Plasma complement 3 (C3) and complement 4 (C4) are promising biomarkers for distinguishing neuromyelitis optica spectrum disorder (NMOSD) from myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), with C3 and C4 linked to blood-brain-barrier (BBB) disruption in individuals with NMOSD.

A single-center, retrospective, observational study was conducted among patients recruited from the affiliated brain hospital of Nanjing Medical University in China between 2012 and 2021. Results of the analysis were published in the journal Frontiers in Immunology.

The investigators sought to establish whether C3 or C4 has an impact on the features of patients with NMOSD, in an attempt to differentiate NMOSD from MOGAD. They explored whether plasma levels of C3 and C4 differ during acute attacks of both diseases.

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It is well known that NMOSD and MOGAD are both autoimmune inflammatory demyelinating diseases of the central nervous system (CNS). In patients with NMOSD, the optic nerves and spinal cord are primary target sites, with the antibody target for the water channel aquaporin-4 (AQP4) a pathogenic marker of this disorder.

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In the current study, data from 73 AQP4 immunoglobulin (IgG)–positive patients with NMOSD and 22 MOG-IgG–positive patients with MOGAD were obtained retrospectively. IgG and albumin levels were measured in both plasma and CSF. Further, plasma levels of C3 and C4 were compared among the NMOSD group, the MOGAD group, and 42 healthy controls.

Results of the study showed a significant female gender predominance among those in the NMOSD arm compared with the MOGAD arm (94.52% vs 27.27%, respectively; P <.001). Although the age at onset was slightly higher in the NMOSD group than in the MOGAD group, the difference was not statistically significant.

Significant differences were observed between the NMOSD and MOGAD arms with respect to optic neuritis (57.53% vs 31.82, respectively; P =.034) and transverse myelitis (75.34% vs 31.82%, respectively; P <.001)—both of which were more common among those with NMOSD. In contrast, acute disseminated encephalomyelitis was significantly more common among those with MOGAD than those with NMOSD (50% vs 9.59%, respectively; P <.001).

Plasma levels of IgG in patients with MOGAD were significantly lower than in those with NMOSD
(P =.027), whereas plasma levels of albumin were significantly higher in patients with MOGAD vs those with NMOSD (P =.039). Further, both plasma C3 and C4 levels were significantly lower in the NMOSD arm than in the MOGAD arm and in the healthy controls.

According to the researchers, “During the acute phase of NMOSD and MOGAD, plasma C3 and C4 may become potential biomarkers for distinguishing the two diseases and reflecting the NMOSD BBB damage.”


Lin L, Wu Y, Hang H, Lu J, Ding Y. Plasma complement 3 and complement 4 are promising biomarkers for distinguishing NMOSD from MOGAD and are associated with the blood-brain barrier disruption in NMOSD. Front Immunol. Published online July 11, 2022. doi:10.3389/fimmu.2022.853891