Immune Dysfunction and Albumin-Related Immunity in Liver Cirrhosis

Liver cirrhosis yearly causes 1.2 million deaths worldwide, ranking as the 10th leading cause of death in the most developed countries. High susceptibility to infections along with a significant risk for infection-related mortality justifies the description of liver cirrhosis as the world’s most com...

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Main Authors: Benjamin Wilde, Antonios Katsounas
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2019/7537649
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author Benjamin Wilde
Antonios Katsounas
author_facet Benjamin Wilde
Antonios Katsounas
author_sort Benjamin Wilde
collection DOAJ
description Liver cirrhosis yearly causes 1.2 million deaths worldwide, ranking as the 10th leading cause of death in the most developed countries. High susceptibility to infections along with a significant risk for infection-related mortality justifies the description of liver cirrhosis as the world’s most common immunodeficiency syndrome. Liver cirrhosis is an end-stage organic disease hallmarked by a multifaceted immune dysfunction due to deterioration of antimicrobial recognition and elimination mechanisms in macrophages along with an impaired antigen presentation ability in circulating monocytes. Bacterial translocation supports—and is supported by—uncontrolled activation of immune cell responses and/or loss of toll-like receptor (TLR) tolerance, which can turn exaggerated inflammatory responses to systemic inflammation. Lipopolysaccharide (LPS) or endotoxin boosts systemic inflammatory activity through activation of TLR-2- and TLR-4-dependent pathways and facilitate a massive production of cytokines. This, in turn, results into elevated secretion of reactive oxygen species (ROS), which further enhances intestinal hyperpermeability and thus sustains a vicious circle of events widely known as “leaky gut.” Albumin can be of particular benefit in cirrhotic patients with spontaneous bacterial peritonitis and/or hepatorenal syndrome type of acute kidney injury (HRS-AKI) due to anti-inflammatory and antioxidative stress as well as volume-expanding properties and endothelial-stabilizing attributes. However, presence of autoantibodies against albumin in patients with liver cirrhosis has been described. Although previous research suggested that these antibodies should be regarded as naturally occurring antibodies (NOA), the origin of the antialbumin immune response is obscure. High occurrence of NAO/albumin complexes in patients with liver disease might reflect a limited clearance capacity due to bypassing portal circulation. Moreover, high burden of oxidized albumin is associated with less favorable outcome in patients with liver cirrhosis. To date, there is no data available as to whether oxidized forms of albumin result in neoepitopes recognized by the immune system. Nevertheless, it is reasonable to hypothesize that these alterations may have the potential to induce antialbumin immune responses and thus favor systemic inflammation.
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spelling doaj-art-e0550f168e084cfba27d890941e388402025-08-20T02:21:28ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/75376497537649Immune Dysfunction and Albumin-Related Immunity in Liver CirrhosisBenjamin Wilde0Antonios Katsounas1Department of Nephrology, University Hospital Essen, University Duisburg Essen, Hufelandstrasse 55, 45122 Essen, GermanyDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Magdeburg, Leipzigerstrasse 44, 39120 Magdeburg, GermanyLiver cirrhosis yearly causes 1.2 million deaths worldwide, ranking as the 10th leading cause of death in the most developed countries. High susceptibility to infections along with a significant risk for infection-related mortality justifies the description of liver cirrhosis as the world’s most common immunodeficiency syndrome. Liver cirrhosis is an end-stage organic disease hallmarked by a multifaceted immune dysfunction due to deterioration of antimicrobial recognition and elimination mechanisms in macrophages along with an impaired antigen presentation ability in circulating monocytes. Bacterial translocation supports—and is supported by—uncontrolled activation of immune cell responses and/or loss of toll-like receptor (TLR) tolerance, which can turn exaggerated inflammatory responses to systemic inflammation. Lipopolysaccharide (LPS) or endotoxin boosts systemic inflammatory activity through activation of TLR-2- and TLR-4-dependent pathways and facilitate a massive production of cytokines. This, in turn, results into elevated secretion of reactive oxygen species (ROS), which further enhances intestinal hyperpermeability and thus sustains a vicious circle of events widely known as “leaky gut.” Albumin can be of particular benefit in cirrhotic patients with spontaneous bacterial peritonitis and/or hepatorenal syndrome type of acute kidney injury (HRS-AKI) due to anti-inflammatory and antioxidative stress as well as volume-expanding properties and endothelial-stabilizing attributes. However, presence of autoantibodies against albumin in patients with liver cirrhosis has been described. Although previous research suggested that these antibodies should be regarded as naturally occurring antibodies (NOA), the origin of the antialbumin immune response is obscure. High occurrence of NAO/albumin complexes in patients with liver disease might reflect a limited clearance capacity due to bypassing portal circulation. Moreover, high burden of oxidized albumin is associated with less favorable outcome in patients with liver cirrhosis. To date, there is no data available as to whether oxidized forms of albumin result in neoepitopes recognized by the immune system. Nevertheless, it is reasonable to hypothesize that these alterations may have the potential to induce antialbumin immune responses and thus favor systemic inflammation.http://dx.doi.org/10.1155/2019/7537649
spellingShingle Benjamin Wilde
Antonios Katsounas
Immune Dysfunction and Albumin-Related Immunity in Liver Cirrhosis
Mediators of Inflammation
title Immune Dysfunction and Albumin-Related Immunity in Liver Cirrhosis
title_full Immune Dysfunction and Albumin-Related Immunity in Liver Cirrhosis
title_fullStr Immune Dysfunction and Albumin-Related Immunity in Liver Cirrhosis
title_full_unstemmed Immune Dysfunction and Albumin-Related Immunity in Liver Cirrhosis
title_short Immune Dysfunction and Albumin-Related Immunity in Liver Cirrhosis
title_sort immune dysfunction and albumin related immunity in liver cirrhosis
url http://dx.doi.org/10.1155/2019/7537649
work_keys_str_mv AT benjaminwilde immunedysfunctionandalbuminrelatedimmunityinlivercirrhosis
AT antonioskatsounas immunedysfunctionandalbuminrelatedimmunityinlivercirrhosis