Penicillamine has an effect on immune complexes and immunoglobulins both in vivo and in vitro. We therefore studied the effect of penicillamine on immune complexes and immunoglobulins in primary biliary cirrhosis. Twenty-eight patients were randomly allocated into a treatment group receiving 600 to 900 mg of penicillamine, or a control group, and followed for a maximum of 24 months. After 12 and 24 months, serum immune complexes had fallen significantly in treated patients as compared to controls (P<0.05, P<0.01). Treatment reduced IgA, IgG and IgM concentrations, with IgM being significantly different from controls at six, 12 and 24 months (P<0.01). Over 24 months, serum aspartate transaminase levels fell in treated patients but rose in controls (P<0.01). Bilirubin concentrations increased at a slower rate in treated patients. Penicillamine may favorably influence the course of primary biliary cirrhosis by its immunologic action in addition to its copper-chelating action. (N Engl J Med 300:274–278,1979) PRIMARY biliary cirrhosis is a progressive fatal disease of unknown cause. Patients have clinical and serologic evidence of an altered immune state,1,2 and immune-complex activation of the complement system may play an important part in the destruction of intrahepatic bile ducts.3 Therapy with corticosteroids is contraindicated because of side effects, especially bone thinning,4 and no benefit has followed azathioprine.5 Primary biliary cirrhosis is complicated by marked hepatic copper accumulation, and since 1975 a controlled trial has been in progress at the Royal Free Hospital to assess the place of D-penicillamine therapy.6 Penicillamine also affects the immune system, and this action. © 1979, Massachusetts Medical Society. All rights reserved.
