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Published on: August 21, 2017
Different Complement Activation Patterns Following C5 Cleavage in MOGAD and AQP4-IgG+NMOSD
Kimihiko Kaneko1, Hiroshi Kuroda1, Yuki Matsumoto1
1From the Department of Neurology (K.K., H.K., Y.M., N.S., N. Yamazaki, N. Yamamoto, S.U., C.N., H.O., Y.T., T.T., K.F., T.M., M.A.), Tohoku University Graduate School of Medicine, Sendai, Japan; Multiple Sclerosis and Neuromyelitis Optica Center (H.K., K.F.), Southern TOHOKU Research Institute for Neuroscience, Koriyama; Department of Multiple Sclerosis Therapeutics (H.K., K.F.), Fukushima Medical University, Fukushima, Japan; Department of Neurology (T.T.), NHO Yonezawa National Hospital, Yamagata, Japan; Division of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai, Japan; Department of Neurology (Y.H.), Japanese Redcross Maebashi Hospital; Department of Neurology (Y.H.), Mihara Memorial Hospital, Isesaki, Japan; and Center for Brain Research (H.L.), Medical University of Vienna, Austria.
Complement activation occurs in both MOGAD and AQP4+NMOSD. However, membrane attack complex formation is reduced in MOGAD, especially in milder cases, suggesting potential therapeutic targets.
Area of Science:
- Neuroimmunology
- Complement System Biology
- Autoimmune Neurology
Background:
- Myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD) are autoimmune conditions where IgG1 antibodies play a role.
- Complement-dependent cytotoxicity is a key mechanism in AQP4+NMOSD pathogenesis.
Purpose of the Study:
- To investigate and compare cerebrospinal fluid (CSF) complement activation patterns in patients with MOGAD and AQP4+NMOSD.
- To explore the relationship between complement activation and disease severity in MOGAD.
Main Methods:
- Measurement of CSF complement components (C3a, C4a, C5a, and C5b-9/MAC) during the acute phase before treatment.
- Comparison of complement levels in patients with MOGAD (n=12), AQP4+NMOSD (n=11), multiple sclerosis (MS, n=5), and noninflammatory neurologic disease (n=2).
Main Results:
- CSF C3a and C5a levels were elevated in both MOGAD and AQP4+NMOSD compared to MS.
- While CSF C3a, C4a, and C5a did not differ between MOGAD and AQP4+NMOSD, CSF C5b-9 (MAC) levels were significantly lower in MOGAD.
- Higher C5b-9 levels in MOGAD correlated with more severe attacks (EDSS ≥ 3.5).
Conclusions:
- The complement pathway is activated in both MOGAD and AQP4+NMOSD.
- Membrane attack complex (MAC) formation is less pronounced in MOGAD compared to AQP4+NMOSD, particularly in patients with milder disease.
- These findings highlight potential differences in complement pathway utilization and offer insights for MOGAD pathogenesis and treatment strategies.
