Clinical value of thyrotropin receptor antibodies in patients with Gravesʹ orbitopathy/ophthalmopathy

[M. J. Sarić Matutinović]

231 str.

Medicinske nauke - Farmacija - Medicinska biohemija / Medical sciences - Pharmacy - Medical biochemistry

Graves-ova orbitopatija (GO) je multifaktorska autoimuna bolest, još uvek nepotpuno istražene etiologije i patogeneze. Osnovu ove patologije čini inflamatorni poremećaj orbite. Obično se javlja u sklopu autoimunih bolesti tiroidne žlezde (AITB), prvenstveno Graves-ove bolesti (GB), međutim poznati su slučajevi njene izolovane pojave u odsustvu tiroidnih abnormalnosti. Graves-ova orbitopatija značajno remeti svakodnevne aktivnosti, funkciju vida i fizički izgled pacijenata, a u najtežim slučajevima može dovesti do potpunog gubitka vida. Smatra se da su autoreaktivna antitela na TSH receptore (TSHRAt) prisutna u orbiti i štitnoj žlezdi glavni uzročnici nastanka GO i GB. Glavni cilj ovog istraživanja bio je ispitivanje kliničkog značaja ovih autoreaktivnih antitela u dijagnostici GO, klasifikaciji pacijenata, predviđanju kliničkog toka i ishoda ove bolesti. Sa tim u vezi, analizirane su: raspodela ukupne koncentracije i funkcionalnog profila TSHRAt u različitim grupama pacijenata, njihova asocijacija sa kliničkom slikom bolesti i dijagnostičke karakteristike primenjenih analitičkih metoda za njihovo određivanje. Dodatni cilj je bio analiza citokinskog profila i oksidativnog statusa pacijenata, kao i njihovog međusobnog odnosa sa nivoima TSHRAt. U studiji je učestovao 91 pacijent sa postavljenom dijagnozom GO koji nije primao imunosupresivnu terapiju minimalno šest meseci u odnosu na datum uključenja u studiju. Pacijenti su lečeni na Klinici za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetskog kliničkog centra Srbije, a klasifikovani su u odnosu na vrstu primarne dijagnoze na: pacijente sa GB, Hašimoto tiroiditisom (HT) i na pacijente bez tiroidne disfunkcije (eutiroidna GO, ET GO). Osim toga, klasifikacija pacijenata je izvršena i prema kliničkim karakteristikama GO, pre svega prema aktivnosti i težini. Ukupna koncentracija TSHRAt (TSH vezujući inhibitorni imunoglobulini, TBII) određena je primenom komercijalne rutinske imunohemijske metode. Stimulatorna (TSHR-stimulatorna antitela, TSAb) i blokirajuća aktivnost antitela (TSHR-blokirajuća antitela, TBAb) određene su tehnikom bioeseja. Zasebno su kvantifikovana stimulatorna i blokirajuća antitela. Dodatno je koncentracija TSHRAt izmerena pomoću komercijalne imunohemijske metode koja koristi „sendvič“ princip. Ispitivani citokini i 8-hidroksi-2-deoksigvanozin (8-OhdG) su određeni komercijalnim enzimskim imunohemijskim testovima, dok su totalni oksidativni stres (TOS) i totalni antioksidantni status (TAS) određeni spektrofotometrijski, primenom komercijalnih testova...

Graves' orbitopathy (GO) is a multifactorial autoimmune disease of insufficiently investigated etiology and pathogenesis. The basis of this pathology is characterized by an inflammatory disorder of the orbit. It is mostly occurring in patients with autoimmune thyroid diseases (AITD), primarily Graves' disease (GD). However, there are known cases of its isolated occurrence in the absence of thyroid abnormalities. Graves' orbitopathy seriously impairs patients’ daily activities, vision function and physical appearance, and in severe cases may cause blindness. Autoreactive antibodies to TSH receptors (TSHRAb) present in the orbit and thyroid are considered the main causes of both GO and GD. The primary goal of this study was to examine the clinical significance of these autoantibodies in the diagnosis of GO, patient classification, prediction of the clinical course and outcome of this disease. In this regard, we analyzed the distribution of the total TSHRAb concentration and functional profile in different patient groups, along with their association with the clinical profile of the disease and diagnostic accuracy of the applied analytical methods for their determination. An additional goal was to analyze the cytokine profile and oxidative status of patients, as well as their relationship with TSHRAb levels. Ninety-one patients diagnosed with GO were enrolled in this study. They had not received any form of immunosuppressive therapy for at least six months prior the recruitment. All patients were on a regular follow-up regimen at the Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Medical Center of Serbia, and were classified according to their primary diagnosis into: patients with GD, Hashimoto's thyroiditis (HT) and patients without thyroid dysfunction (euthyroid GO, ET GO). Additionally, patients were classified according to the clinical characteristics, primarily activity and severity of GO. Total TSHRAb concentration (TSH binding inhibitory immunoglobulins, TBII) was measured using a commercial routine immunoassay. Stimulatory and blocking antibody activity (TSHR-stimulating antibodies, TSAb and TSHR-blocking antibodies, TBAb, respectively) were determined using a bioassay technique. Stimulatory and blocking antibodies were separately quantified. In addition, TSHRAb concentration was measured using a commercial "bridge" immunoassay...

Graves-ova orbitopatija; Graves-ova bolest; TSH-receptorska antitela; funkcionalna aktivnost TSH-receptorskih antitela; tehnika bioeseja

Graves' orbitopathy; Graves' disease; TSH-receptor antibodies; functional activity of TSH-receptor antibodies; bioassay technique

615:616.441-008.61-07(043.3)

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