Association between clinical activity score and serum sPD-1 and sPD-L1 levels during systemic glucocorticoid treatment for active moderate-to-severe thyroid eye disease.

BACKGROUND

CD4+ T lymphocytes are key immune cells involved in orbital inflammation in thyroid eye disease (TED). Inhibition of their activity is important in treatment of TED, but effective drugs targeting these cells are lacking. The programmed cell death-1/programmed cell death ligand-1 pathway has been implicated in several T-cell-mediated diseases. Manipulation of this pathway with antagonists or agonists is an attractive therapeutic option. The role of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) in regulation of this pathway is debated. This study aimed to investigate the involvement of sPD-1 and sPD-L1 in the pathogenesis of TED, focusing on their utility as novel biomarkers to evaluate disease severity and treatment response.

METHODS

Thirty patients diagnosed with moderate-to-severe TED associated with Graves' disease were included. Blood samples were collected from patients before and 12 weeks after initiation of intravenous glucocorticosteroid (IVGC) treatment. Disease severity was assessed using the Clinical Activity Score (CAS) before and after IVGC treatment. Thyroid-stimulating hormone, free thyroxine, free triiodothyronine, thyroid-stimulating immunoglobulin, interleukin-6, sPD-1, and sPD-L1 levels were measured. Correlations between sPD-1, sPD-L1, and CAS before and after IVGC treatment were investigated. Serum concentrations of sPD-1 and sPD-L1 before and after IVGC treatment in patients with TED were compared with those in healthy controls (HCs). The changes in the tested protein concentrations upon IVGC treatment and their associations with clinical characteristics were investigated. Enzyme-linked immunosorbent assays were used to measure sPD-1 and sPD-L1 concentrations in peripheral blood serum.

RESULTS

There was a positive correlation of moderate Spearman's rank strength between sPD-L1 and CAS before and after treatment, and a positive correlation between sPD-1 and sPD-L1. 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 HCs. There were no correlations between changes in the levels of the tested molecules upon IVGC treatment and the analyzed clinical features. The decreases of sPD-1 and sPD-L1 levels after 12 weeks of IVGC treatment were not significant.

CONCLUSION

The positive correlation of moderate Spearman's rank strength between sPD-L1 and CAS before and after 12 weeks of treatment indicates that sPD-L1 is involved in the pathogenesis of TED. sPD-L1 may become an additional immunological biomarker to assess the disease activity and monitor the respond to treatment. Although sPD-1 is reported in the literature to have an activating effect on lymphocytes, our study shows that sPD-1 may not play a significant role in the pathogenesis of TED, as its level does not differ significantly between the TED and HC groups and does not correlate with disease activity. Understanding the clinical value of sPD-1 and sPD-L1 is of great practical importance.