Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1994 Apr;81(4):643–647.

Expression and function of multiple regulators of complement activation in autoimmune thyroid disease.

N Tandon 1, S L Yan 1, B P Morgan 1, A P Weetman 1
PMCID: PMC1422378  PMID: 7518800

Abstract

Membrane attack complexes of complement occur around thyroid follicles in Graves' disease and Hashimoto's thyroiditis. The lytic potential of such complexes is controlled by membrane-bound and fluid phase regulators and we have investigated the role of these in autoimmune thyroid disease. By immunohistochemical staining, clusterin and S-protein were found in all nine thyroid specimens from patients with Graves' disease and S-protein was found in one of two Hashimoto glands. CD46, CD55 and CD59 were found on thyroid cells in all specimens. CD46 and CD55 expression occurred on thyroid cells cultured in vitro and was increased significantly by culture with interleukin-1 (IL-1) and interferon-gamma (IFN-gamma), which are known to be released by the lymphocytic infiltrate in these conditions. Blocking CD55 had a weak and inconsistent effect on complement-mediated thyroid cell killing in vitro but, in four of five experiments, blocking CD46 enhanced killing. However, the effect of blocking CD59 was greater in all cases than blocking CD46 or CD55. Expression of these fluid phase and membrane-bound proteins may be important in determining the severity of thyroid damage produced by complement fixation in Graves' disease and Hashimoto's thyroiditis.

Full text

PDF

Images in this article

645Figure 1
on p.645

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Choi N. H., Nakano Y., Tobe T., Mazda T., Tomita M. Incorporation of SP-40,40 into the soluble membrane attack complex (SMAC, SC5b-9) of complement. Int Immunol. 1990;2(5):413–417. doi: 10.1093/intimm/2.5.413. [DOI] [PubMed] [Google Scholar]
  2. Dahlbäck K., Löfberg H., Dahlbäck B. Immunohistochemical demonstration of vitronectin in association with elastin and amyloid deposits in human kidney. Histochemistry. 1987;87(6):511–515. doi: 10.1007/BF00492465. [DOI] [PubMed] [Google Scholar]
  3. French L. E., Tschopp J., Schifferli J. A. Clusterin in renal tissue: preferential localization with the terminal complement complex and immunoglobulin deposits in glomeruli. Clin Exp Immunol. 1992 Jun;88(3):389–393. doi: 10.1111/j.1365-2249.1992.tb06459.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Inoue K., Niesen N., Biesecker G., Milgrom F., Albini B. Role of late complement components in experimental autoimmune thyroiditis. Clin Immunol Immunopathol. 1993 Jan;66(1):1–10. doi: 10.1006/clin.1993.1001. [DOI] [PubMed] [Google Scholar]
  5. Inoue K., Niesen N., Milgrom F., Albini B. Transfer of experimental autoimmune thyroiditis by in situ perfusion of thyroids with immune sera. Clin Immunol Immunopathol. 1993 Jan;66(1):11–17. doi: 10.1006/clin.1993.1002. [DOI] [PubMed] [Google Scholar]
  6. Jenne D. E., Tschopp J. Molecular structure and functional characterization of a human complement cytolysis inhibitor found in blood and seminal plasma: identity to sulfated glycoprotein 2, a constituent of rat testis fluid. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7123–7127. doi: 10.1073/pnas.86.18.7123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jenne D., Stanley K. K. Molecular cloning of S-protein, a link between complement, coagulation and cell-substrate adhesion. EMBO J. 1985 Dec 1;4(12):3153–3157. doi: 10.1002/j.1460-2075.1985.tb04058.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Johnstone R. W., Loveland B. E., McKenzie I. F. Identification and quantification of complement regulator CD46 on normal human tissues. Immunology. 1993 Jul;79(3):341–347. [PMC free article] [PubMed] [Google Scholar]
  9. Kalderon A. E., Bogaars H. A. Immune complex deposits in Graves' disease and Hashimoto's thyroiditis. Am J Med. 1977 Nov;63(5):729–734. doi: 10.1016/0002-9343(77)90159-0. [DOI] [PubMed] [Google Scholar]
  10. Kirszbaum L., Sharpe J. A., Murphy B., d'Apice A. J., Classon B., Hudson P., Walker I. D. Molecular cloning and characterization of the novel, human complement-associated protein, SP-40,40: a link between the complement and reproductive systems. EMBO J. 1989 Mar;8(3):711–718. doi: 10.1002/j.1460-2075.1989.tb03430.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lisanti M. P., Sargiacomo M., Graeve L., Saltiel A. R., Rodriguez-Boulan E. Polarized apical distribution of glycosyl-phosphatidylinositol-anchored proteins in a renal epithelial cell line. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9557–9561. doi: 10.1073/pnas.85.24.9557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Liszewski M. K., Post T. W., Atkinson J. P. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol. 1991;9:431–455. doi: 10.1146/annurev.iy.09.040191.002243. [DOI] [PubMed] [Google Scholar]
  13. Lublin D. M., Atkinson J. P. Decay-accelerating factor: biochemistry, molecular biology, and function. Annu Rev Immunol. 1989;7:35–58. doi: 10.1146/annurev.iy.07.040189.000343. [DOI] [PubMed] [Google Scholar]
  14. Medof M. E., Walter E. I., Rutgers J. L., Knowles D. M., Nussenzweig V. Identification of the complement decay-accelerating factor (DAF) on epithelium and glandular cells and in body fluids. J Exp Med. 1987 Mar 1;165(3):848–864. doi: 10.1084/jem.165.3.848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Murphy B. F., Kirszbaum L., Walker I. D., d'Apice A. J. SP-40,40, a newly identified normal human serum protein found in the SC5b-9 complex of complement and in the immune deposits in glomerulonephritis. J Clin Invest. 1988 Jun;81(6):1858–1864. doi: 10.1172/JCI113531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Tandon N., Morgan B. P., Weetman A. P. Expression and function of membrane attack complex inhibitory proteins on thyroid follicular cells. Immunology. 1992 Feb;75(2):372–377. [PMC free article] [PubMed] [Google Scholar]
  17. Weetman A. P., Cohen S. B., Oleesky D. A., Morgan B. P. Terminal complement complexes and C1/C1 inhibitor complexes in autoimmune thyroid disease. Clin Exp Immunol. 1989 Jul;77(1):25–30. [PMC free article] [PubMed] [Google Scholar]
  18. Weetman A. P., Freeman M., Morgan B. P. Thyroid follicular cell function after non-lethal complement membrane attack. Clin Exp Immunol. 1990 Oct;82(1):69–74. doi: 10.1111/j.1365-2249.1990.tb05405.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Weetman A. P., Tandon N., Morgan B. P. Antithyroid drugs and release of inflammatory mediators by complement-attacked thyroid cells. Lancet. 1992 Sep 12;340(8820):633–636. doi: 10.1016/0140-6736(92)92171-b. [DOI] [PubMed] [Google Scholar]
  20. Weetman A. P., Volkman D. J., Burman K. D., Gerrard T. L., Fauci A. S. The in vitro regulation of human thyrocyte HLA-DR antigen expression. J Clin Endocrinol Metab. 1985 Nov;61(5):817–824. doi: 10.1210/jcem-61-5-817. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES