The study of the Ig variable region heavy chain (VH) genes used to encode antibodies specific for self-epitopes from murine hybridomas showed that three VH families are primarily utilized: VH J558, the largest family, and VH QPC52 and VH 7183, the families most proximal to the Ig joinin region heavy chain genes. These monoclonal autoantibodies express cross-reactive idiotopes shared by rheumatoid factors and antibodies specific for Sm. The expression of these idiotypes is independent of major histocompatibility complex and Ig constant region heavy chain haplotypes, self-antigen specificity, and even the VH gene family utilized.Though the experiments described here are limited to murine autoantibodies, similarities exist between murine and human autoimmune diseases. Studies that ain to investigate the relationship between VH gene expression and the presence of crossreactive idiotypes among human autoantibodies should enable us to better understand the mechanisms of autoimmunity and self-tolerance.

Thyroglobulin antibodies (TgAbs) are typically found in autoimmune thyroid diseases and, more rarely, in nonautoimmune thyroid diseases and healthy subjects. To determine whether TgAbs associated with different conditions recognize different epitopes on the thyroglobulin molecule, we studied 28 patients with Hashimoto's thyroiditis, 30 with Graves' disease, 21 with thyroid carcinoma, 18 with nontoxic goiter, and 25 healthy subjects. All patients were selected for the presence of TgAbs; 4/25 healthy subjects also had TgAbs. The sera were assayed for the their ability to inhibit the binding of monoclonal antibodies to thyroglobulin in an ELISA assay. We found that: 1) TgAbs in Hashimoto's patients preferentially recognized three clusters of epitopes (II, III and typically VI), with no difference between the goitrous and the atrophic variants; 2) TgAbs in Graves' patients were directed toward cluster II, with no difference between the presence or the absence of ophthalmopathy; 3) TgAbs in thyroid carcinoma patients recognized the same clusters as Hashimoto's patients; 4) TgAbs in nontoxic goiter patients and in the four healthy subjects showed no restriction in epitope recognition. We suggest that in individuals with no overt clinical or biochemical thyroid abnormalities but with TgAbs, the finding that these TgAbs recognize particular immunodominant clusters may be utilized to predict full-blown thyroid disorders. Longitudinal studies are needed to evaluate the possible clinical application of this methodology.

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SUMMARYThe IgG subclass distribution of thyroglobulin antibodies (TgAb) has been studied in Hashimoto and Graves' patients by several investigators with conflicting results, in part explainable by methodological problems. We have recently developed a quantitative ELISA to measure in absolute terms the serum concentration of TgAb subclasses. The aim of the present study was to apply this method in a large series of patients with autoimmune as well as, for the first time, non-autoimmune thyroid diseases. We examined 28 patients with Hashimoto's thyroiditis, 30 with Graves' disease, 21 with thyroid carcinoma and 18 with non-toxic goitre, all selected for the presence of TgAbs. The results indicated that TgAbs in thyroid diseases were not restricted to any particular isotype, but comprised all four IgG subclasses. IgGI was represented similarly in the four groups. The same was true for IgG3, even though its contribution to the total antibody content was very small. IgG4 was the dominant subclass in patients with Graves' disease, thyroid carcinoma and non-toxic goitre, probably reflecting a prolonged antigenic challenge. In Hashimoto's thyroiditis IgG2 was dominant, possibly because T helper lymphocytes infiltrating the thyroid are typically Thl type.

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