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*
IRIBHN, ULB,
Euroscreen s.a., and
Laboratory of Histology, Louvain Medical School, Brussels, Belgium; and
§
Department of Pathology, University of Wales College of Medicine, Cardiff, Wales, United Kingdom
The generation of Abs recognizing the native structure of the human thyrotropin receptor (hTSHR) has been difficult because there is currently no method allowing the purification of correctly folded Ag in the amounts required by classical immunization protocols. The majority of Abs made against the hTSHR react preferentially with denatured molecules. We report that a humoral response against the native hTSHR, compatible with mAb production, is elicited in mice by immunization with a DNA construct encoding the receptor. BALB/c mice were inoculated in the anterior tibialis muscle with 100 µg of plasmid DNA harboring the hTSHR cDNA. Eleven weeks after the first injection, 10 mice of 14 showed by FACS analysis a strong IgG response against the hTSHR expressed at the surface of Chinese hamster ovary cells. A clear TSH-binding inhibiting Ig and thyrotropin-blocking Ab activity (competition with TSH binding and TSH activity, respectively) was demonstrated in the majority of sera tested. One serum exhibited a clear stimulating activity. Despite the maintenance of normal circulating free T4 levels in all mice, these bioactivities persisted until 18 wk, in which mice were sacrificed, their thyroids were examined histologically, and spleens from two animals were used for mAb production. All mice displayed a severe lymphocytic infiltration of their thyroids, composed mostly of activated B cells. Three mAbs were produced against conformational epitopes of the hTSHR. We conclude that genetic immunization is an efficient method of generating Abs recognizing the native structure of the hTSHR and a new way of inducing thyroiditis in mice murine.
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J. Pohlenz, L. Duprez, R. E. Weiss, G. Vassart, S. Refetoff, and S. Costagliola Failure of Membrane Targeting Causes the Functional Defect of Two Mutant Sodium Iodide Symporters J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2366 - 2369. [Abstract] [Full Text]
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M. Tonacchera, P. Agretti, A. Pinchera, V. Rosellini, A. Perri, P. Collecchi, P. Vitti, and L. Chiovato Congenital Hypothyroidism with Impaired Thyroid Response to Thyrotropin (TSH) and Absent Circulating Thyroglobulin: Evidence for a New Inactivating Mutation of the TSH Receptor Gene J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1001 - 1008. [Abstract] [Full Text]
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S. Kaithamana, J. Fan, Y. Osuga, S.-G. Liang, and B. S. Prabhakar Induction of Experimental Autoimmune Graves' Disease in BALB/c Mice J. Immunol., November 1, 1999; 163(9): 5157 - 5164. [Abstract] [Full Text] [PDF]
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J. C. Jaume, J. Guo, Y. Wang, B. Rapoport, and S. M. McLachlan Cellular Thyroid Peroxidase (TPO), Unlike Purified TPO and Adjuvant, Induces Antibodies in Mice That Resemble Autoantibodies in Human Autoimmune Thyroid Disease J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1651 - 1657. [Abstract] [Full Text]
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M.-C. Many, S. Costagliola, M. Detrait, J.-F. Denef, G. Vassart, and M. Ludgate Development of an Animal Model of Autoimmune Thyroid Eye Disease J. Immunol., April 15, 1999; 162(8): 4966 - 4974. [Abstract] [Full Text] [PDF]
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M. Kita, L. Ahmad, R. C. Marians, H. Vlase, P. Unger, P. N. Graves, and T. F. Davies Regulation and Transfer of a Murine Model of Thyrotropin Receptor Antibody Mediated Graves' Disease Endocrinology, March 1, 1999; 140(3): 1392 - 1398. [Abstract] [Full Text]
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S. Costagliola, N. G. Morgenthaler, R. Hoermann, K. Badenhoop, J. Struck, D. Freitag, S. Poertl, W. Weglöhner, J. M. Hollidt, B. Quadbeck, et al. Second Generation Assay for Thyrotropin Receptor Antibodies Has Superior Diagnostic Sensitivity for Graves' Disease J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 90 - 97. [Abstract] [Full Text]
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P. Rodien, C. Bremont, M.-L. R. Sanson, J. Parma, J. Van Sande, S. Costagliola, J.-P. Luton, G. Vassart, and L. Duprez Familial Gestational Hyperthyroidism Caused by a Mutant Thyrotropin Receptor Hypersensitive to Human Chorionic Gonadotropin N. Engl. J. Med., December 17, 1998; 339(25): 1823 - 1826. [Full Text] [PDF]
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B. Rapoport, G. D. Chazenbalk, J. C. Jaume, and S. M. McLachlan The Thyrotropin (TSH)-Releasing Hormone Receptor: Interaction with TSH and Autoantibodies Endocr. Rev., December 1, 1998; 19(6): 673 - 716. [Abstract] [Full Text]
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P. Rodien, F. Cetani, S. Costagliola, M. Tonacchera, L. Duprez, T. Minegishi, C. Govaerts, and G. Vassart Evidences for an Allelic Variant of the Human LC/CG Receptor rather than a Gene Duplication: Functional Comparison of Wild-Type and Variant Receptors J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4431 - 4434. [Abstract] [Full Text]
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C. Govaerts, A. Lefort, S. Costagliola, S. J. Wodak, J. A. Ballesteros, J. Van Sande, L. Pardo, and G. Vassart A Conserved Asn in Transmembrane Helix 7 Is an On/Off Switch in the Activation of the Thyrotropin Receptor J. Biol. Chem., June 15, 2001; 276(25): 22991 - 22999. [Abstract] [Full Text] [PDF]
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