TRANSIENT NEONATAL-HYPOTHYROIDISM - CHARACTERIZATION OF MATERNAL ANTIBODIES TO THE THYROTROPIN RECEPTOR

Transient neonatal thyroid disease is known to occur as a result of transplacental passage of maternal immu-noglobulin G (IgG) that contains antibodies to the TSH receptor (TRAb). Thyroid-stimulating antibody (TSAb) produces hyper-thyroidism, and antibody that blocks TSH binding (TBIAb) results in hypothyroidism. We have analyzed in detail the IgG from four women who gave birth to children with transient neonatal hypothyroidism and have shown stimulating and inhibiting antibodies to coexist in three. Human and/or rat thyroid (FRTL5) cells were used to show stimulatory effects in vitro. Inhibition was assessed as prevention of stimulation of these cells (by TSH or TSAb) or by the blocking of binding of [125I] TSH to its receptor. The IgG from two mothers was tested to identify whether the inhibitory and stimulating bioactivities resided in molecules characterized by either or both κ- or λ-light chains. Evidence for restricted heterogeneity (implying oligo-clonality) was obtained, in that with one, purely inhibitory IgG all activity was with IgGκ. With the other, stimulating and inhibitory activities were predominantly in IgGκ and IgGλ, respectively. In addition, the latter IgG contained a second stimulator that was not suppressed by either its own or other inhibitory IgG. Despite the presence of stimulatory antibodies in these IgG, the clinical effect was neonatal hypothyroidism, reflecting the greater potency of the inhibitory IgG in all instances. Based on the histories of these four women and their offspring it is apparent that TRAb, and in particular TBIAb, can develop at any point in the course of autoimmune thyroid disease, i.e. either at the onset or long after the autoimmune process has been established. © 1990 by The Endocrine Society.