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

Thall, Aron; Etienne-Decerf, J; Winand, René; Galili, Uri

doi:10.3109/08916939109004811

Cited by 11 publications

(5 citation statements)

References 25 publications

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“…Previous studies using porcine hepatocytes treated with α‐galactosidase eliminated the binding of anti‐α‐gal antibodies as well as complement‐mediated lysis of the cells [22,45–47]. However, living xenograft tissues have the potential for constant turnover of membranous proteins resulting in the reappearance of α‐gal epitope within 24 h [22].…”

Section: Discussionmentioning

confidence: 99%

Immunologic analyses of bovine bone treated with a novel tissue sterilization process

Supronowicz

Zhukauskas

York-Ely

et al. 2008

Xenotransplantation

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Section: Discussionmentioning

confidence: 99%

Immunologic analyses of bovine bone treated with a novel tissue sterilization process

Supronowicz

Zhukauskas

York-Ely

et al. 2008

Xenotransplantation

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“…The mechanisms underlying the specific stimulatory effect of anti-Gal on Graves' disease thyroid cells is not understood as yet, but studies on the structure and expression of the ~I,3GT gene and of other glycosyltransferase genes in these patients may contribute to the understanding of this phenomenon. It is of interest to note that using a highly sensitive radioimmunoassay, we have demonstrated that normal human thyroid cells, like normal red cells, express small amounts of ~-galactosyl epitopes, which apparently are not accessible in vivo to anti-Gal [82]. It may be possible that ~-galactosyl epitopes expression in Graves' disease thyroid cells is modulated so that the epitope becomes accessible to interaction with anti-Gal.…”

Section: Anti-gal and Autoimmune Diseasesmentioning

confidence: 99%

Evolution and pathophysiology of the human natural anti-?-galactosyl IgG (anti-Gal) antibody

Galili

1993

Springer Semin Immunopathol

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180

132

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Anti-Gal is a human natural antibody which interacts specifically with the mammalian carbohydrate structure Gal alpha 1-3Gal beta 1-4GlcNAc-R, termed, the alpha-galactosyl epitope. This antibody constitutes approximately 1% of circulating IgG in human serum and is produced, upon stimulation, by 1% of circulating B lymphocytes. Anti-Gal is also present as IgA antibodies in body secretions such as saliva, milk and colostrum. The antigenic source for the constant production of anti-Gal seems to be the alpha-galactosyl-like epitopes found on many bacteria of the gastrointestinal flora. Whereas anti-Gal is abundant in humans, apes and Old World monkeys, it is absent from New World monkeys, prosimians and nonprimate mammals. The latter group of species produces, however, large amounts of alpha-galactosyl epitopes (> 10(6) epitopes per cell). It is estimated that anti-Gal appeared in ancestral Old World primates less than 28 million years ago, possibly as a result of an evolutionary event which exerted a selective pressure for the suppression of alpha-galactosyl epitopes expression by inactivation of the gene for the enzyme alpha 1,3 galactosyltransferase. This also resulted in the loss of immune tolerance to the alpha-galactosyl epitope and the production of anti-Gal. The physiologic role of this antibody is not clear as yet. It may participate in the protection against gastrointestinal bacteria. In addition it seems to contribute to the removal of normal and pathologically senescent red cells by interacting with the few hundred cryptic alpha-galactosyl epitopes which are exposed de novo in the course of red cell aging, thereby opsonizing these cells for phagocytosis by reticuloendothelial macrophages. The alpha-galactosyl epitope has been found to be aberrantly expressed on human cells and the interaction of anti-Gal with such epitopes may result in autoimmune disease. Preliminary data suggest such a mechanism in Graves' disease. Anti-Gal has been found to interact with therapeutic recombinant proteins expressing alpha-galactosyl epitopes, but so far there is no indication that it affects the half-life in the circulation and the biologic activity. Detection of anti-Gal in the seminal fluid and in the cerebrospinal fluid may serve as a simple means for assessment of damage to the blood-genital tract barrier or the blood-brain barrier. Studies on the interaction of anti-Gal with aberrantly expressed alpha-galactosyl epitopes on human cells may elucidate the possible role of anti-Gal in human autoimmune diseases.

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“…Anti-Gal constitutes as much as 1% of circulating total IgG, and 1-4% of total IgM in human sera (2)(3)(4). Although the physiological significance of antiGal is not entirely clear as yet, it has been implicated in autoimmune disease and tumor immunity (5)(6)(7). In addition, anti-Gal Abs are a major barrier to xenotransplantation of pig organs into humans, because hyperacute rejection is initiated by their binding to Gal determinants that are abundantly expressed on porcine endothelial cell glycoproteins and glycolipids (8 -11).…”

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confidence: 99%

Mac-1-Negative B-1b Phenotype of Natural Antibody-Producing Cells, Including Those Responding to Galα1,3Gal Epitopes in α1,3-Galactosyltransferase-Deficient Mice

Ohdan

Swenson

Gray³

et al. 2000

The Journal of Immunology

119

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Human natural Abs against Galα1-3Galβ1-4GlcNAc (Gal) epitopes are a major barrier to xenotransplantation. Studies in this report, which use combined multiparameter flow cytometric sorting and enzyme-linked immunospot assay, demonstrate that anti-Gal IgM-producing cells are found exclusively in a small B cell subpopulation (i.e., CD21−/low IgMhigh B220low CD5− Mac-1− 493− cells) in the spleens of α1,3-galactosyltransferase-deficient mice. All IgM-producing cells were detected in a similar splenic subpopulation of α1,3-galactosyltransferase-deficient and wild-type mice. A higher frequency of B cells with anti-Gal surface IgM receptors was observed in the peritoneal cavity than in the spleen, but these did not actively secrete Abs, and showed phenotypic properties of B-1b cells (CD21−/low IgMhigh CD5− CD43+ Mac-1+). However, these became Mac-1− and developed anti-Gal Ab-producing activity after in vitro culture with LPS. The splenic B cells with anti-Gal receptors consisted of both Mac-1+ B-1b cells and Mac-1− B-1b-like cells. The latter comprised most anti-Gal IgM-producing cells. Our studies indicate that anti-Gal natural IgM Abs are produced by a B1b-like, Mac-1− splenic B cell population and not by plasma cells or B-1a cells. They are consistent with a model whereby B-1b cells lose Mac-1 expression upon Ag exposure and that these, rather than plasma cells, become the major IgM Ab-producing cell population.

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

Cited by 11 publications

References 25 publications

Immunologic analyses of bovine bone treated with a novel tissue sterilization process

Immunologic analyses of bovine bone treated with a novel tissue sterilization process

Evolution and pathophysiology of the human natural anti-?-galactosyl IgG (anti-Gal) antibody

Mac-1-Negative B-1b Phenotype of Natural Antibody-Producing Cells, Including Those Responding to Galα1,3Gal Epitopes in α1,3-Galactosyltransferase-Deficient Mice

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