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Studies of Human Intrinsic Factor Auto-Antibodies¹

From the Gastroenterology Unit, Department of Medicine, University of Rochester School of Medicine, Rochester, New York, and the Division of Haematology, The Toronto General Hospital, Toronto, Canada

Abstract

1. A study of the sera of 19 patients with pernicious anemia by radioimmunodiffusion, by a charcoal adsorption assay and by gel filtration with Sephadex G100, showed conclusive evidence for the occurrence of two types of antibody to human intrinsic factor in the serum of some of these patients.

2. One type of antibody, the "blocking" antibody, detected by the charcoal adsorption assay, reacted with intrinsic factor to prevent subsequent formation of the B₁₂-intrinsic factor complex. Blocking antibody was unable to react with preformed intrinsic factor-B₁₂ complex.

3. The second type of antibody, "binding" antibody, was shown to react either with the intrinsic factor itself or with the intrinsic factor-B₁₂ complex. Although this antibody reacted with intrinsic factor alone, it did not prevent the subsequent combination of intrinsic factor with vitamin B₁₂ which occurred without displacement of the antibody by the B₁₂.

4. Of the 19 sera studied, eight showed the presence of both antibodies, in two the blocking antibody only was detected, and in one only the binding antibody. The antibodies varied in amount independently of one another. From the small number of patients studied, it did not appear that one occurred much more frequently than the other, and there was no obvious correlation between the presence of antibodies and the age of the patient or the duration of the disease.

5. Instrinsic factor which had formed a complex with the binding antibody could still react with the blocking antibody. This reaction occurred without displacement of the binding antibody, indicating that the intrinsic factor molecule has two distinct antigenically reactive sites.

Footnotes

¹ Supported by grants from the Monroe County Cancer and Leukemia Association and from the National Institutes of Health (CA-09546 and AM-08956).