NDLI: Graves' disease TSHR-stimulating antibodies (TSAbs) induce the activation of immature thymocytes: a clue to the riddle of TSAbs generation?

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fernández-Doblas, Joaquín Marín-Sánchez, Ana Gómez-Pau, Ana Abella, Raúl Tonacchera, Massimo Giménez-Barcons, Mireia Obiols, Gabriel Pujol-Borrell, Ricardo Colobran, Roger Casteràs, Anna Lucas-Martín, Ana
Description	Author Affiliation: Giménez-Barcons M ( Vall d'Hebron Institute de Recerca, 08035 Barcelona, Spain); Colobran R ( Vall d'Hebron Institute de Recerca, 08035 Barcelona, Spain); Gómez-Pau A ( Vall d'Hebron Institute de Recerca, 08035 Barcelona, Spain); Marín-Sánchez A ( Servei d'Immunologia, Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain); Casteràs A ( Servei de Endocrinologia, Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain); Obiols G ( Servei de Endocrinologia, Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain); Abella R ( Servei de Cirurgia, Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain); Fernández-Doblas J ( Servei de Cirurgia, Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain); Tonacchera M ( Department of Clinical and Experimental Medicine, Pisa University, 56126 Pisa, Italy); Lucas-Martín A ( Departament de Biologia Cellular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain); Pujol-Borrell R ( Vall d'Hebron Institute de Recerca, 08035 Barcelona, Spain)
Abstract	Graves' disease (GD) is an autoimmune thyroid disease defined by the production of stimulating autoantibodies to the thyroid-stimulating hormone receptor (TSHR) (TSAbs) that induce a sustained state of hyperthyroidism in patients. We previously demonstrated that TSHR, the target of this autoimmune response, is also a key susceptibility gene for GD, probably acting through thymic-dependent central tolerance. We also showed that TSHR is, unexpectedly, expressed in thymocytes. In this report, we confirm the expression of TSHR in thymocytes by protein immunoblotting and quantitative PCR, and show that expression is confined to maturing thymocytes. Using functional assays, we show that thymic TSHR is functional and that TSAbs can stimulate thymocytes through this receptor. This new activity of TSAbs on thymocytes may: 1) explain GD-associated thymic enlargement (hyperplasia), and 2) suggest the provocative hypothesis that the continuous stimulation of thymocytes by TSAbs could lead to a vicious cycle of iterative improvement of the affinity and stimulating capability of initially low-affinity antibacterial (e.g., Yersinia) Abs cross-reactive with TSHR, eventually leading to TSAbs. This may help to fill one of the gaps in our present understanding of unusual characteristics of TSAbs.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	9
Volume Number	194
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Autoantibodies Immunology Graves Disease Lymphocyte Activation Receptors, Thyrotropin Thymocytes Adolescent Child, Preschool Infant Genetics Cytology Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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