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From the Department of Microbiology and The Center for Immunology, State University of New York at Buffalo, Buffalo, New York, Department of Immunology and Microbiology, Wayne State University, Detroit, Michigan and Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut
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.
Footnotes
1 This study was supported by United States Public Health Service Grant CA-02357 from the National Cancer Institute, National Institutes of Health, and Contracts No. 1-HD-2841 and 72-2775 from the National Institute of Child Health and Human Development, National Institutes of Health.
2 Present address: Department of Pathology, Royal College of Surgeons, Lincoln's Inn Fields, London, England.
3 Recipient of Public Health Service Career Development Award AI-00082.
4 Reprint requests should be addressed to: Pierluigi E. Bigazzi, M.D., Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut 06032.
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