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Immunologic Comparison of Human Adult Thyroglobulin to Other Primate Adult and Human Fetal Thyroglobulins¹

From the Departments of Microbiology and Anatomy, Wayne State University College of Medicine, Detroit, Michigan

Abstract

1. Using human autoantibodies and rabbit and chicken heteroantibodies to adult human thyroglobulin, thyroid extracts from man, chimpanzees, old world monkeys, new world monkeys, pottos and nonprimate mammals were compared in Wilson modified Ouchterlony plates. Cross-reactions decreased as phylogenetic distance from man increased, with the decrease of cross-reaction being much greater for the human autoantibodies than for the rabbit or chicken antibodies on going from old world monkeys to more distant relatives. Thus, the less species-specific determinants on human thyroglobulin do not appear to be as autoantigenic as the more species-specific determinants.

2. Adult human thyroid extract was also compared to 40 fetal thyroid extracts encompassing a broad range of gestational ages. Thyroglobulin was detected in most fetuses from 12 through 16 weeks' gestation and in all fetuses after 16 weeks. The quantity of thyroglobulin per milligram of extract protein was much smaller in early fetal thyroids than in late fetal and postnatal thyroids.

3. Fetal thyroglobulin showed the same species specificity and antigenic specificity as adult thyroglobulin.

4. A typical extract, whether from a fetal or postnatal gland, contained at least two types of saline soluble molecules with autoantigenic determinants. The more species-specific determinants, to which the majority of the autoantibodies were directed, were found on one type but not on the other.

5. It is hypothesized that the less species-specific determinants predominate on a thyroglobulin fraction which more frequently gains access to the blood circulation than the thyroglobulin fraction with the more species-specific determinants. Thus a greater degree of immunologic tolerance or paralysis would develop to the less species-specific determinants than to the more species-specific determinants.

Footnotes

¹ This investigation was supported by Grants MH-02476 of the National Institutes of Health and 226 of the National Multiple Sclerosis Society with summer fellowships from the Lederle Laboratories and the National Science Foundation.

² Present address: Children's Hospital, 3700 California Street, San Francisco, California.