Protein spectrum changes in exosomes after therapeutic plasma exchange in patients with neuromyelitis optica.

Abstract

Neuromyelitis optica (NMO) is an autoimmune disease with a high rate of blindness and positive for the detection of aquaporin-4 antibody (AQP4) in most patients. NMO acute attacks are managed by high-doses of intravenous methylprednisolone followed by oral taper, and if symptoms fail to resolve, therapeutic plasma exchange (TPE) is added. TPE can remove pathological antibodies and inflammatory factors leading to clinical improvement. A total of 40 TPE fluid collections from the first to fifth TPE treatments were obtained from eight patients. Exosomes were isolated by ultracentrifugation. Mass spectrometry analyses were used to compare protein change in TPE fluid collection exosomes after the first to the fifth TPE treatments in these patients. We detected 647 exosome proteins through data-independent acquisition analysis. It was found that some unknown functional antibody fragments and complement pathway proteins decreased after TPE treatment. The results revealed a significant involvement of the following two key pathways: the primary immunodeficiency and systemic lupus erythematosus that may be associated with NMO pathophysiology and TPE treatment efficacy (P < .05). A series of complement proteins may contribute to NMO; in addition, the following proteins increased with plasma exchange: complement factor H-related protein 5, bridging integrator 2, neuroplastin, pigment epithelium-derived factor, ficolin-1, extracellular matrix protein 1, and fatty acid-binding protein 5. Our study may provide a new perspective on the pathogenesis and treatment efficacy of NMO.