Background: Neuromyelitis optica (NMO) is characterized by severe optic neuritis and longitudinally extended transverse myelitis. A serum autoantibody against aquaporin-4 (AQP4), a water channel densely expressed on astrocytes, has been detected exclusively in NMO and the high-risk syndrome. Pathologically, an extensive loss of AQP4 with perivascular depositions of activated complements (C9neo) as well as immunoglobulins is seen in NMO lesions, and infiltration of neutrophils is not uncommon in those lesions. C9neo is a major component of the membrane-attack complex (MAC) to damage cellular membrane. On the other hand, anaphylatoxins produced in the process of MAC formation, especially C5a, do not bind to cellular membrane, but have such biological functions as increasing endothelial permeability and potentiating chemotaxis of neutrophils and monocytes. Thus, those anaphylatoxins might play a crucial role in the pathogenesis of NMO, but they have not been analyzed in the disease. Objective: To examine whether anaphylatoxins (complement fragments C3a, C4a, and C5a) increase in the cerebrospinal fluid (CSF) during acute exacerbation of NMO. Methods: Using a beads-based immunosorbent assay, we measured the concentrations of C3a, C4a, and C5a in CSF, obtained from the patients with NMO in relapse (n=15), MS in relapse (n=15), and other non-inflammatory neurological diseases (OND) (n=13). Results: The CSF C5a levels in NMO (296?268 pg/ml) were significantly higher than those in OND (69.9?46.0 pg/ml). The CSF C5a levels in NMO tended higher than those in MS (169?132 pg/ml), but the difference did not reach a statistical significance. The C5a levels in MS and OND were not different. Neither the CSF C3a and C4a levels nor the serum C3a, C4a, and C5a levels showed significant differences among the three groups. Conclusions: The present study showed that C5a is increased in the CSF during acute exacerbation of NMO, and suggests that C5a is not only a secondary product in the complement activation, but may also directly contribute to the proinflammatory process in NMO lesions by disrupting the blood-brain barrier integrity and promoting neutrophilic chemotaxis.
Read More: Increase of cerebrospinal fluid anaphylatoxin C5a in neuromyelitis optica