Clinical value of plasma C1q, C3, and C4 in NMOSD and MOGAD
Yuqing Wu1, Hao Zhuo2, Xianpeng Zhang1
1The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine),310000, Hangzhou, China.
Background:
Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are both rare central nervous system autoimmune diseases. It has been reported that the pathogenicity of the complement system differs in NMOSD and MOGAD. Therefore, we aimed to analyze whether major complement plasma levels differ between patients with NMOSD and MOGAD and how they correlate with disease characteristics.
Methods:
This retrospective study included 33 patients with MOGAD and 62 with NMOSD, alongside 49 age- and sex-matched healthy controls (HC). Demographic, clinical, plasma, and cerebrospinal fluid (CSF) parameters were compared. We quantified immunoglobulin G (IgG) and albumin levels in plasma and CSF and assessed plasma complement factors (C1q, C3, C4) across all groups. Correlations between plasma complement levels and clinical parameters were specifically analyzed in the patient groups.
Results:
Compared to MOGAD patients, those with NMOSD showed a higher female predominance and a greater annual relapse rate. Myelitis was the most common clinical presentation in NMOSD, while encephalopathy was more frequent in MOGAD. Laboratory analysis indicated lower average antibody titers in MOGAD than in NMOSD. MOGAD patients exhibited a higher CSF white cell count but a lower plasma IgG level compared to those with NMOSD. Plasma levels of C1q, C3, and C4 were significantly reduced in NMOSD relative to both MOGAD and healthy controls. ROC curve analysis demonstrated that C1q, C3, and C4 had AUC values of 0.637, 0.748, and 0.687, respectively, suggesting their utility in distinguishing MOGAD from NMOSD. Correlation analyses revealed that plasma C3 and C4 were positively correlated with CSF albumin and Q-Alb in both disorders, and plasma C1q correlated positively with EDSS scores in both groups. In contrast, a significant negative correlation between plasma C3 and the IgG index was specific to NMOSD.
Conclusion:
This study confirms that reduced plasma complement levels (C1q, C3, C4) distinguish NMOSD from MOGAD. While complement levels correlate with disability and BBB disruption in both disorders, a specific inverse correlation between C3 and the IgG index is unique to NMOSD, indicating a distinct pathophysiology.
