Mitochondrial antibodies in primary biliary cirrhosis. I. Localization of the antigen to mitochondrial membranes.

The antigen reacting with complement-fixing antibodies in the sera of patients with primary biliary cirrhosis was localized predominantly in the mitochondrial fraction of tissue homogenates obtained by differential centrifugation. Purified mitochondrial preparations had a high content of the antigen whereas purified lysosomes failed to fix complement with PBC sera. Analysis of a number of fractionation experiments showed a high correlation between antigen content and the mitochondrial enzyme succinic dehydrogenase in all fractions.

The release of thyroglobulin from the thyroid gland into thyroid lymphatics; the identification of thyroglobulin in the thyroid lymph and in the blood of monkeys by physical and immunological methods and its estimation by radioimmunoassay.

The iodoprotein which was found in the lymph draining from the thyroid gland of monkeys has been identified as thyroglobulin, both by physical and by immunological techniques. A sensitive and highly specific radioimmunoassay was developed by which thyroglobulin has been estimated in the thyroid lymph and in the blood of these animals. Small but appreciable concentrations of thyroglobulin were found in thyroid venous and in peripheral blood.

Tissue antibodies in primary biliary cirrhosis, active chronic (lupoid) hepatitis, cryptogenic cirrhosis and other liver diseases and their clinical implications.

The sera of virtually all patients with primary biliary cirrhosis contained non-organ specific antibodies, probably directed against mitochondria, which give rise to cytoplasmic `M' immunofluorescence in unfixed sections from various organs in high titres. They were also found in 31% of patients with cryptogenic cirrhosis particularly those with obstructive features, and 28% of cases of active chronic (lupoid) hepatitis. In contrast only two patients out of twenty-eight with extrahepatic biliary obstruction and one patient out of twenty-five with infective hepatitis gave positive reactions and then in very low titre.

The activity of different fractions of homologous thyroid extract in the production of allergic thyroiditis in the rat.

Rat thyroglobulin with a high degree of ultracentrifugal purity can be obtained by zone ultracentrifugation of crude thyroid extracts. The thyroglobulin fraction was even more effective than the original extract as an antigen for the production of experimental allergic thyroiditis. Material in the extracts with lower sedimentation coefficients than thyroglobulin were ineffective as antigens in this respect as was a homologous thyroid microsomal fraction.

THE ENHANCEMENT OF 19S ANTIBODY PRODUCTION BY PARTICULATE ANTIGEN.

Injection of human thyroglobulin solution into rabbits gave rise to a transient 19S antibody response which could however be maintained by repeated administration of antigen. When the antigen was coated onto acrylic resin particles, the titre of 19S antibodies was increased nearly 20-fold whereas 7S antibody levels were unchanged. This selective enhancement of 19S antibody synthesis by particulate antigen was also seen using human gamma-globulin.

CHARACTERIZATION OF THE HUMAN GASTRIC PARIETAL CELL AUTO-ANTIGEN.

The gastric parietal cell auto-antigen is localized essentially in the microsomal fraction of mucosal homogenates obtained by centrifugation over a sucrose density gradient. The fractionation is facilitated by digestion of gastric mucus with ficin before disruption of the tissue. The antigen was assayed by a quantitative complement-fixation method.

THE CYTOPLASMIC AUTO-ANTIGEN OF THE HUMAN THYROID. I. IMMUNOLOGICAL AND BIOCHEMICAL CHARACTERISTICS.

The reaction between the thyroid microsomal antigen and Hashimoto sera was studied by quantitative complement-fixation. Iso-fixation curves indicated a heterogeneity among individual sera and cross-absorption experiments suggested that this could be attributed to antibodies with differing abilities to fix complement with the same antigenic determinants. The results of equilibrium density gradient centrifugation, electron microscopic and immunofluorescent studies were consistent with an association of the antigen with small smooth-surfaced vesicles in the microsomal fractions.