Relation between Escherichia coli R(rough)-forms in gut, lipid A in liver, and primary biliary cirrhosis.
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.
Hopf
U
U
Medizinische Klinik und Poliklinik, Universitätsklinikum, Rudolf Virchow, Standort Charlottenburg, Berlin, West Germany.
Möller
B
B
Stemerowicz
R
R
Lobeck
H
H
Rodloff
A
A
Freudenberg
M
M
Galanos
C
C
Huhn
D
D
D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000032:analysis*; D002473:Cell Wall / Q000382:microbiology; D002908:Chronic Disease; D004926:Escherichia coli / Q000145:classification* / Q000276:immunology / Q000302:isolation & purification; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D008050:Lipid A / Q000032:analysis* / Q000276:immunology; D008099:Liver / Q000032:analysis*; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology; D008970:Molecular Weight
D001323:Autoantibodies; D008050:Lipid A