Heterogeneity of TSH Receptor-directed Antibodies (TRAb) and Their Significance

  • Margita Zakarija


In reviewing TRAb in Graves’ disease there is no longer need for debate about the role of TSAb itself. This antibody is generally accepted as causing hyperthyroidism through binding to a component of the TSH receptor and stimulation of adenylate cyclase. Formerly we used an assay based upon measurement of an increase in cAMP in human thyroid slices and found TSAb in over 90% of 102 patients (1). Now the procedure developed by Kasagi et al (2) and refined by Rapoport and his colleagues (3) has replaced the slice assay. This technique entails incubation of human thyroid cells in primary monolayer culture with patients’ IgG in hypotonic medium and subsequent measurement of cAMP that has been released into the medium. With this assay we find 100% positive results with IgG from Graves’ disease patients. This high sensitivity apparently is not associated with decreased specificity as judged by negative results with IgG from over 90 patients with thyroid disorders of nonautoimmune origin. A current alternate and more convenient procedure is the similar use of functioning rat thyroid (FRTL-5) cells in continuous culture (4), but not all IgG positive in the human thyroid cell assay give- a response in this system.


Endemic Goiter Hypotonic Medium Primary Monolayer Culture Neonatal Hypothyroidism Human Thyroid Cell 
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  1. 1.
    Zakarija M, McKenzie JM, Banovac K 1980. Ann Intern Med 93:28PubMedGoogle Scholar
  2. 2.
    Kasagi K, Konishi J, Iida Y, Ikekubo K, Mori T, Kuma K, Torizuka K 1982 J Clin Endocrinol Metab 54:108PubMedCrossRefGoogle Scholar
  3. 3.
    Rapoport B, Greenspan FS, Filleti S, Pepitone M 1984 J Clin Endocrinol Metab 58:332PubMedCrossRefGoogle Scholar
  4. 4.
    Vitti P, Rotella CM, Valente WA, Cohen J, Aloj SM, Laccetti P, Ambesi-Impiombato FS, Grollman EF, Pinchera A, Toccafondi R, Kohn LD 1983 J Clin Endocrinol Metab 57:782PubMedCrossRefGoogle Scholar
  5. 5.
    Kahn CR, Kasuga M, King GL, Grunfeld C 1982 In: Evered D, Whelan J (eds) Receptors, antibodies and disease. Ciba Foundation Symposium 90, Pitman, London, p 91Google Scholar
  6. 6.
    Drachman DB, Angus CV, Adams RN, Michelson JD, Hoffman GJ 1978 N Engl J Med 298:1116PubMedCrossRefGoogle Scholar
  7. 7.
    Smith BR 1976 Immunol Commun 5:345PubMedGoogle Scholar
  8. 8.
    Zakarija M, Garcia A, McKenzie JM 1985 J Clin Invest 76:1885PubMedCrossRefGoogle Scholar
  9. 9.
    Knight J, Laing P, Knight A, Adams D, Ling N 1986 J Clin Endocrinol Metab 62:342PubMedCrossRefGoogle Scholar
  10. 10.
    Zakarija M 1983 J Clin Lab Immunol 10:77PubMedGoogle Scholar
  11. 11.
    Weetman AP, McGregor AM 1984 Endocrine Rev 5:309CrossRefGoogle Scholar
  12. 12.
    Matsuura N, Yamada Y, Nohara Y, Konishi J, Kasagi K, Endo K, Kojima K, Wataya K 1980 N Engl J Med 303:738PubMedCrossRefGoogle Scholar
  13. 13.
    Zakarija M, McKenzie JM, Munro DS 1983 J Clin Invest 72:1352PubMedCrossRefGoogle Scholar
  14. 14.
    Zakarija M, McKenzie JM 1986 J Clin Endocrinol Metab 62:368PubMedCrossRefGoogle Scholar
  15. 15.
    Kohn LD, Alvarez F, Marcocci C, Kohn AD, Corda D, Hoffman WE, Tombaccini D, Valente WA, de Luca M, Santisteban P, Grollman EF 1986 Ann NY Acad Sci 475:157PubMedCrossRefGoogle Scholar
  16. 16.
    McKenzie JM, Zakarija M 1986 In: Ingbar SH, Braverman LE (eds) Werner’s The Thyroid. Lippincott Co., Philadelphia, p 559Google Scholar
  17. 17.
    Konishi J, Iida Y, Kasagi K, Misaki T, Nakashima T, Endo K, Mori T, Shinto S, Nohara Y, Matsuura N, Torizuka K 1985 Ann Intern Med 103:26PubMedGoogle Scholar
  18. 18.
    Iseki M, Shimizu M, Oikawa T, Hojo H, Arikawa K, Ichikawa Y, Momotani N, Ito K 1983 J Clin Endocrinol Metab 57:384PubMedCrossRefGoogle Scholar
  19. 19.
    Koizumi Y, Zakarija M, McKenzie JM In: Gaitan E, Medeiros-Neto G (eds) Frontiers in Thyroidology. Plenum Press, New York, in pressGoogle Scholar
  20. 20.
    Valente WA, Vitti P, Rotella CM, Vaughan MM, Aloj SM, Grollman EF, Ambesi-Impiombato FS, Kohn LD 1983 N Engl J Med 309:1028PubMedCrossRefGoogle Scholar
  21. 21.
    Valente WA, Vitti P, Kohn LD, Brandi ML, Rotella CM, Toccafondi R, Tramontano D, Aloj SM, Ambesi-Impiombato FS 1983 Endocrinol 112:71CrossRefGoogle Scholar
  22. 22.
    Drexhage HA, Bottazzo GF, Doniach D, Bitensky L, Chayen J 1980 Lancet 2: 287CrossRefGoogle Scholar
  23. 23.
    Drexhage HA, Bottazzo GF, Doniach D 1983 In: Chayen J, Bitensky L (eds) Cytochemical Bioassays. Marcel Dekker, New York, p 153Google Scholar
  24. 24.
    Mitchison JM 1971 The Biology of the Cell Cycle. Cambridge University Press, Cambridge, p 58Google Scholar
  25. 25.
    Roger PP, Dumont JE 1982 FEBS Lett 144:209PubMedCrossRefGoogle Scholar
  26. 26.
    Kohn DL, Valente WA, Alvarez FV, Rotella CM, Marcocci C, Toccafondi R, Grollman EF 1985 In: Walfish PG, Wall JR, Volpe R (eds) Autoimmunity and the Thyroid. Academic Press, New York, p 217Google Scholar
  27. 27.
    Medeiros-Neto GA, Halpern A, Cozzi ZS, Lima N, Kohn LD 1986 J Clin Endocrinol Metab 63:644PubMedCrossRefGoogle Scholar
  28. 28.
    Jin S, Hornicek FJ, Neylan D, Zakarija M, McKenzie JM 1986 Endocrinol 119:802CrossRefGoogle Scholar
  29. 29.
    Dere WH, Rapoport B 1986 Molec Cell Endocrinol 44:195PubMedCrossRefGoogle Scholar
  30. 30.
    Ealey PA, Emmerson JM, Bidey SP, Marshall NJ 1985 J Endocrinol 106:203PubMedCrossRefGoogle Scholar
  31. 31.
    Tramontano D, Chin WW, Moses AC, Ingbar SH 1986 J Biol Chem 261:3919PubMedGoogle Scholar
  32. 32.
    Zakarija M, Jin S, McKenzie JM 1986 61st Annual Meeting of the American Thyroid Association, Phoenix, AZ, 1986, p T-17 (Abstract)Google Scholar
  33. 33.
    Tramontano D 1986 68th Annual Meeting of the Endocrine Society, Anaheim, CA, 1986, p 33 (Abstract)Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Margita Zakarija
    • 1
  1. 1.Department of MedicineUniversity of Miami School of MedicineMiamiUSA

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