Maaike Biewenga1, Arantza Farina Sarasqueta2, Maarten E Tushuizen3, Eveline S M de Jonge-Muller3, Bart van Hoek3, Leendert A Trouw4. 1. Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: M.Biewenga@lumc.nl. 2. Department of Pathology, Amsterdam University Medical Center, Amsterdam, the Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands. 3. Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands. 4. Department of Immunohematology and Blood transfusion, Leiden University Medical Center, Leiden, the Netherlands.
Abstract
INTRODUCTION: The complement system, an essential part of the innate immune system, is involved in various autoimmune diseases. Activation of the complement system by autoantibodies results in immune activation and tissue damage. At the moment little is known about the role of the complement system in autoimmune liver disease, including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Since inhibition of the complement system is currently being tested in several autoimmune diseases as a therapeutic option, its role in autoimmune liver disease requires further clarification. METHODS: A review of the literature was performed on studies investigating complement activation in PBC, PSC and AIH. Since data on AIH were lacking immunohistochemical staining for IgG, C1q, C3d, C4d and C5b9 was performed on liver tissue of nine AIH patients, two healthy controls and one positive control (acute liver failure caused by paracetamol intoxication). RESULTS: Immunohistochemical analysis in AIH revealed increased production of C3 and C4 by hepatocytes. Despite a strong staining for IgG in the immune infiltrate in AIH, C3d, C4d and C5b9 deposition was only present in one AIH patient and the deposition was restricted to the interface between portal tracts and liver parenchyma. No deposition was found in all other AIH patients or healthy controls. Literature review showed raised plasma C3 and C4 levels in AIH, PBC and PSC patients compared to healthy controls. For PBC and PSC no complement depositions at the bile ducts were reported. CONCLUSION AND DISCUSSION: Although complement is involved in various autoimmune diseases, the role of complement in autoimmune liver disease seems limited. Therefore it is unlikely that complement inhibition will become a novel treatment option for these diseases.
INTRODUCTION: The complement system, an essential part of the innate immune system, is involved in various autoimmune diseases. Activation of the complement system by autoantibodies results in immune activation and tissue damage. At the moment little is known about the role of the complement system in autoimmune liver disease, including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Since inhibition of the complement system is currently being tested in several autoimmune diseases as a therapeutic option, its role in autoimmune liver disease requires further clarification. METHODS: A review of the literature was performed on studies investigating complement activation in PBC, PSC and AIH. Since data on AIH were lacking immunohistochemical staining for IgG, C1q, C3d, C4d and C5b9 was performed on liver tissue of nine AIHpatients, two healthy controls and one positive control (acute liver failure caused by paracetamol intoxication). RESULTS: Immunohistochemical analysis in AIH revealed increased production of C3 and C4 by hepatocytes. Despite a strong staining for IgG in the immune infiltrate in AIH, C3d, C4d and C5b9 deposition was only present in one AIHpatient and the deposition was restricted to the interface between portal tracts and liver parenchyma. No deposition was found in all other AIHpatients or healthy controls. Literature review showed raised plasma C3 and C4 levels in AIH, PBC and PSC patients compared to healthy controls. For PBC and PSC no complement depositions at the bile ducts were reported. CONCLUSION AND DISCUSSION: Although complement is involved in various autoimmune diseases, the role of complement in autoimmune liver disease seems limited. Therefore it is unlikely that complement inhibition will become a novel treatment option for these diseases.
Authors: Maaike Biewenga; Sebastiaan Heidt; Manon Vergunst; Camiel M J Marijnissen; Rob A de Man; Annemiek A van der Eijk; Adriaan J van der Meer; Leendert A Trouw; Bart van Hoek Journal: JHEP Rep Date: 2022-02-22