AN IMMUNOLOGIC BASIS FOR ACQUIRED RESISTANCE TO ORAL ADMINISTRATION OF HOG INTRINSIC FACTOR AND VITAMIN B12 IN PERNICIOUS ANEMIA*

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Abstract
Anti-bodies were produced in rabbits by injection of a hog gastric preparation with intrinsic-factor activity. The rabbit antiserum agglutinated erythrocytes to which hog intrinsic -factor concentrate had been bound with bis-diazotized benzidine. After absorption of this antiserum with nongastric hog protein, a fraction remained which agglutinated the coated erythrocytes and which could be neutralized only by hog gastric preparations with intrinsic-factor activity. This fraction was considered to contain "anti-intrinsic factor" antibodies. These antibodies did not react with human gastric juice, and when mixed with hog gastric preparations they inhibited the absorption of cyanocobalamin fed to nonrefractory patients with pernicious anemia, and altered the electrophoretic mobility of the cyanocobalamin-binding peak from the B to the gamma globulins. Sera obtained from patients with pernicious anemia with acquired resistance to oral therapy with hog intrinsic -factor concentrate were found to contain antibodies with the same immunologic properties as shown by the "anti-intrinsic factor" fraction of the rabbit antiserum. These data suggest that acquired resistance to oral therapy with hog intrinsic-factor concentrate in pernicious anemia is due to the formation of antibodies against intrinsic factor.