Immunologic studies with intrinsic factor in man.

Since the fundamental defect in pernicious anemia is inadequate or absent secretion of gastric intrinsic factor (1), specific therapy with intrinsic factor would seem, logically, to be the preferred treatment. After the demonstration (2, 3) that desiccated hog stomach could substitute for human gastric juice to facilitate the absorption of vitamin B12 in man, many patients with pernicious anemia were treated orally with extracts of hog pyloric mucosa and vitamin B12. In most cases, gratifying hematological improvement was noted initially. With continued administration of these preparations, however, a significant number of patients suffered hematologic relapse (4-9). In these individuals, it was found that sources of porcine intrinsic factor no longer facilitated vitamin B12 absorption (6-8, 10). This phenomenon of refractoriness to orally administered hog intrinsic factor concentrates (HIFC) was among the reasons that led the U.S.P. Anti-Anemia Preparations Advisory Board to recommend, in 1959, that such preparations be excluded from the U. S. Pharmacopoeia (11). Certain observations suggest that the refractory state is immunologic in origin. The present studies were undertaken in an attempt to demonstrate a causal relationship between immunization to HIFC and the refractory state, and have been previously reported in preliminary form (12).