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. 2000 Jan;84(1):103–106. doi: 10.1136/bjo.84.1.103

Serum levels of soluble Fas in patients with Graves' ophthalmopathy

K Ohtsuka 1, M Hashimoto 1
PMCID: PMC1723224  PMID: 10611108

Abstract

AIM—To assess levels of soluble Fas (sFas) in the sera of patients with Graves' ophthalmopathy.
METHODS—The subjects in this study were 43 patients with Graves' ophthalmopathy and 11 normal subjects. Serum levels of sFas were determined by sandwich enzyme linked immunosorbent assay. In addition, serum levels of thyroid stimulating antibody (TSAB) were also measured in all the patients.
RESULTS—The mean serum level of sFas was 1.35 (SD 2.03) ng/ml in patients with Graves' ophthalmopathy, and 0.93 (0.32) ng/ml in normal subjects. Serum levels of sFas in the subgroup of 24 patients with diplopia (1.98 (2.56) ng/ml) were significantly higher than those in the subgroup of 19 patients without diplopia (0.56 (0.24) ng/ml) and normal subjects (p <0.001). Serum levels of sFas in the subgroup of 27 patients with extraocular muscle hypertrophy (1.81 (2.46) ng/ml) were significantly higher than those in the subgroup of 16 patients without extraocular muscle hypertrophy (0.58 (0.26) ng/ml) among the patients with Graves' ophthalmopathy and normal subjects (p <0.001). Serum levels of sFas were not significantly different between the subgroup of 24 patients with proptosis (1.15 (0.98) ng/ml) and the subgroup of 19 patients without proptosis (1.61 (2.88)). In contrast, the serum levels of TSAB in the subgroup of patients with proptosis (723% (1161%)) were significantly higher than those in the subgroup of patients without proptosis (194% (122%)) (p <0.05).
CONCLUSIONS—Elevated sFas levels were associated with extraocular muscle disorders but not with proptosis. On the other hand, elevated TSAB levels were associated with proptosis but not with extraocular muscle disorders, suggesting different immunological mechanisms for the extraocular muscle disorders and proptosis in Graves' ophthalmopathy. Determination of the serum levels of sFas and TSAB could provide useful markers for evaluation of the immunological processes involved in the development of Graves' ophthalmopathy.



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Figure 1  .

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Serum levels of sFas in six subgroups of patients with Graves' ophthalmopathy: diplopia negative and positive, extraocular muscle hypertrophy negative and positive, proptosis negative and positive groups, and normal subjects.

Figure 2  .

Figure 2  

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Serum levels of TSAB in six subgroups of patients with Graves' ophthalmopathy: diplopia negative and positive, extraocular muscle hypertrophy negative and positive, and proptosis negative and positive groups.

Figure 3  .

Figure 3  

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Relations between sFas levels and titres of TSAB (A), TGAB (B), and TPOAB (C).

Selected References

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

  1. Bahn R. S., Heufelder A. E. Retroocular fibroblasts: important effector cells in Graves' ophthalmopathy. Thyroid. 1992 Spring;2(1):89–94. doi: 10.1089/thy.1992.2.89. [DOI] [PubMed] [Google Scholar]
  2. Bartley G. B. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc. 1994;92:477–588. [PMC free article] [PubMed] [Google Scholar]
  3. Bijl M., van Lopik T., Limburg P. C., Spronk P. E., Jaegers S. M., Aarden L. A., Smeenk R. J., Kallenberg G. G. Do elevated levels of serum-soluble fas contribute to the persistence of activated lymphocytes in systemic lupus erythematosus? J Autoimmun. 1998 Oct;11(5):457–463. doi: 10.1006/jaut.1998.0233. [DOI] [PubMed] [Google Scholar]
  4. Bolonkin D., Tate R. L., Luber J. H., Kohn L. D., Winand R. J. Experimental exophthalmos. Binding of thyrotropin and an exophthalmogenic factor derived from thyrotropin to retro-orbital tissue plasma membranes. J Biol Chem. 1975 Aug 25;250(16):6516–6521. [PubMed] [Google Scholar]
  5. Cheng J., Zhou T., Liu C., Shapiro J. P., Brauer M. J., Kiefer M. C., Barr P. J., Mountz J. D. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science. 1994 Mar 25;263(5154):1759–1762. doi: 10.1126/science.7510905. [DOI] [PubMed] [Google Scholar]
  6. Drappa J., Vaishnaw A. K., Sullivan K. E., Chu J. L., Elkon K. B. Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity. N Engl J Med. 1996 Nov 28;335(22):1643–1649. doi: 10.1056/NEJM199611283352204. [DOI] [PubMed] [Google Scholar]
  7. Heufelder A. E., Bahn R. S. Detection and localization of cytokine immunoreactivity in retro-ocular connective tissue in Graves' ophthalmopathy. Eur J Clin Invest. 1993 Jan;23(1):10–17. doi: 10.1111/j.1365-2362.1993.tb00712.x. [DOI] [PubMed] [Google Scholar]
  8. Heufelder A. E., Bahn R. S. Modulation of Graves' orbital fibroblast proliferation by cytokines and glucocorticoid receptor agonists. Invest Ophthalmol Vis Sci. 1994 Jan;35(1):120–127. [PubMed] [Google Scholar]
  9. Inoue A., Koh C. S., Sakai T., Yamazaki M., Yanagisawa N., Usuku K., Osame M. Detection of the soluble form of the Fas molecule in patients with multiple sclerosis and human T-lymphotropic virus type I-associated myelopathy. J Neuroimmunol. 1997 May;75(1-2):141–146. doi: 10.1016/s0165-5728(97)00012-x. [DOI] [PubMed] [Google Scholar]
  10. Kazuo K., Fujikado T., Ohmi G., Hosohata J., Tano Y. Value of thyroid stimulating antibody in the diagnosis of thyroid associated ophthalmopathy of euthyroid patients. Br J Ophthalmol. 1997 Dec;81(12):1080–1083. doi: 10.1136/bjo.81.12.1080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ludgate M. E., Vassart G. The thyrotropin receptor as a model to illustrate receptor and receptor antibody diseases. Baillieres Clin Endocrinol Metab. 1995 Jan;9(1):95–113. doi: 10.1016/s0950-351x(95)80851-5. [DOI] [PubMed] [Google Scholar]
  12. Morris J. C., 3rd, Hay I. D., Nelson R. E., Jiang N. S. Clinical utility of thyrotropin-receptor antibody assays: comparison of radioreceptor and bioassay methods. Mayo Clin Proc. 1988 Jul;63(7):707–717. doi: 10.1016/s0025-6196(12)65533-5. [DOI] [PubMed] [Google Scholar]
  13. Nozawa K., Kayagaki N., Tokano Y., Yagita H., Okumura K., Hasimoto H. Soluble Fas (APO-1, CD95) and soluble Fas ligand in rheumatic diseases. Arthritis Rheum. 1997 Jun;40(6):1126–1129. doi: 10.1002/art.1780400617. [DOI] [PubMed] [Google Scholar]
  14. Rotella C. M., Zonefrati R., Toccafondi R., Valente W. A., Kohn L. D. 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. J Clin Endocrinol Metab. 1986 Feb;62(2):357–367. doi: 10.1210/jcem-62-2-357. [DOI] [PubMed] [Google Scholar]
  15. Shimaoka Y., Hidaka Y., Okumura M., Takeoka K., Tada H., Amino N. Serum concentration of soluble Fas in patients with autoimmune thyroid diseases. Thyroid. 1998 Jan;8(1):43–47. doi: 10.1089/thy.1998.8.43. [DOI] [PubMed] [Google Scholar]
  16. Tallstedt L., Norberg R. Immunohistochemical staining of normal and Graves' extraocular muscle. Invest Ophthalmol Vis Sci. 1988 Feb;29(2):175–184. [PubMed] [Google Scholar]
  17. Weetman A. P., Cohen S., Gatter K. C., Fells P., Shine B. Immunohistochemical analysis of the retrobulbar tissues in Graves' ophthalmopathy. Clin Exp Immunol. 1989 Feb;75(2):222–227. [PMC free article] [PubMed] [Google Scholar]

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