Precipitating LKM antibodies in chronic liver disease (CLD)

LACK OF HAEMODYNAMIC EFFECT OF NALOXONE IN CIRRHOTIC PATIENTS AND RATS WITH BILIARY CIRRHOSIS S.S. Lee, A. Hadengue, R. Moreau, C. Girod, A. Braillon and D. Lebrec, Unit4 de Recherches de Physiopathologie H4patique, HSpital Beaujon, 92118 Clichy, France Much evidence suggests that endorphins mediate some of the circulatory derangements in endotoxemic and haemorrhagic shock. The patient with cirrhosis exhibits many similarities with the early shock state including a kyperkinetic systemic and splanchnic circulation manifested by increased cardiac output, decreased peripheral vascular resistance and splanchnic venous blood pooling. In addition, serum 8-endorphin levels have been found to be elevated in decompensated cirrhotic patients. Thus, in order to elucidate a possible pathogenic role for endorphins in the circulatory alterations of cirrhosis, we studied haemodynamic responses to naloxone, a pure endorphin antagonist, in patients with cirrhosis and in a rat model of biliary cirrhosis. Eight patients with alcoholic cirrhosis had measurements of cardiac output, mean arterial pressure, heart rate, forearm blood flow, hepatic venous pressure gradient, hepatic blood flow and azygos blood flow before and 30 min after an i.v. bolus of 3.2 mg naloxone. No significant haemodynamic changes were observed. In 8 rats rendered cirrhotic by ligation and section of the common bile duct and 8 sham-operated rats, injection of naloxone i mg/kg i.v. did not change cardiac output or portal tributary blood flow as measured by radioactive microspheres. These results suggest that, at least in the basal state, endorphins are not involved in mediating the circulatory derangements of cirrhosis.

PRECIPITATING LKM ANTIBODIES IN CHRONIC LIVER DISEASE (CLD). M. Lenzi, F. Cassani, M. Fusconi, U. Volta, F.B. Bianchi, E. Pisi. Istituto di Patologia Medica I, Universit~ di Bologna, Italy.

Liver Kidney Microsomal antibodies (LKM) are regarded as markers of a subgroup of autoimmune CLD. The LKM target antigen is located on the membranes of the endoplasmic reticulum but detailed information on its biochemical nature is lacking. 105 LKM positive sera from 25 patients (all except one suffering from CLD) were tested by double immunodiffusion and counterimmunoelectrophoresis against rat liver microsomal subfractions enriched in smooth (SER) and rough (HER) membranes both suspended in PBS (protein concentration i0 mg/ml). The purity of these fractions was assessed by RNA content which was 17.3 + 2 times (mean of 3 experiments SD) greater in RER than in SER. All sera tested with both techniques gave a precipitin line against the SER enriched fraction while no reaction could be demonstrated with RER. When the 105.000g supernatant of the SER fraction was tested, the precipitin reaction was unchanged~ demonstrating that the antigen is easily solubilized. Digestion experiments demonstrated that the reaction was abolished by trypsin treatment, while it was unaffected by DNAse and RNAse. None of the control sera (29 from patients with primary biliary cirrhosis, 9 with cryptogenic cirrhosis, 23 with autoimmune CLD and 20 blood donors) gave a positive reaction. Moreover no reaction could be demonstrated with 6 LKM2 positive sera from patients with chronic HDV infection. These data suggest that LKM positive sera contain precipitating antibodies directed against a protein which is easily extracted from the membranes of rat liver SER and that this antigen is not shared by LKM2 antibody described in chronic HDV infection.

$140