Evidence for a simplified view of autoantibody interactions with the thyrotropin receptor

Thyroid : Official Journal of the American Thyroid Association
L Schwarz-LauerBasil Rapoport

Abstract

Recently, many exceptions have been reported that undermine the concept that the epitopes for thyroid-stimulating autoantibodies (TSAb) and thyrotropin-blocking autoantibodies (TBAb) lie within the N-terminal and C-terminal portions of the thyrotropin receptor (TSHR) ectodomain, respectively. Here we have used a new approach to examine the issue by attempting to neutralize autoantibodies with the purified, N-terminal 289 amino acids of the TSHR ectodomain (TSHR-289), essentially the A subunit. Immunoglobulin G (IgG) with TSAb activity from 10 patients with Graves' disease was preincubated with or without purified active or inactive TSHR-289. Active, but not inactive, TSHR-289 completely neutralized TSAb activity in all sera. We then tested the ability of active TSHR-289 to neutralize TBAb activity in two rare hypothyroid patients with pure TBAb activity lacking agonist activity. IgG from both patients was extremely potent in the TBAb assay. Unlike with TSAb, preincubation of the IgG with a large excess of active TSHR-289 (20 microg/mL) revealed a remarkable divergence. TBAb activity from one patient was totally neutralized whereas in the other patient TBAb activity was totally unaffected. In conclusion, using a new approach, we...Continue Reading

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Citations

Dec 5, 2003·Molecular and Cellular Endocrinology·Nils G MorgenthalerAndreas Bergmann
Jun 14, 2005·Trends in Endocrinology and Metabolism : TEM·Matthias SchottNils G Morgenthaler
Jun 25, 2008·Nature Clinical Practice. Endocrinology & Metabolism·R A Ajjan, A P Weetman
Jan 31, 2004·Thyroid : Official Journal of the American Thyroid Association·Cornelia Lenzner, Nils G Morgenthaler
Mar 9, 2005·Thyroid : Official Journal of the American Thyroid Association·Ileana G S RubioGeraldo Medeiros-Neto
Sep 8, 2007·Thyroid : Official Journal of the American Thyroid Association·Basil Rapoport, Sandra M McLachlan
Oct 11, 2008·Thyroid : Official Journal of the American Thyroid Association·Marian Ludgate, Charles H Emerson
Jul 18, 2002·The Journal of Clinical Investigation·Gregorio D ChazenbalkBasil Rapoport
Aug 23, 2008·Endocrinology·Syed A MorshedTerry F Davies
Jul 26, 2012·Journal of Molecular Endocrinology·Ricardo Núñez MiguelBernard Rees Smith
Jul 3, 2010·Autoimmunity Reviews·Klaus ZöphelMatthias Schott
Jun 24, 2004·Clinical Endocrinology·Sandra M McLachlan, Basil Rapoport
Jan 13, 2018·Frontiers in Immunology·Sandra M McLachlan, Basil Rapoport
Apr 14, 2005·Endocrine Reviews·Sandra M McLachlanBasil Rapoport
Dec 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pavel N PichurinSandra M McLachlan

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