The α-Galactosyl Epitope on Human Normal and Autoimmune Thyroid Cells

Abstract

As much as 1% of circulating IgG in man (the natural anti-Gal antibody) is directed against the α-galactosyl epitope, with the structure Galαl→3Galβl→4GlcNAc-R. The α-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 α-galactosyl epitopes on thyroid cells may contribute to the initiation of autoimmune thyroid disorders. To study this possibility, α-galactosyl epitope expression on thyroid cell membranes of normal individuals and patients with Graves' disease was assessed by a sensitive radioimmunoassay. α-Galactosyl 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, αl-3-galactosyltransferase, which synthesizes the α-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 α-galactosyl epitopes does not elicit pathologic effects. However, aberrant expression of the α-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). Such an event may subsequently result in anti-Gal mediation of lesions which would contribute to the initiation of an autoimmune process within the thyroid gland.

Key Words:

• α-Galactosyl epitope
• thyroid
• anti-Gal antibody
• autoimmunity