Immunoglobulin G inhibitor of thyroid-stimulating antibody is a cause of delay in the onset of neonatal Graves' disease.
Studies were carried out with the serum IgG from a mother and her two children who developed neonatal Graves' disease several weeks after birth. The maternal IgG: (a) stimulated the human thyroid in vitro, but maximal stimulation was found only with dilution of the IgG; (b) was very potent in the long-acting thyroid stimulator (LATS)-protector assay, but only when an inhibitor of the system was diluted out; (c) inhibited a standard preparation of LATS in the mouse bioassay; (d) was biphasic in the thyrotropin-binding inhibition (TBI) assay, i.e., enhanced binding at low concentrations of IgG and inhibited binding at high levels. Enhancement in the TBI assay was found only with particulate preparations of human thyroid membranes as receptor and not when that material was solubilized, nor with guinea pig fat cell membranes as receptor. Serial blood samples from the second child were obtained at birth and until 3 mo of age. In the thyroid slice (cyclic AMP) assay system there was a negative dose-response relationship in testing IgG until age 45 d when it became positive, coinciding with the clinical recognition that hyperthyroidism had developed. The data are compatible with a concept that this mother's IgG contained thyroid-stimulating antibody (TSAb) and another moiety that inhibited TSAb through an action on the thyroid cell membrane, thus delaying the onset of hyperthyroidism in the neonate until the inhibiting IgG was metabolically cleared to an ineffective concentration.
D000818:Animals; D000906:Antibodies / Q000032:analysis; D001667:Binding, Competitive; D005260:Female; D006111:Graves Disease / Q000151:congenital / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000502:physiology*; D018828:Immunoglobulins, Thyroid-Stimulating; D007223:Infant; D007231:Infant, Newborn; D008135:Long-Acting Thyroid Stimulator / Q000032:analysis; D008566:Membranes / Q000378:metabolism; D051379:Mice; D013961:Thyroid Gland; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism
D000906:Antibodies; D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating; D013973:Thyrotropin-Releasing Hormone; D008135:Long-Acting Thyroid Stimulator