Cho EB, Min JH, Waters P, Jeon M, Ju ES, Kim HJ, Kim SH, Shin HY, Kang SY, Lim YM, Oh SY, Lee HL, Sohn E, Lee SS, Oh J, Kim S, Huh SY, Cho JY, Seok JM, Kim BJ, and Kim BJ
Background: Myelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases., Methods: The sera of patients with MOGAD (from during an attack and remission; N =19 and N =9, respectively) and AQP4-NMOSD ( N =35 and N =17), and healthy controls ( N =38) were analyzed for C1q-binding circulating immune complex (CIC-C1q), C1 inhibitor (C1-INH), factor H (FH), C3, iC3b, and soluble terminal complement complex (sC5b-9)., Results: In attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all, p <0.001), while the level of sC5b-9 was increased only in the NMOSD group. In MOGAD, there were no differences in the concentrations of complement analytes based on disease status. However, within AQP4-NMOSD, remission samples indicated a higher C1-INH level than attack samples (p=0.003). Notably, AQP4-NMOSD patients on medications during attack showed lower levels of iC3b ( p <0.001) and higher levels of C3 ( p =0.008), C1-INH ( p =0.004), and sC5b-9 ( p <0.001) compared to those not on medication. Among patients not on medication at the time of attack sampling, serum MOG-IgG cell-based assay (CBA) score had a positive correlation with iC3b and C1-INH levels (rho=0.764 and p =0.010, and rho=0.629 and p =0.049, respectively), and AQP4-IgG CBA score had a positive correlation with C1-INH level (rho=0.836, p =0.003)., Conclusions: This study indicates a higher prominence of complement pathway activation and subsequent C3 degradation in MOGAD compared to AQP4-NMOSD. On the other hand, the production of terminal complement complexes (TCC) was found to be more substantial in AQP4-NMOSD than in MOGAD. These findings suggest a strong regulation of the complement system, implying its potential involvement in the pathogenesis of MOGAD through mechanisms that extend beyond TCC formation., Competing Interests: EC received Biomedical Research Institute Fund from the Gyeongsang National University Hospital; J-HM is funded by and has received research support from the National Research Foundation of Korea MSIT and KHIDI and SMC Research and Development Grant. She has lectured, consulted and received honoraria from Bayer Healthcare, Merk, Biogen Idec, Sanofi, UCB, Samsung Bioepis, Mitsubishi Tanabe, Celltrion, Roche, Janssen, and Astrazeneca; BK has received funding and research support from the Korea Disease Control and Prevention Agency. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cho, Min, Waters, Jeon, Ju, Kim, Kim, Shin, Kang, Lim, Oh, Lee, Sohn, Lee, Oh, Kim, Huh, Cho, Seok, Kim and Kim.)