Brief Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Hepatol. Oct 27, 2013; 5(10): 568-576
Published online Oct 27, 2013. doi: 10.4254/wjh.v5.i10.568
Presence of disease specific autoantibodies against liver sinusoidal cells in primary biliary cirrhosis
Ourania Sfakianaki, Maria Tzardi, Argyro Voumvouraki, Aikaterini Afgoustaki, Meri Koulentaki, Elias Kouroumalis
Ourania Sfakianaki, Argyro Voumvouraki, Elias Kouroumalis, Liver Research Laboratory, Medical School, University of Crete, 71003 Voutes, Crete, Greece
Maria Tzardi, Department of Pathology, University Hospital of Heraklion, 71100 Voutes, Crete, Greece
Aikaterini Afgoustaki, Meri Koulentaki, Elias Kouroumalis, Department of Gastroenterology, University Hospital of Heraklion, 71100 Voutes, Crete, Greece
Author contributions: Sfakianaki O and Voumvouraki A performed the research; Koulentaki M collected the data; Tzardi M interpreted the pathological data; Sfakianaki O and Kouroumalis E interpreted the results; Sfakianaki O and Afgoustaki A wrote the manuscript; Sfakianaki O and Kouroumalis E planned and coordinated the study; Tzardi M, Voumvouraki A, Koulentaki M and Kouroumalis E revised the manuscript; all authors read and approved the manuscript.
Correspondence to: Elias Kouroumalis, MD, PhD, Professor, Department of Gastroenterology, University Hospital of Heraklion, P.O.BOX 1352, 71100 Heraklion, Crete, Greece. kouroum@ med.uoc.gr
Telephone: +30-2810-392356 Fax: +30-2810-542085
Received: May 12, 2013
Revised: August 10, 2013
Accepted: September 13, 2013
Published online: October 27, 2013
Processing time: 165 Days and 9.5 Hours
Abstract

AIM: To investigate the presence of autoantibodies directed against liver sinusoidal cells in primary biliary cirrhosis (PBC).

METHODS: Liver biopsies from 21 PBC patients were studied and compared with 12 liver biopsies from disease controls [3 patients with hepatitis B (HBV) virus, 3 patients with hepatitis C virus (HCV), 3 patients with non-alcoholic steatohepatitis and 3 patients with acute alcoholic hepatitis (AAH)]. As healthy controls, we used tissue specimens adjacent to metastatic liver adenocarcinoma. Normal serum was taken from staff members of the unit. The determination of the cell type targeted by autoantibodies present in the patients sera was performed by indirect immunofluorescence (IIF) analysis using paraffin-embedded liver sections as a substrate. Sera from homologous or heterologous PBC patients or sera from the disease control group were used as primary antibodies. The presence of autoantibodies was identified using confocal microscopy.

RESULTS: In total, 18/21 (85.7%) PBC patients exhibited positive staining in the sinusoidal cells, 10/21 (47.6%) in lymphocytes, 8/21 (38%) in cholangiocytes and 7/21 (33.3%) in hepatocytes, when homologous serum and fluorescein isothiocyanate-conjugated immunoglobulin type G (IgG) secondary antibody were used. PBC sections incubated with heterologous PBC serum showed reduced staining (20% for sinusoidal cells, 20% for lymphocytes, 20% for cholangiocytes and 13.3% for hepatocytes). When IgM immunoglobulin, instead of IgG, was used as secondary antibody, positive staining was observed in 75% of lymphocytes, 62.5% of cholangiocytes, 37.5% of hepatocytes and 50% of the sinusoidal cells with a much stronger staining intensity. No staining was observed when either normal or PBC sera were used as a primary antibody on liver sections from the disease control group. When PBC sera were incubated with healthy control sections, weak positive staining of cholangiocytes was observed in 3/21 (14.3%) PBC serum samples. Steatohepatitis serum on PBC sections gave a positive staining of some hepatocytes and lymphocytes but no staining on viral hepatitis sections. Incubation with HBV sera stained some hepatocytes, cholangiocytes and intra-sinusoidal or portal lymphocytes of PBC, HBV and AAH patients but not HCV patients.

CONCLUSION: In this study, for the first time in diseased liver tissue, we have demonstrated that a large proportion of PBC patients have disease specific autoantibodies against liver sinusoidal cells.

Keywords: Primary biliary cirrhosis; Autoantibodies; Sinusoidal cells; Cholangiocytes; Liver tissue

Core tip: In this study, indirect immunofluorescence staining was performed on paraffin-embedded human liver sections of various chronic liver diseases to demonstrate the presence of disease specific autoantibodies targeting sinusoidal cells in patient sera. Liver sections from normal and disease controls were used as the substrate, and sera were the source of primary antibodies. Our findings indicate that disease specific antibodies against liver sinusoidal cells circulate in primary biliary cirrhosis (PBC). Various non disease specific antibodies were also found in PBC and chronic hepatitis B but not in other chronic liver diseases.