2", Nat Immunol, 20, pp.1311~1321 (2019)
- Fan Z, "Anti-senescence role of heterozygous fumarate hydratase gene knockout in rat lung fibroblasts in vitro", Aging(Albany NY), 11, pp.573~589 (2019)
