Bioassays for TSH-receptor autoantibodies: an update.
Immunoglobulins in patients with Graves' disease (GD) that modulate the thyroid stimulating hormone receptor (TSH-R) do so via stimulating cAMP dependent signals (TSI), blocking TSH or inhibition of TSH-receptor activation (TBI) or inducing apoptotic signals. These functional immunoglobulins represent powerful biomarkers of anti-self reactivity in the thyroid and systemic tissues that harbor TSH-R expressing target cells. TSI on thyrocytes induce hyperthyroidism, and TSI on TSH-R fibroblasts of orbital muscles, skin and heart provoke the release of cytokines and antigen-specific T-cell responses leading to systemic inflammation. Bioassays of anti-TSH-R autoantibodies provide decisive information on GD activity. This review examines the past and present bioassays in GD. The critical goal of cell-based anti-TSH-R autoantibody bioassays, to identify the pathogenic immunoglobulins in GD under robust and standardized conditions suitable for routine clinical laboratory practice, is discussed.
Lytton
Simon D
SD
Thyroid Research Laboratory, Department of Medicine I, Gutenberg University Medical Center, Mainz 55101, Germany. simon.lytton@t-online.de
Kahaly
George J
GJ
D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001681:Biological Assay / Q000379:methods; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006111:Graves Disease / Q000276:immunology / Q000503:physiopathology*; D006168:Guinea Pigs; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood; D051379:Mice; D051381:Rats; D011989:Receptors, Thyrotropin / Q000276:immunology*
D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin