Oral tolerance and pyruvate dehydrogenase in patients with primary biliary cirrhosis.
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the immunological destruction of intralobular bile ducts and serum anti-mitochondrial antibodies (AMA). Based upon previous work of oral tolerance and autoimmunity, we hypothesized that feeding the mitochondrial autoantigens of PBC would alter the clinical course and the level of antimitochondrial antibodies. The bovine pyruvate dehydrogenase complex (PDC) was purified and 5 mg fed in gelatin capsules to 6 patients with early stage PBC for 6 months. Antimitochondrial antibodies and liver biochemistries were measured at every 3 months for 12 months. The clinical trial was completed for all patients except for 1 who showed deterioration of pre-existing skin rash during treatment, which disappeared within 2 weeks after treatment was discontinued. However, after 1 year, neither the titers of AMAs nor liver biochemistries were significantly changed by this treatment. This is the first trial to test the efficacy of oral tolerance induction in PBC. However, the data, which limited in scope, did not demonstrate efficacy and further highlights the difficulties in showing continuing evidence of tolerance induction in autoimmunity.
Suzuki
Ayako
A
Division of Gastroenterology and Hepatology, Mayo Clinic, W19A, 200 First Street, SW, Rochester, MN 55905, USA.
Van de Water
Judy
J
Gershwin
M Eric
ME
Jorgensen
Roberta
R
Angulo
Paul
P
Lindor
Keith
K
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage; D015551:Autoimmunity; D002417:Cattle; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D008105:Liver Cirrhosis, Biliary / Q000201:enzymology / Q000276:immunology* / Q000628:therapy*; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000276:immunology; D011768:Pyruvate Dehydrogenase Complex / Q000008:administration & dosage / Q000276:immunology*
D001324:Autoantigens; D011768:Pyruvate Dehydrogenase Complex