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Review article: Biomedical intelligence

Vol. 147 No. 3132 (2017)

Personalised immunomodulating treatments for Graves’ disease: fact or fiction?

DOI
https://doi.org/10.4414/smw.2017.14476
Cite this as:
Swiss Med Wkly. 2017;147:w14476
Published
03.08.2017

Summary

Although Graves’ disease has been recognised for more than 100 years, its physiopathological mechanisms are incompletely understood. Treatment strategies today mainly focus on suppression of thyroid hormone production by use of antithyroid drugs or radio-iodine, but neglect the underlying immunological mechanisms. Although Graves’ disease is often seen as a prototype for an autoimmune mechanism, it is more likely to be a heterogeneous syndrome showing characteristics of both autoimmunity and immunodeficiency. The interplay of these two mechanisms may well characterise the physiopathology of this disease and its complications. Immunodeficiency may be either genetically determined or secondarily acquired. Various triggering events lead to autoimmunity with stimulation of the thyroid gland resulting in the clinical syndrome of hyperthyroidism. Also, relapse risk differs from patient to patient and can be estimated from clinical parameters incorporated into the Graves’ Recurrent Events After Therapy (GREAT) score. Accurate risk stratification may help to distinguish high-risk patients for whom a more definitive treatment approach should be used from others where there is a high probability that the disease will recover with medical treatment alone. Several smaller trials having found positive effects of immunosuppressive drugs on recurrence risk in Graves’ disease; therefoore, there is great potential in the use of novel immunomodulating drugs in addition to the currently used antithyroid drugs for the successful treatment of this condition. Further in-depth exploration of susceptibility, triggering factors and immunological mechanisms has the potential to improve treatment of Graves’ disease, with more personalised, risk-adapted treatment strategies based on the different physiopathological concepts of this heterogeneous condition.

References

  1. Weetman AP. Grave’s disease 1835-2002. Horm Res. 2003;59(Suppl 1):114–8.
  2. Hargreaves CE, Grasso M, Hampe CS, Stenkova A, Atkinson S, Joshua GW, et al. Yersinia enterocolitica provides the link between thyroid-stimulating antibodies and their germline counterparts in Graves’ disease. J Immunol. 2013;190(11):5373–81. doi:.https://doi.org/10.4049/jimmunol.1203412
  3. Struja T, Guebelin L, Kutz A, Fehlberg H, Mueller B, Schuetz P. Does Immunosuppressive Therapy Improve Outcomes in Graves’ Disease? A Systematic Review and Meta-Analysis. Thyroid. 2016;26(5):634–40. doi:.https://doi.org/10.1089/thy.2015.0647
  4. Allenspach E, Torgerson TR. Autoimmunity and Primary Immunodeficiency Disorders. J Clin Immunol. 2016;36(S1, Suppl 1):57–67. doi:.https://doi.org/10.1007/s10875-016-0294-1
  5. Grimbacher B, Warnatz K, Yong PFK, Korganow A-S, Peter H-H. The crossroads of autoimmunity and immunodeficiency: Lessons from polygenic traits and monogenic defects. J Allergy Clin Immunol. 2016;137(1):3–17, quiz 18. doi:.https://doi.org/10.1016/j.jaci.2015.11.004
  6. Franklyn JA, Boelaert K. Thyrotoxicosis. Lancet. 2012;379(9821):1155–66. doi:.https://doi.org/10.1016/S0140-6736(11)60782-4
  7. Abraham P, Avenell A, McGeoch SC, Clark LF, Bevan JS. Antithyroid drug regimen for treating Graves’ hyperthyroidism. Cochrane Database Syst Rev. 2010;CD003420(1):CD003420. doi:.https://doi.org/10.1002/14651858.CD003420.pub4
  8. Orgiazzi J. Thyroid autoimmunity. Presse Med. 2012;41(12 P 2):e611–25. doi:.https://doi.org/10.1016/j.lpm.2012.10.002
  9. Struja T, Fehlberg H, Kutz A, Guebelin L, Degen C, Muller B, et al. Can we predict relapse in Graves’ disease? Results from a Systematic Review and Meta-analysis. Eur J Endocrinol. 2017;176(1):87–97. doi:.https://doi.org/10.1530/EJE-16-0725
  10. Vos XG, Endert E, Zwinderman AH, Tijssen JGP, Wiersinga WM. Predicting the Risk of Recurrence Before the Start of Antithyroid Drug Therapy in Patients With Graves’ Hyperthyroidism. J Clin Endocrinol Metab. 2016;101(4):1381–9. doi:.https://doi.org/10.1210/jc.2015-3644
  11. Struja T, Kaeslin M, Boesiger F, Jutzi R, Imahorn N, Kutz A, et al. External validation of the GREAT score to predict relapse risk in Graves’ disease: results from a multicenter, retrospective study with 741 patients. Eur J Endocrinol. 2017;176(4):413–9. doi:.https://doi.org/10.1530/EJE-16-0986
  12. Brix TH, Kyvik KO, Christensen K, Hegedüs L. Evidence for a major role of heredity in Graves’ disease: a population-based study of two Danish twin cohorts. J Clin Endocrinol Metab. 2001;86(2):930–4. doi:.https://doi.org/10.1210/jcem.86.2.7242
  13. Brix TH, Hegedüs L. Twin studies as a model for exploring the aetiology of autoimmune thyroid disease. Clin Endocrinol (Oxf). 2012;76(4):457–64. doi:.https://doi.org/10.1111/j.1365-2265.2011.04318.x
  14. Hall R, Stanbury JB. Familial studies of autoimmune thyroiditis. Clin Exp Immunol. 1967;2:719–25.
  15. Bona G, Defranco S, Chiocchetti A, Indelicato M, Biava A, Difranco D, et al. Defective function of Fas in T cells from paediatric patients with autoimmune thyroid diseases. Clin Exp Immunol. 2003;133(3):430–7. doi:.https://doi.org/10.1046/j.1365-2249.2003.02221.x
  16. Salmaso C, Bagnasco M, Pesce G, Montagna P, Brizzolara R, Altrinetti V, et al. Regulation of apoptosis in endocrine autoimmunity: insights from Hashimoto’s thyroiditis and Graves’ disease. Ann N Y Acad Sci. 2002;966(1):496–501. doi:.https://doi.org/10.1111/j.1749-6632.2002.tb04253.x
  17. Fountoulakis S, Vartholomatos G, Kolaitis N, Frillingos S, Philippou G, Tsatsoulis A. Differential expression of Fas system apoptotic molecules in peripheral lymphocytes from patients with Graves’ disease and Hashimoto’s thyroiditis. Eur J Endocrinol. 2008;158(6):853–9. doi:.https://doi.org/10.1530/EJE-08-0092
  18. Bacchetta R, Barzaghi F, Roncarolo MG. From IPEX syndrome to FOXP3 mutation: a lesson on immune dysregulation. Ann N Y Acad Sci. 2016 Feb 25 [epub ahead of print]. doi:.https://doi.org/10.1111/nyas.13011
  19. Chistiakov DA, Chistiakova EI, Voronova NV, Turakulov RI, Savost’anov KV. A variant of the Il2ra / Cd25 gene predisposing to graves’ disease is associated with increased levels of soluble interleukin-2 receptor. Scand J Immunol. 2011;74(5):496–501. doi:.https://doi.org/10.1111/j.1365-3083.2011.02608.x
  20. Wang Z, Fan X, Zhang R, Lin Z, Lu T, Bai X, et al. Integrative analysis of mRNA and miRNA array data reveals the suppression of retinoic acid pathway in regulatory T cells of Graves’ disease. J Clin Endocrinol Metab. 2014;99(12):E2620–7. doi:.https://doi.org/10.1210/jc.2014-1883
  21. Singh K, Chang C, Gershwin ME. IgA deficiency and autoimmunity. Autoimmun Rev. 2014;13(2):163–77. doi:.https://doi.org/10.1016/j.autrev.2013.10.005
  22. Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, et al. Selective IgA deficiency in autoimmune diseases. Mol Med. 2011;17(11-12):1383–96. doi:.https://doi.org/10.2119/molmed.2011.00195
  23. Mohammadi J, Ramanujam R, Jarefors S, Rezaei N, Aghamohammadi A, Gregersen PK, et al. IgA deficiency and the MHC: assessment of relative risk and microheterogeneity within the HLA A1 B8, DR3 (8.1) haplotype. J Clin Immunol. 2010;30(1):138–43. doi:.https://doi.org/10.1007/s10875-009-9336-2

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