Establishment of a tear protein biomarker panel differentiating between Graves' disease with or without orbitopathy.

Cecilie Aass,Milaim Pepaj,Erik Fink Eriksen,Ingrid Norheim,Ellen Charlotte Børnick,Per Medbøe Thorsby,Paula Soares

doi:10.1371/journal.pone.0175274

Cecilie Aass, Milaim Pepaj + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0175274

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Journal: PloS one	Publication Date: Apr 18, 2017
Citations: 14	License type: CC BY 4.0

Affiliation: Oslo University Hospital, University of Oslo

Abstract

BackgroundGraves’ orbitopathy (GO) is an autoimmune inflammatory ocular complication and one of the most frequent manifestations of Graves’ disease (GD). Clinical judgment of GO is subjective sometimes leading to clinical and therapeutic challenges. Better tools to diagnose this severe complication are warranted.Patients and methodsThe aim of the present study was to evaluate tear levels of LYZ, LACRT and AZGP1 in GD patients with or without GO, as possible biomarkers for GO. Tear samples were collected from GD patients with moderate-to-severe GO (n = 21) and no clinical signs of GO (n = 21). Additionally, 18 GD patients with mild GO and 9 patients without GO were included in a further part of the study.ResultsTear levels of LYZ (p < 0.001), LACRT (p = 0.004) and AZGP1 (p = 0.001) were significantly elevated in GD patients with moderate-to-severe GO compared to GD patients without GO. The discriminatory power of the three biomarkers, combined in a panel was confirmed by ROC plot analysis, with an AUC value of 0.93 (sensitivity of 95%; specificity of 80%). Since LYZ showed the best performance in discriminating between GD patients with (moderate-to-severe) and without GO (in combination with limited sample volume available), LYZ levels were also measured in tears from GD patients with mild GO and without GO. Significantly higher levels of LYZ were measured in GD patients with mild GO compared to those without GO (p = 0.003).ConclusionsWe have established a novel three-protein biomarker panel that is able to discriminate between GD patients with and without GO, which might aid in diagnostic evaluation of GO as well as an indicator for disease activity.

Highlights

Graves’ orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and one of the most frequent manifestations of Graves’ disease (GD) [1, 2]
Since lysozyme C (LYZ) showed the best performance in discriminating between GD patients with and without GO, LYZ levels were measured in tears from GD patients with mild GO and without GO
We have established a novel three-protein biomarker panel that is able to discriminate between GD patients with and without GO, which might aid in diagnostic evaluation of GO as well as an indicator for disease activity

Summary

Introduction

Graves’ orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and one of the most frequent manifestations of Graves’ disease (GD) [1, 2]. GO is clinically apparent in approximately 20% of patients with GD [4, 6], and is characterized by inflammatory changes and enlargement of extraocular muscles and orbital tissues These changes, combined with the local production of cytokines and other mediators of inflammation, result in upper eyelid retraction, edema, proptosis, diplopia, erythema of the perorbital tissues and conjunctivae, and even sight loss due to compressive optic neuropathy or breakdown of cornea [7, 8]. Graves’ orbitopathy (GO) is an autoimmune inflammatory ocular complication and one of the most frequent manifestations of Graves’ disease (GD).

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