Association of plasma sPD‐1 and sPD‐L1 with disease status and future relapse in AQP4‐IgG (+) NMOSD

Abstract Objective Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune‐mediated disorder with aquaporin 4‐immunoglobulin G (AQP4‐IgG) in most settings. Soluble programmed death‐1 (sPD‐1) and soluble programmed death ligand 1 (sPD‐L1) play key roles in immunomodulation. We aim to assess the association of sPD‐1 and sPD‐L1 with cytokines and their clinical significance in AQP4‐IgG (+) NMOSD. Method We measured plasma sPD‐1, sPD‐L1, and 10 cytokines levels of 66 AQP4‐IgG (+) NMOSD patients, including 40 patients in attack (attack‐NMOSD) and 26 patients in remission (remission‐NMOSD) phases, and 28 healthy controls through ultrasensitive Simoa and SP‐X platform, respectively. We also performed >2 years (median) of follow‐up after testing and analyzed the relationship between the detection index and current and future clinical parameters. Result Plasma sPD‐1 level discriminated attack‐NMOSD from remission‐NMOSD (AUC = 0.692, p = 0.009). sPD‐1 and sPD‐L1 levels positively correlated with IL‐6 ( r sPD‐1 = 0.313; r sPD‐L1 = 0.508), IFN‐γ ( r sPD‐1 = 0.331; r sPD‐L1 = 0.456), and TNF‐α ( r sPD‐1 = 0.451; r sPD‐L1 = 0.531) expression, as well as clinical indicators, including the EDSS score ( r sPD‐1 = 0.331; r sPD‐L1 = 0.402), number of attacks ( r sPD‐1 = 0.431) and segments of spinal cord involvement ( r sPD‐1 = 0.462; r sPD‐L1 = 0.508). The risk of relapse within 2 years after sampling was associated with higher sPD‐1/sPD‐L1 ratio in attack‐NMOSD ( p = 0.022; Exp(B) = 1.589). Interpretation Plasma sPD‐1 and sPD‐L1 levels reflected current disease severity and activity, and predicted future relapses in AQP4‐IgG (+) NMOSD, suggesting that they hold the potential to guide timely and targeted treatment.