Hypersensitivity: Stimulatory (Type V)

Anthony P Weetman, University of Sheffield, Sheffield, UK

Published online: April 2001

DOI: 10.1038/npg.els.0001435

Type V hypersensitivity is the final type of hypersensitivity in which antibodies are produced with the property of stimulating specific cell targets. The clearest example is Graves disease caused by antibodies that stimulate the thyroid-stimulating hormone receptor, leading to overactivity of the thyroid gland.

Keywords: stimulatory hyper sensitivity; type V hypersensitivity; graves disease; stimulatory antibodies

Figure 1. Graves disease. There is a moderate diffuse goitre, evidence of weight loss due to thyrotoxicosis, and changes of thyroid-associated ophthalmopathy (eyelid retraction, proptosis due to the eyeball being pushed forward by swollen extraocular muscles, and periorbital oedema).
Figure 2. (a) Normal feedback control of thyroid hormone synthesis; (b) situation in Graves disease. T4, thyroxine; T3, triiodothyronine; TSH, thyroid-stimulating hormone.
Figure 3. Regulatory cascades controlled by the thyroid-stimulating hormone (TSH) receptor (TSH-R). TBAb, thyroid-blocking antibodies; TSAb, thyroid-stimulating antibodies; PLC, phospholipase C; IP, inositol phosphate; DAG, diacylglycerol; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate. With permission from Van Sande J, Parma J, Tonacehera M, Swillen S, Dumont J and Vassart G (1995) Somatic and germline mutations of the TSH receptor gene in thyroid disease. Journal of Clinical Endocrinology and Metabolism 80: 2577–2585. ©The Endocrine Society.
close
 References
    Adams DD and Purves HD (1956) Abnormal responses in the assay of thyrotrophin. Proceedings of the University of Otago Medical School 34: 11–12.
    Brix TH, Kyvik KO and Hegedüs L (1998) What is the evidence of genetic factors in the etiology of Graves' disease? A brief review. Thyroid 8: 627–634.
    Costagliola S, Khoo D and Vassart G (1998) Production of bioactive amino-terminal domain of the thyrotropin receptor via insertion in the plasma membrane by a glycosylphosphatidylinositol anchor. FEBS Letters 436: 427–433.
    Da Costa CR and Johnstone AP (1998) Production of the thyrotrophin receptor extracellular domain as a glycosylphosphatidylinositol-anchored membrane protein and its interaction with thyrotrophin and autoantibodies. Journal of Biological Chemistry 273: 11874–11880.
    Davies TF, Roti E, Braverman LE and DeGroot LJ (1998) Thyroid controversy – stimulating antibodies. Journal of Clinical Endocrinology and Metabolism 83: 3777–3781.
    Drexhage HA (1996) Autoimmunity and thyroid growth. Where do we stand? European Journal of Endocrinology 135: 39–45.
    Fiebiger E, Maurer D, Holub H et al. (1995) Serum IgG autoantibodies directed against the chain of FcRI: a selective marker and pathogenetic factor for a distinct subset of chronic urticaria patients? Journal of Clinical Investigation 96: 2602–2612.
    Jaume JC, Kakinuma A, Chazenbalk GD, Rapoport B and McLachlan SM (1997) Thyrotropin receptor autoantibodies in serum are present at much lower levels than thyroid peroxidase autoantibodies: analysis by flow cytometry. Journal of Clinical Endocrinology and Metabolism 82: 500–507.
    book Kendall-Taylor P (1998) "Thyrotoxicosis". In: Grossman A (ed.) Clinical Endocrinology, 2nd edn, pp. 328–358. Oxford: Blackwell Science.
    Nagayama Y, Kaufman KD, Seto P and Rapoport B (1989) Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor. Biochemical and Biophysical Research Communications 165: 1184–1190.
    Parmentier M, Libert F, Maenhaut C et al. (1989) Molecular cloning of the thyrotropin receptor. Science 246: 1620–1622.
    Perret J, Ludgate M, Libert F et al. (1990) Stable expression of the human TSH receptor in CHO cells and characterization of differentially expressing clones. Biochemical and Biophysical Research Communications 171: 1044–1050.
    Perros P and Kendall-Taylor P (1992) Biological activity of autoantibodies from patients with thyroid-associated ophthalmopathy: in vitro effects on porcine extraocular myoblasts. Quarterly Journal of Medicine 84: 691–706.
    Rapoport B, McLachlan SM, Kakinuma A and Chazenbalk GD (1996) Critical relationship between autoantibody recognition and thyrotropin receptor maturation as reflected in the acquisition of complex carbohydrate. Journal of Clinical Endocrinology and Metabolism 81: 2525–2533.
    Rees Smith B, McLachlan SM and Furmaniak J (1988) Autoantibodies to the thyrotropin receptor. Endocrine Reviews 9: 106–121.
    Rotella CM, Zonefrati R, Toccafondi R, Valente WA and Kohn LD (1986) Ability of monoclonal antibodies to the thyrotropin receptor to increase collagen synthesis in human fibroblasts: an assay which appears to measure exophthalmogenic immunoglobulins in Graves' sera. Journal of Clinical Endocrinology and Metabolism 62: 357–367.
    Tahara K, Ishikawa N, Yamamoto K et al. (1997) Epitopes for thyroid stimulating and blocking autoantibodies on the extracellular domain of the human thyrotropin receptor. Thyroid 7: 867–877.
    Taylor SI, Barbetti F, Accili D, Roth J and Gorden P (1989) Syndromes of autoimmunity and hypoglycaemia. Endocrinology and Metabolism Clinics of North America 18: 123–143.
    Van Sande J, Parma J, Tonacehera M, Swillens S, Dumont J and Vassart (1995) Somatic and germline mutations of the TSH receptor gene in thyroid disease. Journal of Clinical Endocrinology and Metabolism 80: 2577–2585.
    Wallukat G, Blasig IE, Morwinski R, Herrmann H-J and Rohde E (1995) The sera of spontaneously hypertensive rats contain agonistic autoantibodies against the 1-adrenoceptor. Journal of Hypertension 13: 1031–1036.
    Watson PF, Ajjan RA, Phipps J, Metcalfe R and Weetman AP (1998) A new chemiluminescent assay for the rapid detection of thyroid stimulating antibodies in Graves' disease. Clinical Endocrinology 49: 577–581.
    Weetman AP and McGregor AM (1994) Autoimmune thyroid disease: further developments in our understanding. Endocrine Reviews 15: 788–830.
    Weetman AP, Yateman ME, Ealey PA et al. (1990) Thyroid-stimulating antibody activity between different immunoglobulin G subclasses. Journal of Clinical Investigation 86: 723–727.
    Weetman AP, Tandon T and Morgan BP (1992) Antithyroid drugs and release of inflammatory mediators by complement-attacked thyroid cells. Lancet 340: 633–636.
    Zakarija M (1983) Immunochemical characterisation of the thyroid-stimulating antibody (TSAb) of Graves' disease: evidence for restricted heterogeneity. Journal of Clinical and Laboratory Immunology 10: 77–85.
 Further Reading
    book Davies TF (ed.) (1998) "Newer aspects of Graves' disease". Baillière's Clinical Endocrinology and Metabolism 11: 431–601.
    Greaves MW (1995) Chronic urticaria. New England Journal of Medicine 332: 1767–1772.
    Heufelder AE (1995) Involvement of the orbital fibroblast and TSH receptor in the pathogenesis of Graves' ophthalmopathy. Thyroid 5: 331–340.
    Ludgate ME and Vassart G (1995) The thyrotropin receptor as a model to illustrate receptor and receptor antibody diseases. Baillière's Clinical Endocrinology and Metabolism 9: 95–113.
    Prabhakar BS, Fan J-L and Seetharamaiah G (1997) Thyrotropin-receptor-mediated diseases: a paradigm for receptor autoimmunity. Immunology Today 18: 437–442.
    Rapoport B, Chazenbalk GD, Jaume JC and McLachlan SM (1998) The thyrotropin (TSH)-releasing hormone receptor: interaction with TSH and autoantibodies. Endocrine Reviews 19: 673–716.

Related Sub-Topics:

Allergy and Hypersensitivity
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Hypersensitivity: Stimulatory (Type V)
 
How to Cite close
Weetman, Anthony P(Apr 2001) Hypersensitivity: Stimulatory (Type V). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001435]