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Pathogenesis of Graves’ ophthalmopathy

  • Chapter
Recent Developments in Graves’ Ophthalmopathy

Abstract

Graves’ ophthalmopathy (GO) is a medically incurable, chronic autoimmune process that affects the orbital tissues and is tightly linked with autoimmune thyroid diseases, most notably Graves’ disease (GD). The close clinical association between immunogenic hyperthyroidism, ophthalmopathy, and pretibial dermopathy suggests that the antigen responsible for these diverse conditions is common to thyroid gland, orbital tissues and pretibial skin.1,2 Gross examination of orbital tissues in patients with severe, active GO reveals edematous, enlarged extraocular muscle bodies in conjunction with an increased volume of orbital connective and fatty tissue (Chapter 1). Microscopically, two characteristic abnormalities are apparent: the presence of excessive amounts of hydrophilic glycosaminoglycans (GAGs), predominantly hyaluronic acid and chondroitin sulfate, and marked infiltration of the orbital connective tissue and extraocular muscles by immunocompetent cells (macrophages and T lymphocytes, few B cells). The orbital inflammatory process is likely to be driven by T-cells which, in response to an uncertain antigen, access and infiltrate the orbital space via certain adhesion molecules.1,3 Once recruited, these T cells release numerous cytokines capable of stimulating cell proliferation, GAG synthesis, and generation of new fat cells from orbital adipose precursor cells responding to adipogenic stimuli. Moreover, many of these autocrine and paracrine factors act to alter the expression of an array of immunomodulatory molecules in orbital preadipocyte fibroblasts.

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References

  1. Burch HB, Wartofsky L. Graves’ ophthalmopathy: Current concepts regarding pathogenesis and management. Endocr Rev 1993; 14:747–793.

    PubMed  CAS  Google Scholar 

  2. Bahn RS, Heufelder AE. Mechanisms of disease: Pathogenesis of Graves’ ophthalmopathy. New Engl J Med 1993; 329:1468–1475.

    Article  PubMed  CAS  Google Scholar 

  3. Heufelder AE. Retro-orbital autoimmunity. Bailliere’s Clin Endocrinol Metab 1997; 11: 499–520.

    Article  CAS  Google Scholar 

  4. Werner SC, Coleman DJ, Franzen LA. Ultrasonographic evidence of a consistent orbital involvement in GD. New Engl J Med 1974; 308:420–4.

    Google Scholar 

  5. Amino N, Yuasa T, Yabu Y, Miyai K. Exophthalmos in autoimmune thyroid disease. J Clin Endocrinol Metab 1980; 51:1232–4.

    Article  PubMed  CAS  Google Scholar 

  6. Mauri L, Meienberg O, Roth E, Konig MP. Evaluation of endocrine ophthalmopathy with saccadic eye movements. J Neurol 1984; 231:182–7.

    Article  PubMed  CAS  Google Scholar 

  7. Villadolid MC, Yokoyama N, Izumi M. et al. Untreated Graves’ disease patients without clinical ophthalmopathy demonstrate a high frequency of extraocular muscle (EOM) enlargement by magnetic resonance. J Clin Endocrinol Metab. 1995; 80:2830–3.

    Article  PubMed  CAS  Google Scholar 

  8. Hagg E, Asplund K. Is endocrine ophthalmopathy related to smoking? Brit Med J 1987; 295:634–5.

    Article  CAS  Google Scholar 

  9. Bartalena L, Martino C, Marcocci C. et al. More on smoking habits and Graves’ ophthalmopathy. J Endocrinol Invest 1989; 12:733–7.

    PubMed  CAS  Google Scholar 

  10. Shine B, Fells P, Edwards OM, Weetman AP. Association between Graves’ ophthalmopathy and smoking. Lancet 1990; 335:1261–3.

    Article  PubMed  CAS  Google Scholar 

  11. Tallstedt L, Lundell G, Taube A. Graves’ ophthalmopathy and tobacco smoking. Acta Endocrinol 1993; 129:147–50.

    PubMed  CAS  Google Scholar 

  12. Prummel MF, Wiersinga WM. Smoking and risk of Graves’ disease. JAMA 1993; 269:479–82.

    Article  PubMed  CAS  Google Scholar 

  13. Tellez M, Cooper J, Edmonds C. Graves’ ophthalmopathy in relation to cigarette smoking and ethnic origin. Clin Endocrinol 1992; 36:291–4.

    Article  CAS  Google Scholar 

  14. Metcalfe RA, Weetman AP. Stimulation of extraocular muscle fibroblasts by cytokines and hypoxia: possible role in thyroid-associated ophthalmopathy. Clin Endocrinol 1994; 40:67–72.

    Article  CAS  Google Scholar 

  15. Hofbauer LC, Mühlberg T, König A, Heufelder G, Schworm H-D, Heufelder AE. Soluble interleukin-1 receptor antagonist serum levels in smokers and nonsmokers with Graves’ ophthalmopathy undergoing orbital radiotherapy. J Clin Endocrinol Metab 1997; 82:2244–7.

    Article  PubMed  CAS  Google Scholar 

  16. Weetman AP, Wiersinga WM. Current management of thyroid-associated ophthalmopathy in Europe. Results of an international survey. Clin Endocrinol 1998; 49:21–8.

    Article  CAS  Google Scholar 

  17. Bartalena L, Marcocci C, Bogazzi F. et al. Relation between therapy for hyperthyroidism and the course of Graves’ ophthalmopathy. New Engl J Med 1998; 338:73–8.

    Article  PubMed  CAS  Google Scholar 

  18. Prummel MF, Wiersinga WM, Mourits M Ph, Koornneef L, Berghout A, van der Gaag R. Effect of abnormal thyroid function on the severity of Graves’ ophthalmopathy. Arch Intern Med 1990; 150:1098–1101.

    Article  PubMed  CAS  Google Scholar 

  19. Teng WP, Stark R, Munro AJ, McHardy-Young S, Borysiewicz LK, Weetman AP. Peripheral blood T cell activation after radioiodine treatment for GD. Acta Endocrinol 1990; 122:233–40.

    PubMed  CAS  Google Scholar 

  20. Byrne AP, Delaney WJ. Regression of thyrotoxic ophthalmopathy following lithium withdrawal. Can J Psychiatry 1993; 38:635–7.

    PubMed  CAS  Google Scholar 

  21. Schleusener H, Schernthaner G, Mayr WR. et al. HLA-DR3 and HLA-DR5 associated thyrotoxicosis — two different types of toxic diffuse goiter. J Clin Endocrinol Metab 1983; 56:781–5.

    Article  PubMed  CAS  Google Scholar 

  22. Frecker M, Stenszky V, Balazs C, Kozma L, Kraszits E, Farid NR. Genetic factors in Graves’ ophthalmopathy. Clin Endocrinol 1986; 25:479–85.

    Article  CAS  Google Scholar 

  23. Bech K, Lumholz B, Nerup J. et al. HLA antigens in GD. Acta Endocrinol 1977; 86:510–15.

    PubMed  CAS  Google Scholar 

  24. Allannic H, Fauchet R, Lorcy Y, Gueguen M, LeGuerrier A-M, Genetet B. A prospective study of the relationship between relapse of hyperthyroid GD after antithyroid drugs and HLA haplotype. J Clin Endocrinol Metab 1994; 57:719–22.

    Article  Google Scholar 

  25. Kendall-Taylor P, Stephenson A, Stratton A, Papiha SS, Perros P, Roberts DF. Differentiation of autoimmune ophthalmopathy from Graves’ hyperthyroidism by analysis of genetic markers. Clin Endocrinol 1988; 28:601–10.

    CAS  Google Scholar 

  26. Weetman AP, So AK, Warner CA, Foroni L, Fells P, Shine B. Immunogenetics of Graves’ ophthalmopathy. Clin Endocrinol 1988; 28:619–28.

    CAS  Google Scholar 

  27. Weetman AP, Zhang L, Webb S, Shine B. Analysis of HLA-DQB and HLA-DPB alleles in GD by oligonucleotide probing of enzymatically amplified DNA. Clin Endocrinol 1990; 33:65–71.

    Article  CAS  Google Scholar 

  28. Inoue D, Sato K, Enomoto T. et al. Correlation of HLA types and clinical findings in Japanese patients with hyperthyroid Graves’ disease: evidence indicating the existence of four subpopulations. Clin Endocrinol 1992; 36:75–82.

    Article  CAS  Google Scholar 

  29. Yanagawa T, Hidaka Y, Guimaraes V, Soliman M, DeGroot LJ. CTLA-4 gene polymorphism associated with Graves’ disease in Caucasian population. J Clin Endocrinol Metab 1995; 80:41–5.

    Article  PubMed  CAS  Google Scholar 

  30. Kotsa K, Watson PF, Weetman AP. A CTLA-4 gene polymorphism is associated with both Graves’ disease and autoimmune hypothyroidism. Clin Endocrinol 1997; 46:551–4.

    Article  CAS  Google Scholar 

  31. Brix TH, Christensen K, Holm NV, Harvald B, Hegedüs L. A population-based study of Graves’ disease in Danish twins. Clin Endocrinol 1998; 40:397–400.

    Article  Google Scholar 

  32. Tomer Y, Barbesino G, Keddache M, Greenberg DA, Davies TF. Mapping of a major susceptibility locus for Graves’ disease (GD-1) to chromosome 14q31. J Clin Endocrinol Metab 1997; 82:1645–8.

    Article  PubMed  CAS  Google Scholar 

  33. Barbesino G, Tomer Y, Concepcion ES, Davies TF, Greenberg DA. Linkage analysis of candidate genes in autoimmune thyroid disease. II. Selected gender-related genes and the X-chromosome. J Clin Endocrinol Metab 1998; 83:3290–5.

    Article  PubMed  CAS  Google Scholar 

  34. Kendler DL, Lippa J, Rootman J. The initial clinical characteristics of Graves’ orbitopathy vary with age and sex. Arch Ophthalmol 1993; 111:197–201.

    Article  PubMed  CAS  Google Scholar 

  35. Perros P, Crombie AL, Matthews JNS, Kendall-Taylor P. Age and gender influences the severity of thyroid-associated ophthalmopathy: a study of 101 patients attending a combined thyroid-eye clinic. Clin Endocrinol 1993; 38:367–72.

    Article  CAS  Google Scholar 

  36. Bartels ED. Heredity in Graves’ disease. With remarks on heredity in toxic adenoma in the thyroid, non-toxic goitre, and myxoedema. Copenhagen: Einar Munksgaard, 1943: 3–384.

    Google Scholar 

  37. Howel-Evans AW, Woodrow JC, McDougall CDM, Chew AR, Evans RW. Antibodies in the families of thyrotoxic patients. Lancet 1967; 1:636–641.

    Article  Google Scholar 

  38. Stenszky V, Kozma L, Balazs C, Rochlitz S, Bear JC, Farid NR. The genetics of Graves’ disease: HLA and disease susceptibility. J Clin Endocrinol Metab 1985; 61:735–40.

    Article  PubMed  CAS  Google Scholar 

  39. Heufelder AE, Bahn RS. 1993 Detection and localization of cytokine immunoreactivity in retroocular connective tissue in Graves’ ophthalmopathy. Eur J Clin Invest 23: 10–17.

    Article  PubMed  CAS  Google Scholar 

  40. Heufelder AE, Bahn RS. Elevated expression in situ of selectin and immunoglobulin superfamily adhesion molecules in retroocular connective tissues from patients with Graves’ ophthalmopathy. Clin Exp Immunol 1993; 91: 381–389.

    Article  PubMed  CAS  Google Scholar 

  41. Heufelder AE, Herterich S, Ernst G. et al. Analysis of retroorbital T cell antigen receptor variable region gene usage in patients with Graves’ ophthalmopathy. Eur J Endocrinol 1995; 132:266–277.

    Article  PubMed  CAS  Google Scholar 

  42. Heufelder AE, Wenzel BE, Scriba PC. Antigen receptor variable region repertoires expressed by T cells infiltrating thyroid, retroorbital and pretibial tissue in Graves’ disease. J Clin Endocrinol Metab 1996; 81: 3733–3739.

    Article  PubMed  CAS  Google Scholar 

  43. Bahn RS, Gorman CA, Johnson CM, Smith TJ. Presence of antibodies in the sera of patients with Graves’ disease recognizing a 23 kDa fibroblast protein. J Clin Endocrinol Metab 1989; 69: 622–628.

    Article  PubMed  CAS  Google Scholar 

  44. Salvi M, Miller A, Wall JR. Human orbital tissue and thyroid membranes express a 64 kDa protein which is recognized by autoantibodies in the serum of patients with thyroid-associated ophthalmopathy. FEBS Letters 1988; 232: 135–139.

    Article  PubMed  CAS  Google Scholar 

  45. Kadlubowski M, Irvine MJ, Rowland AC. The lack of specificity of ophthalmic immunoglobulins in Graves’ disease. J Clin Endocrinol Metab 1986; 63: 990–995.

    Article  PubMed  CAS  Google Scholar 

  46. Kendler DL, Rootman J, Huber GK, Davies TF. A 64 kDa membrane antigen is a recurrent epitope for natural antibodies in patients with Graves’ thyroid and ophthalmic abnormalities. Clin Endocrinol 1991; 35: 539–547.

    Article  CAS  Google Scholar 

  47. Grubeck-Loebenstein B, Trieb K, Sztankay A. et al. Retrobulbar T cells from patients with Graves’ ophthalmopathy are CD8+ and specifically recognize autologous fibroblasts. J Clin Invest 1994; 3: 2738–2743.

    Article  Google Scholar 

  48. Heufelder AE, Smith TJ, Gorman CA, Bahn RS. Increased induction of HLA-DR by interferon-gamma in cultured retroocular fibroblasts derived from patients with Graves’ ophthalmopathy and pretibial dermopathy. J Clin Endocrinol Metab 1991; 73: 307–313.

    Article  PubMed  CAS  Google Scholar 

  49. Heufelder AE, Bahn RS. Modulation of intercellular adhesion molecule-1 (ICAM-1) by cytokines and Graves’ IgGs in cultured Graves’ retroocular fibroblasts. Eur J Clin Invest 1992; 22: 529–537.

    Article  PubMed  CAS  Google Scholar 

  50. Heufelder AE, Wenzel BE, Bahn RS. Cell surface localization of a 72 kilodalton heat shock protein in retroocular fibroblasts from patients with Graves’ ophthalmopathy. J Clin Endocrinol Metab 1992; 74: 732–736.

    Article  PubMed  CAS  Google Scholar 

  51. Heufelder AE, Wenzel BE, Gorman CA, Bahn RS. Detection, cellular localization and modulation of heat shock proteins in cultured fibroblasts from patients with extrathyroidal manifestations of Graves’ disease. J Clin Endocrinol Metab 1991; 73: 739–745.

    Article  PubMed  CAS  Google Scholar 

  52. Morris J, Hay ID, Nelson RE, Jiang Nai S. Clinical utility of thyrotropin receptor antibody assays: Comparison of radioreceptor and bioassay methods. Mayo Clin Proc 1988; 63: 707–712.

    PubMed  Google Scholar 

  53. Heufelder AE, Dutton CM, Sarkar G0. et al. Detection of TSH receptor RNA in cultured fibroblasts from patients with Graves’ ophthalmopathy and pretibial dermopathy. Thyroid 1993; 3: 297–300.

    Article  PubMed  CAS  Google Scholar 

  54. Feliciello A, Porcellini A, Ciullo I. et al. Expression of thyrotropin-receptor mRNA in healthy and Graves’ disease retro-orbital tissue. Lancet 1993; 342: 337–338.

    Article  PubMed  CAS  Google Scholar 

  55. Endo T, Ohno M, Kotani S. et al. Thyrotropin receptor in non-thyroid tissues. Biochem Biophys Res Com 1993; 190: 774–779.

    Article  PubMed  CAS  Google Scholar 

  56. Hiromatsu Y, Sato M, Inoue Y. et al. Localization and clinical significance of thyrotropin receptor mRNA expression in orbital fat and eye muscle tissues from patients with thyroid-associated ophthalmopathy. Thyroid 1997; 6: 553–562.

    Article  Google Scholar 

  57. Heufelder AE. Involvement of the orbital fibroblast and TSH receptor in the pathogenesis of Graves’ ophthalmopathy. Thyroid 1995; 5: 331–340.

    Article  PubMed  CAS  Google Scholar 

  58. Paschke R, Elise R, Vassart G, Ludgate M. Lack of evidence supporting the presence of mRNA for the thyrotropin receptor in extraocular muscle. J Endocrinol Invest 1993; 16: 329–332.

    PubMed  CAS  Google Scholar 

  59. Paschke R, Metcalfe A, Alcalde L. et al. Presence of nonfunctional thyrotropin receptor variant transcripts in retroocular and other tissues. J Clin Endocrinol Metabol 1994; 79: 1232–1233.

    Article  Google Scholar 

  60. Perros P & Kendall-Taylor P. Demonstration of thyrotropin-binding sites in orbital connective tissue: possible role in the pathogenesis of thyroid-associated ophthalmopathy. J Endocrinol Invest 1994; 17: 163–170.

    PubMed  CAS  Google Scholar 

  61. Spitzweg C, Joba W, Hunt N, Heufelder AE. Analysis of human thyrotropin receptor gene expression and immunoreactivity in human orbital tissue. Eur J Endocrinol 1997; 136: 599–607.

    Article  PubMed  CAS  Google Scholar 

  62. Stadlmayr W, Spitzweg C, Bichlmair AM, Heufelder AE. Full length TSH receptor transcripts and TSH receptor-like immunoreactivity in orbital and pretibial fibroblasts of patients with Graves’ ophthalmopathy and pretibial dermopathy. Thyroid 1997; 7:3–12.

    Article  PubMed  CAS  Google Scholar 

  63. Heufelder AE, Bahn RS. Evidence for the presence of a functional TSH receptor in retroocular fibroblasts from patients with Graves’ ophthalmopathy. Exp Clin Endocrinol 1992; 100:62–67.

    Article  PubMed  CAS  Google Scholar 

  64. Paschke R, Vassart G, Ludgate M. Current evidence for and against the TSH receptor being the common antigen in Graves-disease and thyroid-associated ophthalmopathy. Clin Endocrinol 1995; 42:565–9.

    Article  CAS  Google Scholar 

  65. Crisp MS, Lane C, Halliwell M, Wynford Thomas D, Ludgate M. Thyrotropin receptor transcripts in human adipose tissue. J Clin Endocrinol Metab 1997; 82:2003–5.

    PubMed  CAS  Google Scholar 

  66. Sorisky A, Pardasani D, Gagnon A, Smith TJ. Evidence of adipocyte differentiation in human orbital fibroblasts in primary culture. J Clin Endocrinol Metab 1996; 81:3428–31.

    Article  PubMed  CAS  Google Scholar 

  67. Costagliola S, Rodien P, Many M-C, Ludgate M, Vassart G. Genetic immunization against the human thyrotropin receptor causes thyroiditis and allows production of monoclonal antibodies recognizing the native receptor. J Immunol 1998; 160:1458–65.

    PubMed  CAS  Google Scholar 

  68. Costagliola S, Alcalde L, Ruf J, Vassart G, Ludgate M. Overexpression of the extracellular domain of the thyrotropin receptor in bacteria — production of thyrotropin-binding inhibiting immunoglobulins. J Mol Endo 1994; 13:11–21.

    Article  CAS  Google Scholar 

  69. Costagliola S, Many M-C, Stalmans-Falys M, Tonacchera M, Vassart G, Ludgate M. Recombinant TSHR and the induction of autoimmune disease in BALBc mice, a new animal model. Endocrinology 1994; 135:2150–2159.

    Article  PubMed  CAS  Google Scholar 

  70. Costagliola S, Many M-C, Stalmans-Falys M, Vassart G, Ludgate M. The autoimmune response induced by immunizing female mice with the human TSHR varies with the genetic background. Mol Cell Endocrinol 1995; 115:119–206.

    Article  Google Scholar 

  71. Costagliola S, Many M-C, StalmansFalys M, Vassart G, Ludgate M. Transfer of thyroiditis, with syngeneic spleen-cells sensitized with the human thyrotropin receptor, to naive balb/c and nod mice. Endocrinology 1996; 137:4637–4643.

    Article  PubMed  CAS  Google Scholar 

  72. Many M-C, Costagliola S, Detrait M, Denef J-F, Vassart G, Ludgate M. Development of an animal model of autoimmune thyroid eye disease. J Immunol 1999; 162:4966–4974.

    PubMed  CAS  Google Scholar 

  73. Peyster RG, Ginsberg F, Silber JH, Adler LP. Exophthalmos caused by excessive fat: CT volumetric analysis and differential diagnosis. AJNR 1986; 7:35–40.

    Google Scholar 

  74. Forbes G, Gorman CA, Brennan MD, Gehring DG, Ilstrup DM, Earnest F. Ophthalmopathy of GD: computerized volume measurements of the orbital fat and muscle. AJNR 1986; 7:651–656.

    PubMed  CAS  Google Scholar 

  75. Hufnagel TJ, Hickey WJ, Cobbs WH, Jacobiec FA, Iwamoto T, Eagle RC. Immunohistochemical and ultrastructural studies on the exenterated orbital tissues of a patient with GD. Ophthalmology 1987; 91:1411–1419.

    Google Scholar 

  76. Chen X, Hausman DB, Dean RG, Hausman GJ. Differentiation-dependent expression of obese (ob) gene by preadipocytes and adipocytes in primary cultures of porcine stromal-vascular cells. Biochim Biophys Acta 1997; 1359:136–142.

    Article  PubMed  CAS  Google Scholar 

  77. Wiederer O, Löffler. Hormonal regulation of the differentiation of rat adipocyte precursor cells in primary culture. J Lipid Res 1987; 28:649–658.

    PubMed  CAS  Google Scholar 

  78. Rodbell M. Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 1964; 239:375–380.

    PubMed  CAS  Google Scholar 

  79. Kendall-Taylor P, Munro DS. The lipolytic activity of long-acting thyroid stimulator. Biochim Biophys Acta 1971; 231:314–319.

    Article  PubMed  CAS  Google Scholar 

  80. Perros P, Kendall-Taylor P. Demonstration of thyrotropin binding sites in orbital connective tissue: Possible role in the pathogenesis of thyroid-associated ophthalmopathy. J Endocrinol Invest 1994; 17:163–170.

    PubMed  CAS  Google Scholar 

  81. Davies TF, Teng CS, McLachlan SM, Smith BR, Hall R. Thyrotropin receptors in adipose tissue, retro-orbital tissue and lymphocytes. Mol Cell Endocrinol 1978; 9:303–310.

    Article  PubMed  CAS  Google Scholar 

  82. Roselli-Rehfuss L, Robbins LS, Cone RD. Thyrotropin receptor messenger ribonucleic acid is expressed in most brown and white adipose tissues in the guinea pig. Endocrinology 1992; 130:1857–1861.

    Article  PubMed  CAS  Google Scholar 

  83. Mullin BR, Lee G, Ledley FD, Winand RJ, Kohn LD. Thyrotropin interactions with human fat cell membrane preparations and the finding of a soluble thyrotropin binding component. Biochem Biophys Res Commun 1976; 69:55–62.

    Article  PubMed  CAS  Google Scholar 

  84. Marcus C, Ehren H, Bolme P, Arner P. Regulation of lipolysis during the neonatal period: Importance of thyrotropin. J Clin Invest 1988; 82:1793–1797.

    Article  PubMed  CAS  Google Scholar 

  85. Mengistu M, Lukes YG, Nagy EV. et al. TSH receptor expression in retroocular fibroblasts. J Endocrinol Invest 1994; 17:437–441.

    PubMed  CAS  Google Scholar 

  86. Bahn RS, Dutton CM, Natt N, Joba W, Spitzweg C, Heufelder AE. Thyrotropin receptor expression in Graves’ orbital adipose/connective tissues: Potential autoantigen in Graves’ ophthalmopathy. J Clin Endocrinol Metab 1998; 83:998–1002.

    Article  PubMed  CAS  Google Scholar 

  87. Bahn RS, Dutton CM, Joba W, Heufelder AE. Thyrotropin receptor expression in cultured Graves’ orbital preadipocyte fibroblasts is stimulated by thyrotropin. Thyroid 1998; 8:193–196.

    Article  PubMed  CAS  Google Scholar 

  88. Smith TJ, Wang HS, Evans CH. Leukoregulin is a potent inducer of hyaluronan synthesis in cultured human orbital fibroblasts. Am J Physiol 1995; 268:C382–C388.

    PubMed  CAS  Google Scholar 

  89. Smith TJ, Ahmed A, Hogg MG, Higgins PJ. Interferon-gamma is an inducer of plasminogen activator inhibitor type 1 in human orbital fibroblasts. Am J Physiol 1992; 263:C24–C29.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Zentrum für Innere Medizin, Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Endokrinologie, Diabetologie, Klinikum der Philipps-Universität Marburg, Baklingerstrasse, 35033, Marburg, Germany

    Armin E. Heufelder

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  1. Armin E. Heufelder
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  2. Anthony P. Weetman
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  3. Marian Ludgate
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  4. Rebecca S. Bahn
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Editors and Affiliations

  1. Department of Endocrinology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Mark F. Prummel M.D. Ph.D.  & Wilmar M. Wiersinga M.D. Ph.D. (Professor of Endocrinology) &  (Professor of Endocrinology)

  2. Department of Ophthalmology, Orbital Center, University Medical Center Utrecht, Heidelberglaan 100, The Netherlands

    Maarten Ph. Mourits M.D. Ph.D.

  3. Zentrum für Innere Medizin mit Schwerpunkt Gastroenterologie, Endokrinologie, Diabetologie, Klinikum der Philipps-Universität Marburg, Baklingerstrasse, 35033, Marburg, Germany

    Armin E. Heufelder M.D. Ph.D. (Professor of Endocrinology) (Professor of Endocrinology)

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Heufelder, A.E., Weetman, A.P., Ludgate, M., Bahn, R.S. (2000). Pathogenesis of Graves’ ophthalmopathy. In: Prummel, M.F., Wiersinga, W.M., Mourits, M.P., Heufelder, A.E. (eds) Recent Developments in Graves’ Ophthalmopathy. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4647-4_2

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