PD-L1-expressing neutrophils as a novel indicator to assess disease activity and severity of systemic lupus erythematosus

Abstract

Background: It is well-known that increased frequency of neutrophils was found in patients with systemic lupus erythematosus (SLE). However, the immunomodulatory roles and mechanisms of neutrophils in SLE are poorly understood. Methods: Patients with SLE were recruited from the First Affiliated Hospital of Nanchang University. The medical history, clinical manifestations, physical examination, laboratory measurements, therapeutic regimen and treatment response were recorded. The expression of costimulatory molecules including programmed death 1 (PD-1), programmed death ligand 1 (PD-L1), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), CD40, T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains (TIGIT), CD80 and CD86 on neutrophils were determined by flow cytometry. The frequencies of PD-L1-expressing neutrophils in patients with SLE were further analyzed for their correlation with markers of autoimmune response, inflammation, disease activity and severity of SLE. Results: The frequency of PD-L1-expressing neutrophils was significantly elevated in SLE patients compared to the healthy controls (P < 0.0001). The frequency of PD-L1-expressing neutrophils in patients with SLE was increased significantly in subjects with high ANA titre, high anti-nRNP/Sm, high levels of inflammatory markers and high SLE Disease Activity Index (SLEDAI) score. Furthermore, the percentages of PD-L1-expressing neutrophils were significantly decreased in SLE patients that received a 15-day regular treatment with corticosteroids and immunosuppressive drugs (P = 0.0075). Conclusion: The frequency of PD-L1-expressing neutrophils is elevates in patients with SLE, correlates with the disease activity and severity of SLE, and may serves as a negative feedback mechanism preventing potential tissue damage caused by excessive autoimmune responses in patients with SLE.