Elsevier

Immunology Letters

Volume 78, Issue 3, 1 October 2001, Pages 123-126
Immunology Letters

Serum l-selectin and ICAM-1 in patients with Graves’ ophthalmopathy during treatment with corticosteroids

https://doi.org/10.1016/S0165-2478(01)00252-8Get rights and content

Abstract

Circulating forms of l-selectin were found to be elevated in several autoimmune diseases. ICAM-1 has been suggested a predictor of the onset of GO. The aim of the study was an estimation of serum l-selectin and ICAM-1 in patients with Graves’ disease with ophthalmopathy during treatment with corticosteroids to assess their potential as a guideline of immunosuppressive therapy. We detected serum l-selectin and ICAM-1 in three groups of subjects: 20 patients with Graves’ disease without ophtamopathy (Gd), 17 patients with clinical symptoms of ophthalmopathy (CAS≥3, anamnesis of GO≥1 year) and 24 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of metyloprednisolone (MP) and subsequent treatment with oral prednisone (P). The serum samples were collected 24 h before MP, 24 h after MP, 12±2 days of treatment with prednisone and after the end of the corticosteroid therapy. The levels of soluble l-selectin and ICAM-1 in the serum were determined by the ELISA method. The statistical significance was estimated by the Mann-Whitney U-test. Serum l-selectin and ICAM-1 were significantly increased in patients with GO (respectively 1182±222 and 438±68 ng/ml) and in patients with Graves’ disease without ophthalmopathy (respectively: 1168±130 and 343±109) in relation to the controls. After MP treatment in corticosteroid-responsive patients (improvement in CAS ≤1) serum concentration of l-selectin and ICAM-1 decreased significantly and gradually increased during subsequent treatment with prednisone. In corticosteroid-responsive patients serum l-selectin was significantly higher before MP administration and after P treatment in relation to corticosteroid-resistant subjects. Conclusions: 1. Serum l-selectin and ICAM-1 were elevated in patients with active GO 2. Metyloprednizolone decreased levels of the studied adhesion molecules in corticosteroid-responsive patients with GO 3. Lack of clinical results in corticosteroid therapy in patients with a low starting l-selectin level would suggest the possibility of serum l-selectin estimation as a prognostic for immunotherapy efficacy.

Introduction

The most difficult clinical problem in the treatment of Graves’ disease is severe ophthalmopathy (GO). Some patients with progressive exophthalmos, chemosis, ophthalmoplegia or loss of vision need to be treated with immunosuppressive medications, most often by corticosteroids. However the efficacy of corticosteroids is limited and their use entails considerable risk. There have been many attempts to find reliable predictors of response to immunosuppressive treatment, both clinical, obtained by imaging methods or laboratory but very few involving the immune system [1], [2], [3], [4]. l-selectin is responsible for the initiation of leucocyte migration through the endothelium and thus, shed from the cell surface, may reflect the earliest events of cell adhesion [5]. Circulating forms of l-selectin (sl-selectin) have been found elevated in the active stage of several autoimmune diseases [6], [7]. ICAM-1 (Intercellular adhesion molecule 1) was shown to play an important role in the interaction of immunocompetent cells with fibroblasts of the retroocular tissue in patients with GO [8]. Increased serum ICAM-1 (sICAM-1) was suggested as a marker of subclinical retro orbital connective inflammation in Gd patients [9]. The aim of the study was an estimation of serum l-selectin and ICAM-1 in patients with Graves’ disease with ophthalmopathy during treatment with corticosteroids and an assessment of their potential as a guideline of immunosupressive therapy.

Section snippets

Subjects and methods

The study was carried out in three groups of subjects: 1/17 patients with clinical symptoms of ophthalmopathy (GO)(12 females and five males, mean age 42.2±16.5 years). All the individuals in this group presented a Clinical Activity Score of eye changes (CAS)≥3 [1] and anamnesis of GO≤1 year. All of them underwent corticosteroid therapy consisting of intravenous infusions of methyloprednisolone (MP) (two series, 3 g each time) and subsequent treatment with oral prednisone (P) (60 mg per day for

Results

The results of serum l-selectin and sICAM-1 level determination are shown in Table 1. We found a significantly higher serum l-selectin level both in Gd and GO patients in comparison to the control group (P<0.05). Serum ICAM-1 levels were significantly higher both in Gd and GO individuals in relation to the controls (respectively P<0.01 and 0.001).

The serum l-selectin and sICAM-1 levels during corticosteroid treatment in GO patients are shown in Table 2. There were significant differences in

Discussion

For many years corticosteroids have been accepted as the treatment of choice in the Graves ophthalmopathy however their administration is limited by several problems: an inability to predict which patients will respond, lack of a satisfactory understanding of their mechanism of action and no guidelines of treatment so as to maximize benefits and minimize complications. There are no established predictors of response to immunosuppressive treatment involving the immune system. Some adhesion

Conclusion

Serum l-selectin and ICAM-1 were elevated in patients with active GO 2. Metyloprednizolone decreased levels of the studied adhesion molecules in corticosteroid-responsive patients with GO 3. Lack of clinical results in corticosteroid therapy in patients with a low starting l-selectin level would suggest the possibility of serum l-selectin estimation as a prognostic for immunotherapy efficacy.

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