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Relation between Escherichia coli R(rough)-forms in gut, lipid A in liver, and primary biliary cirrhosis
U Hopf1, B Möller, R Stemerowicz
1Medizinische Klinik und Poliklinik, Universitätsklinikum, Rudolf Virchow, Standort Charlottenburg, Berlin, West Germany.
Abstract:
Since antimitochondrial antibodies (AMA) specific to primary biliary cirrhosis (PBC) recognise enterobacterial proteins and can be induced by R(rough)-mutants of enterobacteriaceae a study was done to find out the prevalence of enterobacterial R-forms in stool samples of patients with chronic inflammatory liver diseases. Liver biopsy specimens were also examined for lipid A, a common antigenic component of the cell wall in gram-negative bacteria. In all stool samples from the 21 patients with PBC Escherichia coli R-forms constituted up to half of the total amount of E coli. In contrast E coli R-forms were detectable in the stools of only 1 healthy control (n = 20), and in 25% of patients with other cholestatic diseases (n = 10), chronic hepatitis type B (n = 15), type non-A, non-B hepatitis (n = 15), or chronic pancreatitis and fat malabsorption (n = 8). An immunoblot technique showed that E coli R-forms isolated from patients' stools contained PBC-specific AMA-reactive proteins with molecular weights of 70-80 kD and 50 kD. Deposits of lipid A, located primarily in the cytoplasm of hepatocytes, were found in 11 patients with PBC but not in the liver of patients with chronic viral hepatitis. Circulating antibodies against lipid A were found rarely and in low titres. The data support the hypothesis that intestinal enterobacterial R-forms are aetiologically important in PBC and that antigens released from the bacterial cell wall contribute to the pathogenesis of the disease.
Insights
Enterobacterial R-forms are prevalent in patients with primary biliary cirrhosis (PBC), suggesting a role in the disease. These gut bacteria may trigger the autoimmune response characteristic of PBC.
Area of Science:
- Immunology
- Gastroenterology
- Microbiology
Background:
- Antimitochondrial antibodies (AMA) in primary biliary cirrhosis (PBC) target enterobacterial proteins.
- Enterobacterial R-forms can induce AMA, prompting investigation into their role in liver disease.
Purpose of the Study:
- To determine the prevalence of enterobacterial R-forms in patients with chronic inflammatory liver diseases.
- To investigate the presence of lipid A in liver biopsies and circulating antibodies against it.
Main Methods:
- Stool samples analyzed for Escherichia coli R-forms.
- Liver biopsy examination for lipid A deposits.
- Immunoblotting to detect AMA-reactive proteins in isolated R-forms.
Main Results:
- Escherichia coli R-forms comprised up to 50% of E. coli in PBC patients' stools.
- R-forms were detected in only 1 healthy control and less frequently in other liver disease groups.
- PBC-specific AMA-reactive proteins (70-80 kD, 50 kD) were found in isolated E. coli R-forms.
- Lipid A deposits were present in PBC liver biopsies but not in viral hepatitis.
- Circulating anti-lipid A antibodies were rare and at low titers.
Conclusions:
- Intestinal enterobacterial R-forms are significantly associated with primary biliary cirrhosis.
- Bacterial cell wall antigens, like lipid A, likely contribute to PBC pathogenesis.
- Enterobacterial R-forms are a potential etiological factor in primary biliary cirrhosis.