Association of HLA Class I and Class II Genes and Adrenal Steroid 21-Hydroxylase Gene with Subacute (de Quervain’s) and Hashimoto’s Thyroiditis: Evidence for an Altered Negative Feedback in Hashimoto’s Thyroiditis

  • B. O. Boehm
  • E. Schifferdecker
  • B. Manfras
  • P. Kühnl
  • G. Holzberger
  • C. Rosak
  • K. Schöffling


It is a striking feature of organ-specific autoimmune diseases that they are linked to alleles of class I and class II genes of the MHC gene region [1]; however, until recently the nature of this association was unclear. The hypothesis was then put forward that the MHC molecules per se play a major role in the immune response. They act as restriction elements when antigen-presenting cell and T cell meet in immune recognition either in a physiological milieu or in an autoimmune state [2]. Direct evidence for this hypothesis was deduced from inappropriate expression of MHC molecules on target tissues of an autoimmune attack, i.e., class II expression on pancreatic beta cells in recent-onset type I diabetes mellitus or class I and class II overexpression on thyroid epithelial cells in Graves’ disease [3]. Presentation of an antigen or an autoantigen is a prerequisite in organ-specific autoimmunity, but also specific recognition by the T-cell receptor supplemented by helper factors is necessary for an immune response [2]. Since organ-specific autoimmune diseases are chronic diseases, it might he speculated that the helper factors (interleukins), which provide a positive feedback, play an important role in the maintenance of chronic inflammation during target organ destruction. Also, negative feedback mechanisms such as T-suppressor circuits may be impaired [4].


Congenital Adrenal Hyperplasia Adrenal Steroid ACTH Stimulation Test Subacute Thyroiditis Histocompatibility Leukocyte Antigen 
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  1. 1.
    Tiwari JL, Terasaki PI (1985) HLA and disease associations. Springer, New YorkCrossRefGoogle Scholar
  2. 2.
    Strominger JL (1986) Biology of the human histocompatibility leukocyte antigen (HLA) system and a hypothesis regarding the generation of autoimmune diseases. J Clin Invest 77:1411PubMedCrossRefGoogle Scholar
  3. 3.
    Hanafusa T, Pujol-Borrell R, Chiovato L, Russell RCG, Doniach D, Bottazzo GF (1983) Aberrant expression of HLA-DR expression on thyrocytes in Graves’ disease: relevance to autoimmunity. Lancet 2:1111PubMedCrossRefGoogle Scholar
  4. 4.
    Schwartz RH (1989) Acquisition of immunologic self-tolerance. Cell 57:1073PubMedCrossRefGoogle Scholar
  5. 5.
    White PC, New MI, Dupont B (1985) Adrenal 21-hydroxylase cytochrome P-450 genes within the MHC class III region. Immunol Rev 87:123PubMedCrossRefGoogle Scholar
  6. 6.
    Terasaki PI, McClelland M (1964) Microdroplet assay of human serum cytotoxins. Nature 204:998PubMedCrossRefGoogle Scholar
  7. 7.
    Van Rood JJ, Van Leeuwen A, Ploem JS (1976) Simultaneous detection of two cell populations by two colour fluorescence and application to the recognition of B-cell determinants. Nature 262:795PubMedCrossRefGoogle Scholar
  8. 8.
    Roitt IM, Campbell PN, Doniach D (1958) The nature of the thyroid autoantibodies present in patients with Hashimoto’s thyroiditis (lymphadenoid goitre). Biochem J 69:248PubMedGoogle Scholar
  9. 9.
    Misakia T, Konishi J, Nakashima T, Ilda Y, Kasagi K, Endo K, Uchiyama T, Kuma K, Torizuka K (1985) Immunohistological phenotyping of thyroid infiltrating lymphocytes in Graves’ disease and Hashimoto’s thyroiditis. Clin Exp Immunol 60:104Google Scholar
  10. 10.
    Wraith DC, McDevitt HO, Steinmann L, Acha-Orbea H (1989) T cell recognition as the target for immune intervention in autoimmune disease. Cell 57:709PubMedCrossRefGoogle Scholar
  11. 11.
    Albert ED, Baur MP, Mayr WR (1984) Histocompatibility testing 1984. Springer, Berlin Heidelberg New YorkGoogle Scholar
  12. 12.
    Farid NR, Hawe BS, Walfish PG (1983) Increased frequency of HLA-DR3 and 5 in the syndromes of painless thyroiditis with transient thyroiditis: evidence of an autoimmune etiology. Clin Endocrinol 19:699CrossRefGoogle Scholar
  13. 13.
    Boehm BO, Rosak C, Boehm TLJ, Kuehnl P, White PC, Schöffling K (1986) Classical and late-onset forms of congenital adrenal hyperplasia caused by 21-OH deficiency reveal different alterations in the C4/21-OH gene region. Mol. Biol Med 3:437Google Scholar
  14. 14.
    New MI, Dupont B, Pang S, Pollack M, Levine LS (1981) An update of congenital adrenal hyperplasia. Recent Progr Horm Res 37:105PubMedGoogle Scholar
  15. 15.
    Fässler R, Schaunstein K, Krömer G, Schwartz S, Wick G (1986) Elevation of corticoste-roid-binding globulin in Obese strain (OS) chickens: possible implications for the disturbed immunoregulation and the developement of spantaneous thyroiditis. J Immunol 136:3657PubMedGoogle Scholar
  16. 16.
    Gause WC, Marsh JA (1985) Effects of testosterone on the development of autoimmune thyroiditis in two strains of chicken. Clin Immunol Immunopathol 36:10PubMedCrossRefGoogle Scholar
  17. 17.
    Warren RS, Donner DB, Starner HF, Brennan MF (1987) Modulation of endogenous hormone action by recombinant human tumor necrosis factor. Proc Natl Acad Sci USA 84:8619PubMedCrossRefGoogle Scholar
  18. 18.
    Zuckermann SH, Shellhaas J, Butler LD (1989) Differential regulation of lipopolysac-charide-induced interleukin 1 and tumor necrosis factor synthesis: effects of endogenous and exogenous glucocorticoids and the role of the pituitary-adrenal axis. Eur J Immunol 19:301CrossRefGoogle Scholar
  19. 19.
    Weber PJ, Pert A (1989) The periaqueductal gray matter mediates opiate-induced immunosuppression. Science 245:188PubMedCrossRefGoogle Scholar
  20. 20.
    Davis JE, Rich RR, Van M, Le HV, Pollack MS, Cook RG (1987) Defective antigen presentation and novel structural properties of DR1 from an HLA haplotype associated with 21-hydroxylase deficiency. J Clin Invest 80:998PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • B. O. Boehm
  • E. Schifferdecker
  • B. Manfras
  • P. Kühnl
  • G. Holzberger
  • C. Rosak
  • K. Schöffling

There are no affiliations available

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