The role of circulating sTWEAK in the pathogenesis of Hashimoto's thyroiditis - a pilot study.

INTRODUCTION We aimed to investigate the role of sTWEAK in the pathogenesis of Hashimoto's thyroiditis, which is a chronic inflammatory autoimmune disease. MATERIAL AND METHODS A total of 80 patients were included in the study, 60 of whom were newly diagnosed with Hashimoto's thyroiditis (20 patients in each of the euthyroid, subclinical hypothyroid, and overt hypothyroid subgroups), and 20 of whom were healthy volunteers. Thyroid function tests and autoantibodies were measured using the electro-chemiluminescence immunoassay method, and sTWEAK, IL-17A, IL-12, and TGF-beta1 were measured using enzyme-linked immunosorbent assay method. RESULTS The Hashimoto's Thyroiditis group had lower levels of sTWEAK and TGF-beta1, but had higher levels of IL-12 and IL-17A as compared to the control group. Of these, only the difference between IL-17A levels reached statistical significance (2.1 pg/mL vs. 1.8 pg/mL, respectively; p < 0.001). While the levels of sTWEAK were similar in the control, euthyroid, and subclinical groups, the overt hypothyroidism group had lower level of sTWEAK than that of subclinical hypothyroidism (687.6 ± 153.3 pg/mL vs. 888.2 ± 374.4 pg/mL, respectively; p = 0.03). A negative correlation was determined between sTWEAK level and anti-TPO (r = -0.533, p = 0.028) and IL-17A (r = -0.600, p = 0.005) levels in the overt hypothyroidism group. CONCLUSIONS The reduced levels of sTWEAK with progression of Hashimoto's Thyroiditis and the significant correlation between the sTWEAK levels and anti-TPO found in this study suggest that sTWEAK plays an active role in chronic inflammation in the pathogenesis of Hashimoto's Thyroiditis and in the progression of autoimmunity. (Endokrynol Pol 2016; 67 (6): 562-566).

[1]  K. Baskoy,et al.  Endothelial dysfunction, insulin resistance and inflammation in congenital hypogonadism, and the effect of testosterone replacement. , 2015, Endocrine journal.

[2]  F. Dede,et al.  The relationship between asymptomatic organ damage, and serum soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and Interleukin-17A (IL-17A) levels in non-diabetic hypertensive patients , 2014, BMC Nephrology.

[3]  P. Heydarpour,et al.  A Further TWEAK to Multiple Sclerosis Pathophysiology , 2014, Molecular Neurobiology.

[4]  J. Vendrell,et al.  TWEAK: A New Player in Obesity and Diabetes , 2013, Front. Immunol..

[5]  M. Khrestchatisky,et al.  Is TWEAK a Biomarker for Autoimmune/Chronic Inflammatory Diseases? , 2013, Front. Immunol..

[6]  Foad Katirai,et al.  Th17 cell plays a role in the pathogenesis of Hashimoto's thyroiditis in patients. , 2013, Clinical immunology.

[7]  I. Manolova,et al.  Serum levels of transforming growth factor-β1 (TGF-β1) in patients with systemic lupus erythematosus and Hashimoto's thyroiditis. , 2013, European cytokine network.

[8]  H. Xu,et al.  T cell‐derived leptin contributes to increased frequency of T helper type 17 cells in female patients with Hashimoto's thyroiditis , 2013, Clinical and experimental immunology.

[9]  M. Ren,et al.  The role of TWEAK/Fn14 in cardiac remodeling , 2012, Molecular Biology Reports.

[10]  F. Sánchez‐Madrid,et al.  Increased circulating pro-inflammatory cytokines and Th17 lymphocytes in Hashimoto's thyroiditis. , 2010, The Journal of clinical endocrinology and metabolism.

[11]  J. Egido,et al.  The CD163-expressing macrophages recognize and internalize TWEAK: potential consequences in atherosclerosis. , 2009, Atherosclerosis.

[12]  B. Rovin,et al.  Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study , 2009, Arthritis research & therapy.

[13]  A. Gelincik,et al.  The relationship between transforming growth factor-beta1, vascular endothelial growth factor, nitric oxide and Hashimoto's thyroiditis. , 2009, International immunopharmacology.

[14]  T. Zheng,et al.  No end in site: TWEAK/Fn14 activation and autoimmunity associated‐ end‐organ pathologies , 2008, Journal of leukocyte biology.

[15]  A. Comlekçi,et al.  Hashimoto's thyroiditis, but not treatment of hypothyroidism, is associated with altered TGF-beta1 levels. , 2008, Archives of medical research.

[16]  T. Zheng,et al.  TWEAKing tissue remodeling by a multifunctional cytokine: role of TWEAK/Fn14 pathway in health and disease. , 2007, Cytokine.

[17]  A. Gritzapis,et al.  Th1 and Th2 Serum Cytokine Profiles Characterize Patients with Hashimoto’s Thyroiditis (Th1) and Graves’ Disease (Th2) , 2004, Neuroimmunomodulation.

[18]  A. Berger Th1 and Th2 responses: what are they? , 2000, BMJ : British Medical Journal.

[19]  A. Cerwenka,et al.  TGF-β1: immunosuppressant and viability factor for T lymphocytes , 1999 .

[20]  S. Fukata,et al.  Increased serum concentration of interleukin-12 in patients with silent thyroiditis and Graves' disease. , 1999, Thyroid : official journal of the American Thyroid Association.

[21]  F. Trimarchi,et al.  Serum interleukin-23 (IL-23) is increased in Hashimoto's thyroiditis. , 2014, Endocrine journal.

[22]  M. Niedziela,et al.  The role of the immune system and cytokines involved in the pathogenesis of autoimmune thyroid disease (AITD). , 2014, Endokrynologia Polska.

[23]  M. Moniuszko,et al.  [Evaluation of CD4+CD161+CD196+ and CD4+IL-17+ Th17 cells in the peripheral blood of young patients with Hashimoto's thyroiditis and Graves' disease]. , 2012, Pediatric endocrinology, diabetes, and metabolism.

[24]  D. Solomon and Graves' Disease , 2006 .

[25]  A. Cerwenka,et al.  TGF-beta1: immunosuppressant and viability factor for T lymphocytes. , 1999, Microbes and infection.