Endocrine Abstracts

JOINT1561

Introduction: T cell activation plays a crucial role in the pathogenesis of thyroid eye disease (TED). The programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway, as an immune checkpoint, regulates T cells responses, including to self-antigens. PD-L1, primarily expressed on antigen-presenting cells during inflammation, binds to PD-1 on B and T cells. Soluble forms of these molecules (sPD-L1 and sPD-1) maintain the ability to bind to membrane counterparts. As their interaction affects immune tolerance, regulation of this pathway is an attractive therapeutic option. However, there are limited data on the relevance of sPD-1 and sPD-L1 in TED. The aim of this study is to assess the role of sPD-1 and sPD-L1 in the pathogenesis of TED and to evaluate their potential as biomarkers to improve disease diagnosis and the assessment of disease activity.

Methodology: This is a single-center, prospective study on patients diagnosed with moderate-to-severe TED associated with Graves’ disease, who were qualified for intravenous corticosteroid treatment (IVGC) according to the European Group on Graves’ Orbitopathy (EUGOGO) guidelines. Blood samples were collected from patients before and 12 weeks after starting IVGC treatment. Levels of thyrotropic hormone (TSH), free thyroxine, free triiodothyronine, thyroid-stimulating immunoglobulin, TSH receptor antibodies, and interleukin-6 were measured using immunoassays. Enzyme-linked immunosorbent assays (ELISA) were used to measure sPD-1 and sPD-L1 concentrations in peripheral blood serum. Disease activity was assessed using the Clinical Activity Score (CAS). Correlations between the studied molecules and CAS before and after IVGC treatment were investigated. Concentrations of sPD-1 and sPD-L1 were compared with those of healthy controls (HC).

Results: Thirty patients were enrolled. Statistical analysis revealed a positive correlation between sPD-L1 and CAS before (rho = 0.42, P = 0.0194) and after (rho = 0.37, P = 0.0412) 12 weeks of IVGC treatment. sPD-1 also positively correlated with sPD-L1 before (rho = 0.93, P < 0.0001) and after (rho = 0.88, P < 0.0001) treatment. However, no correlation was observed between sPD-1 and CAS. Baseline serum levels of sPD-1 and sPD-L1 did not significantly differ between patients with TED and HC. The decreases in sPD-1 and sPD-L1 levels after 12 weeks of IVGC treatment were not significant.

Conclusion: Our results showed that sPD-L1 levels may serve as a novel immunological marker for disease activity and the monitoring of treatment response in patients with TED. However, sPD-1 may not play a significant role in the pathogenesis of TED.