Thyroid Antibodies in Spontaneous Autoimmune Thyroiditis in the Buffalo Rat

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Abstract
Thyroid antibodies in the sera of BUF rats are closely correlated with spontaneous thyroiditis; their detection may facilitate the study of this animal model of organspecific autoimmunity. In a group of 115 retired BUF breeders (females older than 1 year), 26% had mononuclear cell infiltration of the thyroid and high titers of thyroid antibodies detectable by indirect immunofluorescence (IF) and chromic chloride passive hemagglutination (CCH). In contrast, low-titered thyroid antibodies were present in 9% of the rats that had normal thyroids. Sequential studies performed on a group of 76 neonatally thymectomized BUF rats showed that at 2 months 24% had high titers of thyroid antibodies detectable by IF and 8% by CCH and at 3 months these percentages increased to 27% by IF and 25% by CCH. When the rats were sacrificed at 4 months, at a time when spontaneous disease is not seen in untreated animals, 26% were found to have mononuclear cell infiltration of their thyroids. Approximately 75% of these rats with thyroiditis had been positive for thyroid antibodies at 2 months and 90% at 3 months. At sacrifice all of these animals had high-titered antibodies to thyroid antigens. In contrast, low-titered thyroid antibodies were present in 36% of the animals without thyroiditis. Intravenous injection of BUF thymus cells into neonatally thymectomized rats failed to reduce the incidence of thyroiditis and thyroid antibodies. Approximately 33% of these animals had both thyroid infiltration and serum antibodies, whereas 19% of those with normal thyroids had low-titered thyroid antibodies. Titers of circulating thyroid antibodies were closely correlated with the initial and intermediate stages of thyroiditis, i.e., animals with less infiltration had the lowest titers, whereas animals with intermediate levels of infiltration had high antibody titers. On the other hand, rats with a high degree of thyroid infiltration had relatively lower titers of thyroid antibodies. Direct IF of infiltrated thyroids revealed the presence of rat immunoglobulins in these organs, suggesting a possible direct or indirect role of autoantibodies in the pathogenesis of the disease. We attempted to detect delayed hypersensitivity by skin testing with thyroid antigens and observing reactions at 4, 24, and 48 hr. All of 123 rats were negative, 20% of which had thyroiditis and thyroid antibodies. No serum MIF activity was detected in rats with thyroiditis and those with normal thyroids. The absence of delayed hypersensitivity reactions in these experiments provides further support for the contention that spontaneous thyroiditis in the BUF rat may be antibody mediated.