As much as 1% of circulating
IgG in man (the natural anti-Gal antibody) is directed against the
alpha-galactosyl epitope, with the structure Gal alpha 1----3Gal beta 1----4GlcNAc-R. The
alpha-galactosyl epitope is abundantly expressed on cells of nonprimate mammals, prosimians, and New World monkeys. Its expression is diminished in Old World monkeys, apes, and humans. It has been previously suggested that interaction between anti-Gal and aberrantly expressed alpha-galactosyl
epitopes on thyroid cells may contribute to the initiation of autoimmune thyroid disorders. To study this possibility,
alpha-galactosyl epitope expression on thyroid cell membranes of normal individuals and patients with
Graves' disease was assessed by a sensitive radioimmunoassay. alpha-Gal-actosyl
epitopes were found both on normal and diseased thyroid cells. Whereas the concentration of these
epitopes on
Graves' disease thyroid membranes was somewhat higher than that observed in normal glands, the difference was not significant. The activity of the
enzyme, alpha 1-3-galactosyltransferase, which synthesizes the
alpha-galactosyl epitope, was higher in microsomal fractions obtained from some patients as compared with healthy controls, but not significantly different. In view of the abundance of anti-Gal antibody in the circulation, it is argued that, under physiologic conditions, the interaction of this antibody with alpha-galactosyl
epitopes does not elicit pathologic effects. However, aberrant expression of the
alpha-galactosyl epitope may result in effective anti-Gal binding to thyroid cells (e.g., rearrangement of this structure on the cell membrane or its increased expression).(ABSTRACT TRUNCATED AT 250 WORDS)