Elevated anti-α-galactosyl antibody titres. A marker of progression in autoimmune thyroid disorders and in endocrine ophthalmopathy?

Abstract

Abstract. The titres of anti-α-galactosyl antibodies were measured by passive haemagglutination in 50 control subjects and in 128 patients presenting with various thyroid disorders. Titres of control subjects ranged from 1/10 to 1/80, regardless of age and blood group. Elevated titres (> 1/80) were constantly noted in 6/6 patients with progressive exophthalmos, in 5/5 patients with untreated Graves' disease, and in 11/12 patients with progressive nontoxic goitre. By contrast, the titres were within the normal range in primary myxoedema (17 patients) and in residual exophthalmos (11 patients), whereas they were only erratically increased in 1/31 patients with treated or cured Graves' disease and in 5/36 patients with nonprogressive nontoxic goitre. Finally, elevated titres were also found in 3/7 patients presenting with autoimmune thyroiditis. No correlations could be established between elevated titres and the thyrotropin binding inhibiting immunoglobulin activity, the antithyroglobulin antibody titres or the antimicrosomal antibody titres. As in the control subjects, the anti-α-galactosyl antibodies mainly belonged to the IgG class. Affinity purified anti-α-galactosyl antibodies were capable of binding to trypsinized human and porcine thyroid cells in culture, as shown by indirect immunofluorescence. On the other hand, they were not able to react with untreated thyroid cells. The data show that the measurement of anti-α-galactosyl antibody titres could represent an easy and useful tool to determine whether an autoimmune thyroid disorder is in progression. Besides, they suggest that some of the antigenic determinants implicated in the enhanced production of anti-α-galactosyl antibodies are present, but normally hidden, within the cell surface of thyroid cells.

Reactivity of chagasic antigal antibodies with noninfected cells treated withTrypanosoma cruzi secreted/excreted antigens

“…These authors suggested that previous thyroid lesions could expose normally hidden antigenic determinants that would in turn enhance the antigal response, as described to occur after some renal injuries (32). Interestingly, the reactivity pattern of the antigal reactive human thyroid cells obtained by Etienne-Decerf (30) was dotted fluorescence on the cell surface similar to that observed by us in cells reactive with chagasic antigal (Fig. 3a).…”

“…These authors suggested that antigal antibodies may be implicated in the elimination of "altered" human red blood cells. Etienne-Decerf (30) showed that 30% of human thyroid cells, obtained from thyroid primary cultures and treated in vitro with exogenous trypsin, reacted with antigal antibodies. These authors suggested that previous thyroid lesions could expose normally hidden antigenic determinants that would in turn enhance the antigal response, as described to occur after some renal injuries (32).…”

Human natural anti-Gal IgG regulates alternative complement pathway activation on bacterial surfaces.

“…Anti-Gal's blocking ofACP activation may serve to protect man from continuous activation of complement on the surface ofthese and potentially other senescent human cells. Conversely, anti-Gal appears to play a detrimental role in the pathogenesis of certain autoimmune disorders, including thyroiditis, IgA nephropathy, and HenochShoenlein purpura (16,47). Our findings suggest that anti-Gal also may play a role in the intravascular survival of certain Gram-negative bacteria and raise intriguing questions about the effect ofthis ubiquitous molecule on other immune effector mechanisms, including opsonophagocytosis and T and B cellmediated events.…”

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

“…Such antibodies mimic the effect of TSH and continuously stimulate the metabolic activity of thyroid cells, leading to enlargement of the thyroid and hyperactivity of the gland (thyrotoxicosis). Anti-Gal titers were found to be markedly elevated in such patients [24], possibly as a result of the aberrant expression of ~-galactosyl epitopes on autologous thyroid cells. Furthermore, if these epitopes are expressed on the TSH receptor glycoprotein molecules, one could predict that the binding of anti-Gal would result in a stimulatory TSH-like effect.…”

“…Analysis of the anti-Gal isotypes in the serum was performed using specific anti-isotype antibodies [16,24,32,68]. These studies have indicated that most of the anti-Gal reactivity in the serum is of IgG class.…”