Graves' disease as a model for anti-Gal involvement in autoimmune diseases.

Abstract

Anti-Gal, which is the most abundant antibody in humans appeared relatively recently in the evolution of Old World monkeys and apes, i.e., approximately 20 million years ago, subsequent to the suppression of α-gal epitope expression (Galili et al., 1988; see the chapter of Galili on the “Evolution of α1,3galactosyltransferase and of the α-gal epitope” in this book). It is well established that humans do not produce α-gal epitopes because they lack the glycosylation enzyme α1,3galacto-syltransferase (α1,3GT). This enzyme synthesizes α-gal epitopes on glycolipids and glycoproteins in nonprimate mammals and New World monkeys (Galili et al., 1987a; 1988; Spiro and Bhyroo 1984; Thall et al., 1991). Nevertheless, several studies have described the in vitro interaction of anti-Gal with various human cells. These included binding of the antibody to: placental cells (Christiane et al., 1992), the mammary carcinoma cell line MCF7 (Galili 1989; Petriniyak et al., 1991), freshly obtained mammary carcinoma cells (Castronovo et al., 1989), human normal senescent red cells (Galili et al., 1986), and some pathologic red cells including red cells from patients with β-thalassemia (Galili et al., 1983; 1984) and sickle cell anemia (Galili et al., 1986). Other studies demonstrated marked increase in antiGal activity in patients with autoimmune diseases such as Graves’ Disease (Etienne-Decerf et al., 1987) and scleroderma (Gabrielli et al., 1991). Taken together, all these observations suggest that despite the evolutionary suppression of α-gal epitope expression in ancestral Old World primates, anti-Gal may interact with human cells under certain circumstances, which are poorly understood at present.