RESEARCH PAPER
Impact of treatment with methimazole on the Bcl-2 expression in CD8+ peripheral blood lymphocytes in children with Graves’ disease
 
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1
Department of Pediatric Endocrinology and Diabetology,Medical University, Lublin, Poland
2
Department of Clinical Immunology and Immunotherapy, Medical University, Lublin, Poland
 
Ann Agric Environ Med. 2013;20(4):884–888
KEYWORDS:
ABSTRACT:
Introduction and objectives:
The protein product of the proto-oncogene Bcl-2 is a physiological inhibitor of programmed cell death. The results obtained in our previous researches suggest that apoptosis may be involved in the regulation of an immune response in hyperthyroidism. The most common cause of hyperthyroidism is Graves’ disease. The aim of this study was evaluation of expression of Bcl-2 protein in peripheral blood T lymphocytes in hyperthyroid children due to Graves’ disease (GD) before and after therapy with methimazole (MMI), in comparison with healthy controls.

Material and Methods:
Thirty-two children with newly diagnosed hyperthyreosis due to GD before and after 4–6 weeks treatment with MMI, and 20 healthy controls were included into the study. The staining with monoclonal antibodies against CD8 and Bcl-2 was performed within 2 hours after collection, and followed with flow cytometry acquisition and analysis.

Results:
Our study revealed that the expression of Bcl-2 protein in circulating CD8+ T lymphocytes of patients with hyperthyreosis was significantly lower than in healthy controls (p<0.03). The expression of Bcl-2 after 4–6 week therapy with MMI returned to normal level. The difference in Bcl-2 expression between patients after treatment and control group was insignificant.

Conclusions:
The use of MMI in the treatment of hyperthyroidism due to GD leads to the normalization of the Bcl-2 expression on the CD8+ lymphocytes in peripheral blood. Our findings suggest that the changes in the expression of Bcl-2 on the CD8+ cells indicate the involvement of these cells and Bcl-2-regulated apoptotic pathway in the pathogenesis of GD.

 
REFERENCES (25):
1. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002; 87(2): 489–499.
2. Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frölich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004; 292(21): 2591–2599.
3. Aghini-Lombardi F, Antonangeli L, Martino E, Vitti P, Maccherini D, Leoli F, Rago T, Grasso L, Valeriano R, Balestrieri A, Pinchera A. The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano Survey. J Clin Endocrinol Metab. 1999; 84(2): 561–566.
4. Williamson S, Greene SA. Incidence of thyrotoxicosis in childhood: a national population based study in the UK and Ireland. Clin Endocrinol (Oxf). 2010; 72(3): 363–358.
5. Barnes HV, Blizzard RM. Antithyroid drug therapy for toxic diffuse goiter (Graves disease): thirty years experience in children and adolescents. J Pediatr. 1977; 91(2): 313–320.
6. Poyrazoğlu S, Saka N, Bas F, Isguven P, Dogu A, Turan S, Bereket A, Sarikaya S, Adal E, Cizmecioglu F, Saglam H, Ercan O, Memioglu N, Günöz H, Bundak R, Darendeliler F, Yildiz M, Guran T, Akcay T, Akin L, Hatun S. Evaluation of diagnosis and treatment results in children with Graves’ disease with emphasis on the pubertal status of patients. J Pediatr Endocrinol Metab. 2008; 21(8): 745–751.
7. Zimmerman MB. Iodine deficiency. Endocr Rev. 2009; 30(4): 376–408.
8. Vanderpump MPJ. The epidemiology of thyroid diseases. In: Braverman LE, Utiger RD (eds). Werner and Ingbar’s The Thyroid: A Fundamental and Clinical Text, 9th edn. JB Lippincott-Raven: Philadelphia, 2005, 398–496.
9. Flynn RV, MacDonald TM, Morris AD, Jung RT, Leese GP. The thyroid epidemiology, audit and research study; thyroid dysfunction in the general population. J Clin Endocrinol Metab. 2004; 89(8): 3879–3884.
10. Leese GP, Flynn RV, Jung RT, Macdonald TM, Murphy MJ, Morris AD. Increasing prevalence and incidence of thyroid disease in Tayside, Scotland: The Thyroid Epidemiology, Audit and Research Study (TEARS). Clin Endocrinol (Oxf). 2008; 68(2): 311–316.
11. Vanderpump MP. The epidemiology of thyroid disease. Br Med Bull. 2011; 99: 39–51. doi: 10.1093/bmb/ldr030.
12. Mills KH. Regulatory T cells: friend or foe in immunity to infection? Nat Rev Immunol. 2004; 4(11): 841–855.
13. Pericolini E, Alunno A, Gabrielli E, Bartoloni E, Cenci E, Chow SK, Bistoni G, Casadevall A, Gerli R, Vecchiarelli A. The microbial capsular polysaccharide galactoxylomannan inhibits IL-17A production in circulating T cells from rheumatoid arthritis patients. PLoS One. 2013; 8(1): e53336.
14. Klatka M, Grywalska E, Surdacka A, Tarach J, Klatka J, Roliński J. Peripheral blood lymphocyte apoptosis and its relationship with thyroid function tests in adolescents with hyperthyroidism due to Graves’ disease. Arch Med Sci. 2012; 8(5): 865–873.
15. Martinou JC, Youle RJ. Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell. 2011; 21(1): 92–101.
16. Bossowski A, Czarnocka B, Bardadin K, Urban M, Niedziela M, Dadan J. Expression of Bcl-2 family proteins in thyrocytes from young patients with immune and nonimmune thyroid diseases. Horm Res. 2008; 70(3): 155–164.
17. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002; 2(9): 647–656.
18. Giordano C, Richiusa P, Bagnasco M, Pizzolanti G, Di Blasi F, Sbriglia MS, Mattina A, Pesce G, Montagna P, Capone F, Misiano G, Scorsone A, Pugliese A, Galluzzo A. Differential regulation of Fas-mediated apoptosis in both thyrocyte and lymphocyte cellular compartments correlates with opposite phenotypic manifestations of autoimmune thyroid disease. Thyroid. 2001; 11(3): 233–244.
19. Xu WC, Chen SR, Huang JX, Zheng ZC, Chen LX, Lin JJ, Li YG. Expression and distribution of S-100 protein, CD83 and apoptosis-related proteins (Fas, FasL and Bcl-2) in thyroid tissues of autoimmune thyroid diseases. Eur J Histochem. 2007; 51(4): 291–300.
20. Volpe R. The immunomodulatory effects of anti-thyroid drugs are mediated via actions on thyroid cells, affecting thyrocyte-immunocyte signalling: a review. Curr Pharm Des. 2001; 7(6): 451–460.
21. Hodkinson CF, Simpson EE, Beattie JH, O’Connor JM, Campbell DJ, Strain JJ, Wallace JM. Preliminary evidence of immune function modulation by thyroid hormones in healthy men and women aged 55–70 years. J Endocrinol. 2009; 202(1): 55–63.
22. Crescioli C, Cosmi L, Borgogni E, Santarlasci V, Gelmini S, Sottili M, Sarchielli E, Mazzinghi B, Francalanci M, Pezzatini A, Perigli G, Vannelli GB, Annunziato F, Serio M. Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes. J Endocrinol. 2007; 195(1): 145–155.
23. Mitsiades N, Poulaki V, Tseleni-Balafouta S, Chrousos GP, Koutras DA. Fas ligand expression in thyroid follicular cells from patients with thionamide-treated Graves’ disease. Thyroid. 2000; 10(7): 527–532.
24. Myśliwiec J, Okota M, Nikołajuk A, Górska M. Soluble Fas, Fas ligand and Bcl-2 in autoimmune thyroid diseases: relation to humoral immune response markers. Adv Med Sci. 2006; 51(1): 119–122.
25. Jiskra J, Antosová M, Límanová Z, Telicka Z, Lacinová Z. The relationship between thyroid function, serum monokine induced by interferon gamma and soluble interleukin-2 receptor in thyroid autoimmune diseases. Clin Exp Immunol. 2009; 156(2): 211–216.
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