Abstract

The aim of the study was to evaluate the distribution of blood dendritic cells (DCs) in patients with Graves' orbitopathy (GO) and to assess the influence of methylprednisolone therapy on subsets of peripheral blood mononuclear cells (PBMCs). Peripheral blood DC subsets were analyzed by flow cytometry in patients with active GO (n = 17), inactive GO (n = 8), and Graves' disease (GD) without GO (n = 8) and controls (n = 15); additionally, in patients with active GO (n = 17), analyses were done at three time points, i.e., before methylprednisolone treatment and after 6 weeks and after 12 weeks of the treatment. Percentage of myeloid DCs (mDCs) in PBMC fraction was significantly lower in patients with both active and inactive GO, compared to patients with GD without GO and controls (p < 0.05). In addition, mDCs were also documented to be an independent factor negatively associated with GO, however without essential differences between active and inactive phases. On the other hand, we did not observe any changes in the percentage of DCs after methylprednisolone therapy (p > 0.05). In the present study, we have succeeded to firstly demonstrate—according to our knowledge—that blood mDCs are negatively related to GO incidence.

Highlights

  • Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD)

  • The quantitative flow cytometric analysis showed that the percentage of myeloid DCs (mDCs) (CD141) in whole peripheral blood mononuclear cells (PBMCs) fraction is significantly lower in GO in comparison to GD without GO and controls, without differences observed between the latter two groups (p < 0:05) (Figure 2)

  • The percentage of pDCs (CD303) is significantly lower in GO when compared to controls (p < 0:05), but it is not proven to be lower in comparison to GD patients without GO (p > 0:05); at the same time, no statistical differences were found between GD

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Summary

Introduction

Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). It has a selflimited active phase, followed by an inactive phase. Orbitopathy remains a difficult clinical problem, and treatment options of severe active disease have been limited to steroids in the majority of cases [1]. The lack of development of specific medical therapies for GO results—in large part—from poor understanding of disease pathogenesis. While major breakthroughs continue to occur in closely related thyroid autoimmune diseases, a progress in identifying the pathogenic mechanisms relevant to GO is not satisfactory. The breakdown of central and peripheral immune tolerance to autoantigens in autoimmune diseases, including GO, is largely due to deficient immune regulation

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