Evaluation of serum neopterin levels in patients with Graves disease

Yıl 2023, Cilt: 4 Sayı: 5, 418 - 422, 27.10.2023

Sinem Gürcü Göknur Yorulmaz Evin Kocatürk Hatice Hamarat Melisa Şahin Tekin Yeşim Kaya Yaşar İ. Özkan Alataş

https://doi.org/10.47582/jompac.1345829

Öz

Aim: Graves' disease is a disease with an autoimmune basis in which the synthesis and release of thyroid hormone from the thyroid gland increases. Interferon-gamma (IFN-γ) released from activated T lymphocytes causes macrophages to produce neopterin (NPT), increasing its concentration in serum and other body fluids. There is a relationship between NPT and the production of free oxygen radicals by these cells. In this study, it was aimed to measure serum NPT levels in individuals with Graves' disease.
Material and Method: The study included 13 newly diagnosed Graves' patients (neopterin levels were measured at the time of first diagnosis and at the 3rd month of treatment) and 16 Graves' patients who were followed up in endocrinology outpatient clinics for at least one year. NPT levels of 23 healthy individuals without any disease were taken as the control group. Free triiodothyronine (T3), free thyroxine (T4), thyroglobulin, and thyroid stimulating hormone (TSH) levels were measured in the blood samples of the participants.
Results: Serum NPT levels were found to be higher in Graves' patients compared to the control group (6.66 nmol/L in newly diagnosed patients, 9.24 nmol/L in patients at the 3rd month of treatment, 10.68 nmol/L in patients followed for one year or more, 1.44 nmol/L in the control group, respectively, p <0.05).
Conclusion: Monitoring NPT levels in serum and other body fluids can be used to evaluate the diagnosis, prognosis, and treatment efficacy of autoimmune diseases. In addition, NPT can be suggested as a potential biomarker to determine disease stage, treatment efficacy, and immunological remission status, as well as the diagnosis of Graves' disease.

Anahtar Kelimeler

Neopterin, Graves disease, Hyperthyroidism, Cellular immunity, T helper cells.

Destekleyen Kurum

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Graves hastalığında serum neopterin düzeylerinin değerlendirilmesi

Öz

Amaç: Graves hastalığı tiroid bezinden tiroid hormonunun sentez ve salınımının arttığı otoimmün temelleri olan bir hastalıktır. Aktive edilmiş T lenfositlerinden salınaninterferon-gamma ( IFN-γ), makrofajların neopterin (NPT) üretmesine ve bunun serum ve diğer vücut sıvılarındaki konsantrasyonunu artırmasına neden olur. NPT ile bu hücrelerin serbest oksijen radikalleri üretmesi arasında bir ilişki vardır. Bu çalışmada Graves hastalığı olan bireylerde serum NPT düzeylerinin ölçülmesi amaçlandı.
Gereç ve Yöntem: Çalışmaya, 13 yeni tanı almış Graves hastası (ilk tanı anında ve tedavinin 3. ayında neopterin düzeyi bakıldı) ve endokrinoloji polikliniklerinde en az bir yıldır takip edilen 16 Graves hastası dahil edildi. Herhangi bir hastalığı olmayan 23 sağlıklı bireyin NPT düzeyleri bakılarak kontrol grubu olarak alındı. Katılımcıların kan örneklerinde serbest triiyodotironin (T3), serbest tiroksin (T4), tiroglobulin ve tiroid uyarıcı hormon (TSH) düzeyleri ölçüldü.
Bulgular: Serum NPT seviyeleri Graves hastalarında kontrol grubuna göre daha yüksek bulundu (sırasıyla yeni tanı alanlarda 6,66 nmol/L:,tedavinin 3. Ayındaki hastalarda 9,24 nmol/L:, bir yıl ve üzeri süredir takip edilen hastalarda 10,68 nmol/L, kontrol grubunda 1,44 nmol/L , p <0,05,).
Sonuç: Serum ve diğer vücut sıvılarında NPT seviyelerinin izlenmesi, otoimmün hastalıkların tanısını, prognozunu ve tedavi etkinliğini değerlendirmede kullanılabilir. Ayrıca NPT, Graves hastalığının tanısının yanı sıra hastalık evresini, tedavi etkinliğini ve immünolojik remisyon durumunu belirlemek için potansiyel bir biyobelirteç olarak öne sürülebilir.

Anahtar Kelimeler

Neopterin, Graves hastalığı, Hipertiroidizm, Hücresel bağışıklık, Yardımcı T hücreleri.

Kaynakça

• Kahaly GJ, Bartalena L, Hegedüs L, Leenhardt L, Poppe K, Pearce SH. 2018 European Thyroid Association Guideline for the management of Graves’ hyperthyroidism. Eur Thyroid J. 2018;7(4):167-186.
• Taylor PN, Albrech D, Scholz A, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. 2018;14(5):301-316.
• Sjölin G, Holmberg M, Törring O, et al. The long-term outcome of treatment for Graves’ hyperthyroidism. Thyroid. 2019;29(11):1545-1557.
• Li Q, Wang B, Mu K, Zhang JA. The pathogenesis of thyroid autoimmune diseases: new T lymphocytes-cytokines circuits beyond the Th1-Th2 paradigm. J Cell Physiol. 2019;234(3):2204-2216.
• Nanba T, Watanabe M, Inoue N, Iwatan 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(5):495-501.
• Horiya M, Anno T, Kawasaki F, et al. Basedow’s disease with associated features of Hashimoto’s thyroiditis based on histopathological findings. BMC Endocr Disord. 2020;20(1):120.
• Ekin S, Sivrikaya A, Akdağ T, Yilmaz S, Gülcemal S. Elevated levels of neopterin and pentraxin 3 in patients with rheumatoid arthritis. Horm Mol Biol Clin Investig. 2021;42(4):419-423.
• Gürcü S, Girgin G, Yorulmaz G, Kılıçarslan B, Efe B, Baydar T. Neopterin and biopterin levels and tryptophan degradation in patients with diabetes. Sci Rep. 2020;10(1):1-8.
• Wagner R, Hayatghebi S, Rosenkranz M, Reinwein D. Increased serum neopterin levels in patients with Graves’ disease. Exp Clin Endocrinol. 1993;101(4):249-254.
• Sjölin G, Watt T, Byström K, et al. Long term outcome after toxic nodular goitre. Thyroid Res. 2022;15(1):20.
• Sahin Tekin M, Kocaturk E, Gurcu S, Kayadibi H, Dibeklioglu B, Yorulmaz G. Cellular immunity in subacute thyroiditis: a new perspective through neopterin. Clin Exp Immunol. 2022;209(1):109-114.
• Krause A, Protz H, Goebel K. Correlation between synovial neopterin and inflammatory activity in rheumatoid arthritis. Ann Rheum Dis. 1989;48(8):636-640.
• Hagihara M, Nagats T, Ohhashi M, Miura T. Concentrations of neopterin andbiopterin in serum from patients with rheumatoid arthritis or systemiclupus erythematosus and in synoviai fluid from patients with rheumatoid orosteoarthritis. Clin Chem. 1990;36(4):705-706.
• Arshadi D, Nikbin B, Shakiba Y, Kiani A, Jamshidi AR, Boroushaki MT. Plasma level of neopterin as a marker of disease activity in treated rheumatoid arthritis patients: association with gender, disease activity and anti-CCP antibody. Int Immunopharmacol. 2013;17(3):763-767.
• Schroecksnadel K, Frick B, Kaser S, et al. Moderate hyperhomocysteinaemia and immune activation in patients with rheumatoid arthritis. Clinica Chimica Acta. 2003;338(1-2):157-164.
• Beckham JC, Caldwell DS, Peterson BL, et al. Disease severity in rheumatoid arthritis: relationships of plasma tumor necrosis factor-α, soluble interleukin 2-receptor, soluble CD4/CD8 ratio, neopterin, and fibrin D-dimer to traditional severity and functional measures. J Clin Immunol. 1992;12(5):353-361.
• Hanafusa T, Pujol-Borrell R, Chiovato L, Russell RC, Doniach D, Bottazzo GF. Aberrant expression of HLA-DR antigen on thyrocytes in Graves’ disease: relevance for autoimmunity. Lancet. 1983;2(8359):1111-1115.
• Schomburg A, Grünwald F, Schultes B, Hotze A, Bender H, Biersack HJ. Are serum neopterin concentrations superior to other parameters in the differential diagnosis and prognostic assessment of Graves’ disease? Exp Clin Endocrinol Diabetes. 1996;104(2):123-129.
• Zantut-Wittmann DE, Tambascia MA, da Silva Trevisan MA, Pinto GA, Vassallo J. Antithyroid drugs inhibit in vivo HLA-DR expression in thyroid follicular cells in Graves’ disease. Thyroid. 2001;11(6):575-580.
• Stasiak M, Lewiński A. New aspects in the pathogenesis and management of subacute thyroiditis. Rev Endocr Metab Disord. 2021;22(4):1027-1039.