Abstract

The aim was to investigate the levels of cytokines and soluble IL-6R in the tears of patients with thyroid-associated orbitopathy (TAO) disease. Schirmer’s test was adopted to collect tears from TAO patients (N = 20, 17 women, mean age (±SD): 46.0 years (±13.4)) and healthy subjects (N = 18, 10 women, 45.4 years (±18.7)). Lacrimal cytokines and soluble IL-6R (sIL-6R) were measured using a 10-plex panel (Meso Scale Discovery Company) and Invitrogen Human sIL-6R Elisa kit, respectively. Tear levels of IL-10, IL-12p70, IL-13, IL-6 and TNF-α appeared significantly higher in TAO patients than in healthy subjects. Interestingly, IL-10, IL-12p70 and IL-8 levels increased in tears whatever the form of TAO whereas IL-13, IL-6 and TNF-α levels were significantly elevated in inflammatory TAO patients, meaning with a clinical score activity (CAS) ≥ 3, compared to controls. Furthermore, only 3 cytokines were strongly positively correlated with CAS (IL-13 Spearman coeff. r: 0.703, p = 0.0005; IL-6 r: 0.553, p = 0.011; IL-8 r: 0.618, p = 0.004, respectively). Finally, tobacco use disturbed the levels of several cytokines, especially in patient suffering of TAO. The differential profile of lacrimal cytokines could be useful for the diagnosis of TAO patients. Nevertheless, the tobacco use of these patients should be taken into account in the interpretation of the cytokine levels.

Highlights

  • Thyroid-associated orbitopathy (TAO) is an autoimmune disorder, very often related to Graves’ disease

  • No significant difference was observed between age and gender of these 2 groups. 14 out of 20 TAO patients had a more active form of the disease. 9 TAO patients were active tobacco consumers at the time of the tear collection apart from one person, who stopped a couple of weeks before, but was still considered as a smoker

  • The lacrimal concentration of 10 cytokines and sIL6-R in TAO patients and control subjects are shown in Fig. 1

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Summary

Introduction

Thyroid-associated orbitopathy (TAO) is an autoimmune disorder, very often related to Graves’ disease. The diagnosis of Graves’ disease is based on the detection of circulating auto-antibodies against thyroid stimulating hormone receptor (TSHR) in patient’s blood. The target cells seem to be the fibroblasts presenting the thyroid stimulating hormone receptor (TSHR)[6,7,8,9]. They display surface receptors for cytokines what render them as potential target for the immune system. Several cytokines have been shown to be present in serum[10,11,12,13,14], in orbital fat and muscles[15,16,17], and tears[18,19] of patients suffering from TAO. Cytokines could be used as potential biomarkers since they are identified as major actors in the TAO disease

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