The Adaptive Immune Response in Graves’ Disease: Does Vitamin D have a role?

Authors

  • Dyah Purnamasari Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Indonesia
  • Pradana Soewondo Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Indonesia
  • Samsuridjal Djauzi Division of Immunology, Department of Medicine, Faculty of Medicine, University of Indonesia

Abstract

Graves' disease (GD) is an autoimmune disease characterized by excessive autoantibody formation by the lymphocyte B cells (B cells). The autoantibodies will bind to Thyroid Stimulating Hormone receptors (TSHR) and enhance the production of thyroid hormone.  Previous studies indicate that the impairment of immune response in GD happens in several points in the adaptive immune response, particularly the profile of the intrathyroidal dendritic cells (tDC), the imbalance of T helper-1 (Th1) and T helper-2 (Th2), the Th17 cells that act as pro-inflammatory cells and the dysfunction of immune modulating T regulator (Treg) cells.6-11

 

Vitamin D is a steroid hormone which has pleiotropic effects. The role of vitamin D in bone and calcium metabolism is already established. The discovery of vitamin D receptor (VDR) in immune cells such as monocytes/macrophages, T cells and B cells, demonstrates that vitamin D may influence innate and adaptive immune process. Recent studies try to explore the relationship between vitamin D and autoimmune disease, furthermore they consider vitamin D as a modifiable environmental factor in autoimmune diseases.13,40 Most people with autoimmune diseases have lower vitamin D level than that of healthy subjects. Vitamin D level also has been associated with disease activity of Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA).

 

Vitamin D influences adaptive immune response through its ability to modulate dendritic Cells (DC), T cells, B cells and Treg cells. Although previous studies reported the immune response disturbance in GD include the tDC, Thelper and Treg cells,6-11 little is known whether the immunoregulatory effect of vitamin D can interfere with the natural history of GD. The effect of vitamin D in GD remains to be explored.

Downloads

Download data is not yet available.

References

Weetman AP. Graves' disease. N Engl J Med. 2000;343(17):1236-48.

Weetman AP, McGregor AM, Hall R. Evidence for an effect of antithyroid drugs on the natural history of Graves' disease. Clin Endocrinol (Oxf).

;21:163-72.

Cooper DS. Hyperthyroidism. The Lancet. 2003;362:459-68.

Orgiazzi J. Thyroid autoimmunity. Presse Med. 2012;41:e611-25.

Swain M, Swain T, Mohanty BK. Autoimmune thyroid disorders-An update. Indian Journal of Clinical Biochemistry. 2005;21(1):9-17.

Heuer M, Aust G, Ode-Hakim S, Scherbaum WA. Different cytokine mRNA profiles in Graves' disease, Hashimoto's thyroiditis, and nonautoimmune thyroid

disorders determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Thyroid. 1996;6(2):97-106.

Nagayama Y, Saitoh O, Mclachlan SM, Rapoport B, Kano H, Kumazawa Y. TSH receptor-adenovirus-induced Graves' hyperthyroidism is attenuated in both

interferon-γ and interleukin-4 knockout mice; implication for the Th1/Th2 paradigm. Clin Exp Immunol. 2004;138:417-22.

Nanba T, Watanabe M, Inoue N, Iwatani Y. Increases of the Th1/Th2 cell ratio in severe Hashimoto's disease and in the proportion of Th17 cells in

intractable Graves' disease. Thyroid. 2009;19(6):495-.

Phenekos C, Vryonidou A, Gritzapis AD, Baxevanis CN, Goula M, Papamichail M. Th1 and Th2 serum cytokine profiles characterize patients with Hashimoto's

thyroiditis (Th1) and Graves' disease (Th2). Neuroimmunomodulation. 2004;11:209-13.

Quadbeck B, Eckstein AK, Tews S, Walz M, Hoermann R, Mann K, et al. Maturation of thyroidal dendritic cells in Graves' Disease. Scand J Immunol.

;55:612-20.

Kabel PJ, Voorbij HAM, Haan MD, Gaag RDVD, Drexhage HA. Intrathyroidal dendritic cells. J Clin Endocrinol Metab. 1988;65:199-207.

Adams JS, Liu PT, Chun R, Modlin RL, Hewison M. Vitamin D in the defense of the human immune response. Ann NYAcadSci. 2007;1117:94-105.

Adorini L, Penna G. Control of autoimmune diseases by the vitamin D endocrine system. Nature Clinical Practice Rheumatology. 2008;4(8):404-12.

Aranow C. Vitamin D and the immune system. J Investig Med. 2011;59(6):881-6.

Brown AJ, Dusso A, Slatopolsky E. Vitamin D. Am J Physiol Renal Physiol. 1999;277:157-75.

DeLuca H. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004;80:1689s-96s.

Etten Ev, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: Basic concepts. Journal of Steroid Biochemistry & Molecular Biology.

;97:93-101.

Cantorna MT, Mahon BD. Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Experimental Biology and

Medicine. 2004;229:1136-42.

Bartels LE, Bendix M, Hvas CL, Jorgensen SP, Agnholt J, Agger R, et al. Oral vitamin D3 supplementation reduces monocyte-derived dendritic cell

maturation and cytokine production in Crohn's disease patients. Inflammopharmacol. 2013.

Yamashita H, Noguchi S, KeisukeTakatsu, Koike E, Murakami T, Watanabe S, et al. High prevalence of vitamin D deficiency in Japanese female patients

with Graves' disease. Endocrine Journal. 2001;48(1):63-9.

Yasuda T, Okamoto Y, Hamada N, Miyashita K, Takahara M, Sakamoto F, et al. Serum vitamin D levels are decreased in patients without remission of

Graves' disease. Endocrine. 2013;43:230-2.

Yasuda T, Okamoto Y, Hamada N, Miyashita K, Takahara M, Sakamoto F, et al. Serum vitamin D levels are decreased and associated with thyroid volume in

female patients with newly onset Graves' disease. Endocrine. 2012;42:739-41.

Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-81.

Dusso AS, Brown AJ, 2005;289:8-28. SEAJPRP. Vitamin D. Am J Physiol Renal Physiol. 2005;289:8-28.

Kulie T, Groff A, Redmer J, Hounshell J, S S. Vitamin D: An evidence-based review. J Am Board Fam Med. 2009:698-706.

Zittermann A. Vitamin D in preventive medicine: Are we ignoring the evidence? British Journal of Nutrition. 2003;89:552-72.

Li J, Byrne ME, Chang E, Jiang Y, Donkin SS, Buhman KK ea-. 1, 25-dihidroxyvitamin D hidroxylase in adipocytes. J Steroid BiochemMol Biol.

;112:122-6.

Ogunkolade BW, Boucher BJ, Prahl JM, Bustin SA, Burrin JM, Noonan K ea-. Vitamin D receptor (VDR) mRNA and VDR protein levels in relation to vitamin D

status, insulin secretory capacity and VDR genotype in Bangladeshi Asians. . Diabetes. 2002;51:2294-312.

Yetley E. Assessing the vitamin D status of the US population. Am J ClinNutr 2008;88:558S-64S.

Hagenau T, Vest R, Gissel TN, Poulsen CS, Erlandsen M, Mosekilde L, et al. Global vitamin D levels in relation to age, gender, skin pigmentation and

latitude: An ecologic meta-regression analysis. Osteoporos Int. 2009;20:133-40.

Mithal A, Wahl DA, Bonjour JP, Burckhardt P, Dawson-Hughes B, Eisman JA, et al. Global vitamin D status and determinants of hypovitaminosis D.

Osteoporosis Int. 2009;20:1807-20.

Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: Modulator of the immune system. Current Opinion in Pharmacology. 2010;10:482-96.

Berer A, Stockl J, Majdic O, Wagner T, Kollars M, Lechner K, et al. 1,25-dihydroxyvitamin D3 inhibits dendritic cell differentiation and maturation in

vitro. Experimental Hematology. 2000;28:575-83.

Piemonti L, Monti P, Marina S, Fraticelli P, Leone BE, Cin ED, et al. Vitamin D3 affects differentiation, maturation and function of human

monocyte-derived dendritic cells. Journal of Immunology. 2000;164:4443-51.

Handono K, Daramatasia W, Pratiwi, Sunarti S, Wahono S, Kalim H. Low level of vitamin D increased dendritic cell maturation and expression of

interferon-γ and interleukin-4 in systemic lupus erythematosus. Journal of pharmacy and biological sciences. 2012;2(4):37-43.

Jeffery LE, Burke F, Mura M, Zheng Y, Qureshi OS, al. HMe. 1,25-dihydroxyvitamin D3 and interleukin-2 combine to inhibit T cell production of

inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FozP3. J Immunol 2009;183:5458-67.

Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HFJ, O'Garra A. 1α,25-dihydroxyvitamin D3 has a direct effect on naive CD4+ to enhance the

development of Th2 cells. The Journal of Immunology. 2001;167:4974-80.

Mahon BD, Wittke A, Weaver V, Cantorna MT. The targets of vitamin D depend on the differentiation and activation status of CD4+ T cells. J

Cell Biochem. 2003;89:922-32.

Heine G, Niesner U, Chang H-D, Steinmeyer A, Zugel U, Zuberbier T, et al. 1,25-dihydroxyvitamin D3 promotes IL-10 production in human B cells. Eur J

Immunol. 2008;38:2210-8.

Schwalfenberg GK. Solar radiation and vitamin D: Mitigating environmental factors in autoimmune disease. Journal of Environmental and Public Health.

:1-9.

Kriegel MA, Manson JE, Costenbader KH. Does vitamin D affect risk of developing autoimmune disease?: A sytematic review. Semin Arthritis Rheum.

;40:512-31.

Antico A, Tampoia M, Tozzoli R, Bizzaro N. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune disease? A systematic

review of the literature. Autoimmune Rev. 2012;12(2):127-36.

Holick MF. Sunlight and vitamin D for bone health and prevention ofautoimmune disease, cancers and cardiovascular disease. Am J Clin Nutr

;80:1678s-88s.

Leventis P, Patel S. Clinical aspects of vitamin D in the management of rheumatoid arthritis. Rheumatology. 2008;47:1617-21.

Handono K, Gani AA, Ekawati M, Wahono S. Serum level of vitamin D and autoantibodies level in systemic lupus erythematosus (SLE) patients. Journal of

Pharmacy and Biological Sciences. 2012;3(4):16-20.

Bartels LE, Jogersen SP, Bendix M, Hvas CL, Agnholt J, Agger R, et al. 25-Hydroxy vitamin D3 modulates dendritic cell phenotype and function in Crohn’s

disease. Inflammopharmacol. 2013;21:177-86.

Ben-Zvi I, Aranow C, Mackay M, Stanevsky A, Kamen DL, Marinescu LM, et al. The impact of vitamin D on dendritic cell function in patients with systemic

lupus erythematosus. Plos ONE. 2010;5(2):1-8.

Vasu C, Holterman MJ, Prabhakar B. Modulation of dendritic cell function and cytokine production to prevent thyroid autoimmunity. Autoimmunity.

;36(6-7):389-96.

Kawashima A, Tanigawa K, Akama T, Yoshihara A, Ishii N, Suzuki K. Innate immune activation and thyroid autoimmunity. J Clin Endocrinol Metab.

;96:3661-71.

Tsokos GC, Goust J-M, Virella G. Tolerance and autoimmunity. In: Virella G, editor. Medical Immunology. 5th ed. New York: Marcel Dekker; 2001. p.

-40.

Steinman RM, Hawiger D, Liu K, Bonifaz L, Bonnyay D, Mahnke K, et al. Dendritic cell function in vivo during the steady state: A role in peripheral

tolerance. Ann N Y Acad Sci. 2003;987:15-25.

Moser M. Antigen presentation, dendritic cells and autoimmunity In: Rose NR, Mackay IR, editors. The Autoimmune Disease. 4th ed. UK: Elsevier Academic

Press; 2006. p. 37-46.

Shortman K, Liu Y-J. Mouse and human dendritic cell subtypes. Nature Reviews. 2002;2:151-61.

Prabhakar BS, Bahn RS, Smith TJ. Current perspective on the pathogenesis of Graves’ disease and ophthalmopathy. Endocrine Reviews 2003;24(6):802-35.

Weetman AP, DeGroot LJ. Autoimmunity to the thyroid gland. Thyroid Manager. 2013:1-127.

Mao C, Wang S, Xiao Y, Xu J, Jiang Q, Jin M, et al. Impairment of regulatory capacity of CD4+CD25+ regulatory T cells mediated by dendritic cell

polarization and hyperthyroidism in Graves' disease. The Journal of Immunology. 2011;186:4734-43.

Zhou H, Xu C, Gu M. Vitamin D receptor (VDR) gene polymorphisms and Graves' disease: A meta-analysis. Clin Endocrinol (Oxf). 2009;70(6):938-45.

Pantazi H, PD P. Changes in parameters of bone and mineral metabolism during therapy for hyperthyroidism. J Clin Endocrinol Metab. 2000;85:1099-106.

Misharin A, Hewison M, Chen C-R, Lagishetty V, Aliesky HA, Mizuturi Y, et al. Vitamin D deficiency modulates Graves' hyperthyroidism induced in BALB/c

mice by thyrotropin receptor immunization. Endocrinology. 2009;150(2):1051-60.

Kawakami-Tani T, EtsushiFukawa, Tanaka H, Abe Y, Makino I. Effect of lα-Hydroxyvitamin D3 on serum levels of thyroid bormones in hyperthyroid patients

with untreated Graves' Disease. Metabolism. 1997:1184-118.

Published

2014-05-31

How to Cite

Purnamasari, D., Soewondo, P., & Djauzi, S. (2014). The Adaptive Immune Response in Graves’ Disease: Does Vitamin D have a role?. Journal of the ASEAN Federation of Endocrine Societies, 29(1), 8. Retrieved from https://asean-endocrinejournal.org/index.php/JAFES/article/view/110

Issue

Section

Review Articles