2 Humoral Immunity in Graves' Disease J. M. McKENZIE M.ZAKARIJA A. SATO

Humoral immunity in Graves' disease has been recognized for about 20 years. Initially antibodies to thyroglobulin and to other components of the thyroid gland were detected by insensitive assay techniques such as precipitation in agar; subsequently more quantitative procedures were developed and these showed that in Graves' disease, in comparison with findings in Hashimoto's disease, high titres of antibody to the thyroid microsomal antigen, rather than to thyroglobulin, were to be expected (Roitt and Doniach, 1959). In fact, these original data have to be re-evaluated in the light of more recent findings. The relative sensitivities of the most commonly used earlier assays (a tanned red cell haemagglutination test for antithyroglobulin and a complement-fixation test for the antibody to the thyroid microsomal antigen) were such as strongly to favour detection of antithyroglobulin. Since 1973 tanned red cell techniques for both antibodies (developed by the Fujizoki Co. of Japan) have become progressively more commonly used, and with these kits there is a much improved sensitivity for detecting the antibody to the thyroid microsomal antigen; in our experience comparing Graves' and Hashimoto's diseases, there is now little difference in either the incidence or titre of antibody to microsomal antigen and in both conditions antibody to thyroglobulin, though not uncommon, is found less frequently. This conclusion may be drawn also from data reported by Amino et al (1976) (Figure 1) who used tanned red blood cell agglutination techniques, and from the earlier findings of Mori and Kriss (1971) who developed competitive binding radioimmunoassays for these antibodies. By other techniques, especially immunofluorescence, antibodies to additional antigens have been described; these have included organ nonspecific antibodies to nuclear and mitochondrial antigens and, with undue frequency, antibodies to other organ-systems, e.g. to gastric parietal cells and to intrinsic factor. It appears that antibodies to organ non-specific antigens reflect the general autoimmune trait of such patients and those to other organ systems indicate the possible coexistence of associated autoimmune disease, e.g. pernicious anaemia in the case of antibodies to Clinics ill Endocrinology and Metabolism - Vol. 7, No.1, March 1978.

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J. M. McKENZIE. M. ZAKARIJA AND A. SATO

intrinsic factor or gastric parietal cells. However, regarding the anti-thyroid antibodies described above, there is now general consensus that they are not pathogenetic but merely indicative of an underlying autoimmune thyroid disease. It remains undecided what level of these antibodies in Graves' disease ought to be taken as diagnostic of coexistent Hashimoto's disease; that the two conditions may occur simultaneously is accepted and it is possible that co-development of the two diseases occurs in the majority of patients with Graves' disease. 163.840

81.920 40,9&0 20.480 10,240

~

5120

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r-

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zc

z =l

Table 1. Assays of thyroid-stimulating antibody: methods using preparations of human thyroid

No.

Reference

Acronym

Nilme

Method

Onaya et ill (1973)

HTS

Human thyroid stimulator

Colloid droplet formation or increase in cyclicAMP concentration in human thyroid slices (10 min incubation) Stimulation of adenylate cyclasein human thyroid membranes Increase in cyclicAMP concentration in human thyroid slices (2 hr incubation) Binding to human thyroid, preventing ('protecting ') subsequent binding of LATS Competition with thyrotrophin in thyrotrophinreceptor assay using human thyroid membranes

Orgiazzi et 011 (1976)

H·TACS

III

McKenzie and Zakarija (1977)

TSAb

IV

Adams and Kennedy (1967)

LATS-P

Smith and Hall (1974)

TSI

II

Human thyroid adenyl cyclasestimulator Thyroid-stimulating antibody Long-acting thyroid stimulator-protector

V

Thyroid-stimulating immunoglobulins

"