Graves’ hyperthyroidism and thyroiditis in HLA-DRB1*0301 (DR3) transgenic mice after immunization with thyrotropin receptor DNA
| Autor: | Alvaro A. Giraldo, Chella S. David, Wei Zen Wei, Yi-chi M. Kong, J. P. Banga, M. Gora, P. V. Rao, G. Alsharabi, Jeffrey C. Flynn |
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| Rok vydání: | 2003 |
| Předmět: |
Male
endocrine system medicine.medical_specialty endocrine system diseases Graves' disease medicine.medical_treatment Transgene Immunology Mice Transgenic Thyroiditis Thyrotropin receptor Mice Cardiotoxin Mice Inbred NOD Internal medicine Vaccines DNA medicine Animals Immunology and Allergy Genetic Predisposition to Disease Autoantibodies NOD mice business.industry Thyroid Thyroiditis Autoimmune Receptors Thyrotropin HLA-DR Antigens medicine.disease Graves Disease Disease Models Animal Endocrinology medicine.anatomical_structure Animal Studies Female Thyroglobulin business HLA-DRB1 Chains |
| Zdroj: | Clinical and Experimental Immunology. 135:35-40 |
| ISSN: | 1365-2249 0009-9104 |
| DOI: | 10.1111/j.1365-2249.2004.02333.x |
| Popis: | SUMMARY Familial and twin studies in Caucasians have established that the MHC class II allele HLA-DRB1*0301 (DR3) is a strong susceptibility gene in Graves’ hyperthyroid disease (GD). To determine if a DR3 transgene could help establish an animal model for GD, we expressed DR3 molecules in class II-knockout NOD mice (H2Ag7–). DR3+g7– mice were given cardiotoxin prior to immunization on weeks 0, 3 and 6 with plasmid DNA encoding human thyrotropin receptor (TSHR). Two groups of mice were also coimmunized with plasmid DNA for IL-4 or GM-CSF. Serial bleeds on weeks 8, 11 and 14 showed that approximately 20% of mice produced thyroid-stimulating antibodies (Abs), and approximately 25% had elevated T4 levels. In particular, a subset displayed both signs of hyperthyroidism, resulting in approximately 30% with some aspect of GD syndrome. Additional mice had thyroid-stimulating blocking Abs and/or TSH-binding inhibitory immunoglobulins, while most mice showed strong labelling of TSHR+ cells by flow cytometry. Interestingly, lymphocytic infiltration with thyroid damage and Abs to mouse thyroglobulin were also noted. Vector controls were uniformly negative. Thus, DR3 transgenic mice can serve as a model for GD, similar to our earlier reports that this allele is permissive for the Hashimoto's thyroiditis model induced with human thyroglobulin. |
| Databáze: | OpenAIRE |
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