Anke Schlüter1,2, Anja K Eckstein1,3, Alexandra Brenzel4, Mareike Horstmann1, Stephan Lang2, Utta Berchner-Pfannschmidt1, J Paul Banga1, Salvador Diaz-Cano5. 1. Molecular Ophthalmology, Department of Ophthalmology, University Hospital Essen, Essen, Germany. 2. Department of Oto-Rhino-Laryngology - Head and Neck Surgery, University Hospital Essen, Essen, Germany. 3. Department of Ophthalmology, University Hospital Essen, Essen, Germany. 4. Imaging Center Essen (IMCES), Institute for Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany. 5. Department of Histopathology, King's College Hospital NHS, London, United Kingdom.
Abstract
OBJECTIVES: Experimental models of Graves hyperthyroid disease accompanied by Graves orbitopathy (GO) can be efficiently induced in susceptible inbred strains of mice by immunization by electroporation of heterologous human TSH receptor (TSHR) A-subunit plasmid. The interrelated pathological findings in the thyroid glands of Graves disease (GD) that explain the core changes classically include diffuse follicular hyperplasia and multifocal mild lymphocytic infiltrate. However, the relative contributions of different thyroid tissue components (colloid, follicular cells, and stroma) have not been previously evaluated. In this study, we characterize the thyroid gland of an experimental mouse model of autoimmune GD. Our objective was to define the relative contribution of the different thyroid tissue components to the pathology of glands in the experimental model. METHODS: Mice were immunized with human TSHR A-subunit plasmid. Antibodies induced to human TSHR were pathogenic in vivo due to their cross-reactivity to mouse TSHR. RESULTS: Autoimmune thyroid disease in the model was characterized by histopathology of hyperplastic glands with large follicular cells. Further examination of thyroid glands of immunized animals revealed a significantly increased follicular area and follicle/stroma ratio, morphometrically correlated with a noninflammatory follicular hyperplasia/hypertrophy. The increased follicle/stroma ratio was the most relevant morphometrically variable summarizing the pathological changes for screening purposes. CONCLUSION: GD thyroid glands are enlarged and characterized by a noninflammatory diffuse follicular cell hyperplasia/hypertrophy and a significant increase in the follicles with an increased follicle/stroma ratio. Overall, this mouse model is a faithful model of an early hyperthyroid status of GD (diffuse glandular involvement and follicular expansion).
OBJECTIVES: Experimental models of Graves hyperthyroid disease accompanied by Graves orbitopathy (GO) can be efficiently induced in susceptible inbred strains of mice by immunization by electroporation of heterologous human TSH receptor (TSHR) A-subunit plasmid. The interrelated pathological findings in the thyroid glands of Graves disease (GD) that explain the core changes classically include diffuse follicular hyperplasia and multifocal mild lymphocytic infiltrate. However, the relative contributions of different thyroid tissue components (colloid, follicular cells, and stroma) have not been previously evaluated. In this study, we characterize the thyroid gland of an experimental mouse model of autoimmune GD. Our objective was to define the relative contribution of the different thyroid tissue components to the pathology of glands in the experimental model. METHODS: Mice were immunized with human TSHR A-subunit plasmid. Antibodies induced to human TSHR were pathogenic in vivo due to their cross-reactivity to mouse TSHR. RESULTS: Autoimmune thyroid disease in the model was characterized by histopathology of hyperplastic glands with large follicular cells. Further examination of thyroid glands of immunized animals revealed a significantly increased follicular area and follicle/stroma ratio, morphometrically correlated with a noninflammatory follicular hyperplasia/hypertrophy. The increased follicle/stroma ratio was the most relevant morphometrically variable summarizing the pathological changes for screening purposes. CONCLUSION: GD thyroid glands are enlarged and characterized by a noninflammatory diffuse follicular cell hyperplasia/hypertrophy and a significant increase in the follicles with an increased follicle/stroma ratio. Overall, this mouse model is a faithful model of an early hyperthyroid status of GD (diffuse glandular involvement and follicular expansion).
Authors: Sandra M McLachlan; Holly A Aliesky; Pavel N Pichurin; Chun-Rong Chen; Robert W Williams; Basil Rapoport Journal: Endocrinology Date: 2007-12-27 Impact factor: 4.736
Authors: Jeffrey C Flynn; Jacqueline A Gilbert; Chady Meroueh; Daniel P Snower; Chella S David; Yi-chi M Kong; J Paul Banga Journal: Immunology Date: 2007-05-29 Impact factor: 7.397