Increased Levels of Soluble Programmed Death Ligand 1 Associate with Malignancy in Patients with Dermatomyositis

Abstract

Objective: To investigate the levels of soluble programmed death ligand 1 (sPD-L1) and evaluate its association with malignancy in patients with dermatomyositis (DM).

Methods: Levels of sPD-L1 were measured in serum from 88 DM patients without malignancies (sDM), 40 with cancer-related DM (CRDM), and 30 healthy controls (HC) using ELISA. The CRDM subjects were divided into new-onset cancers (nCRDM) and stable cancers (sCRDM). Receiver-operating characteristic (ROC) curve analysis was performed to determine the cutoff sPD-L1 value that distinguished patients with nCRDM from those who were sDM. Serum antitranscriptional intermediary factor 1-γ (TIF1-γ) antibodies were detected using immunoblot, and the diagnostic values for malignancy were compared with sPD-L1 levels in patients with DM.

Results: Serum sPD-L1 levels were significantly higher in sDM [median 12.3 ng/ml, interquartile range (IQR) 8.4-16.2] than in HC (median 1.3 ng/ml, IQR 0.4-2.2, p = 0.0001). Extremely high sPD-L1 levels were seen in nCRDM (median 18.5 ng/ml, IQR 13.8-22.4), much higher than those in sCRDM (median 8.5 ng/ml, IQR 6.8-11.8, p = 0.0001). The sPD-L1 levels in 4 patients with nCRDM decreased after curative cancer treatment (p = 0.013). ROC curve analysis revealed that the sPD-L1 value distinguishing nCRDM from sDM was 16.1 ng/ml, with an area under the curve value of 0.72 ± 0.04 (p = 0.0001). The combination of sPD-L1 and anti-TIF1-γ antibodies yielded greater specificity and positive predictive value in diagnosing cancer, reaching values of 95% and 70%, respectively.

Conclusion: Serum sPD-L1 levels increased significantly in sDM, and markedly high sPD-L1 levels could be a diagnostic indicator for malignancies in patients with DM, especially in those with anti-TIF1-γ antibodies.

Keywords: BIOLOGICAL MARKERS; DERMATOMYOSITIS; MALIGNANCY; PROGRAMMED DEATH LIGAND 1.