Lipoteichoic acid may affect the pathogenesis of bile duct damage in primary biliary cirrhosis

Aim: Intrahepatic bile ducts are the targets for inflammation in primary biliary cirrhosis (PBC), but their pathogenesis is not known. Gram-positive bacterial DNA was detected recently in gallbladder bile of PBC patients. In the present study, we assessed the possible pathological role of lipoteichoic acid (LTA), the Gram-positive bacterial cell wall component, in PBC.

Methods: Liver samples, obtained from 20 patients with PBC (stage 1–2 with CNSDC: stage 3–4 with loss of bile ducts = 10:10) and from 13 patients with chronic hepatitis due to hepatitis C virus (CH–C) with lymphocytic cholangitis, were subjected to immunohistochemical staining with polyclonal rabbit anti-LTA as the primary antibody. Serum reactivities to LTA were studied by ELISA. After 1 μg of purified LTA was placed in a 96-well microplate as an antigen, an antibody capture assay was carried out using serum samples from PBC (n = 20), CH–C (n = 13) and healthy subjects (n = 11).

Results: LTA was localized around the sites of chronic non-suppurative destructive cholangitis (CNSDC) in the portal area in stage 1–2 PBC but was not detected in the portal area in CH–C. In stage 3–4 PBC, LTA was localized around sites of ductular proliferation at the periphery of portal tracts. IgM class anti-LTA serum titers were significantly higher in PBC than in CH–C. IgA class anti-LTA serum titers were significantly higher in PBC than in healthy subjects.

Conclusions: In the PBC livers, the profile of immunoreactivity to LTA changed markedly as the disease progressed. Sera from PBC showed higher levels of anti-LTA titers than CH–C (IgM) or from healthy subjects (IgA). The LTA-mediated immune system might affect the initiation and/or progression of PBC.