Abnormal membrane-bound and soluble programmed death ligand 2 (PD-L2) expression in systemic lupus erythematosus is associated with disease activity.

Programmed death ligand (PD-L) 2 and PD-L1 are the second and first ligands, respectively, for programmed cell death-1 protein (PD-1), which is one of the key factors responsible for inhibitory T cell signaling, mediating mechanisms of tolerance and providing immune homeostasis. Studies have shown that PD-1 and its ligand PD-L1 are abnormally expressed in autoimmune diseases, such as rheumatoid arthritis and autoimmune hepatitis, but its other ligand, PD-L2, has rarely been studied. This study analyzed the changes in membrane-bound PD-L2 expression in peripheral blood mononuclear cells and soluble PD-L2 (sPD-L2) levels in the serum of patients with systemic lupus erythematosus (SLE) to explore the relationship between PD-L2 expression with disease activity and related test parameters. Our results showed that membrane-bound PD-L2 expression on monocytes was significantly higher and the sPD-L2 levels were significantly lower in SLE patients than in healthy subjects. Patients with active SLE accompanied by lupus nephritis, joint pain, and clinical manifestations of oral ulcers had relatively low secretion of sPD-L2. In addition, this secretion level was significantly and positively correlated with complement components 3 and 4 (C3/C4). These results suggest that PD-L2 may be a promising biomarker associated with the pathogenesis of SLE.