AUTHOR=Cho Eun Bin , Min Ju-Hong , Waters Patrick , Jeon Miyoung , Ju Eun-Seon , Kim Ho Jin , Kim Su-Hyun , Shin Ha Young , Kang Sa-Yoon , Lim Young-Min , Oh Sun-Young , Lee Hye Lim , Sohn Eunhee , Lee Sang-Soo , Oh Jeeyoung , Kim Sunyoung , Huh So-Young , Cho Joong-Yang , Seok Jin Myoung , Kim Byung-Jo , Kim Byoung Joon 

TITLE=Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1320094

DOI=10.3389/fimmu.2024.1320094

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>The sera of patients with MOGAD (from during an attack and remission; <italic>N</italic>=19 and <italic>N</italic>=9, respectively) and AQP4-NMOSD (<italic>N</italic>=35 and <italic>N</italic>=17), and healthy controls (<italic>N</italic>=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).</p></sec><sec><title>Results</title><p>In attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all, <italic>p</italic>&lt;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 (<italic>p</italic>&lt;0.001) and higher levels of C3 (<italic>p</italic>=0.008), C1-INH (<italic>p</italic>=0.004), and sC5b-9 (<italic>p</italic>&lt;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 <italic>p</italic>=0.010, and rho=0.629 and <italic>p</italic>=0.049, respectively), and AQP4-IgG CBA score had a positive correlation with C1-INH level (rho=0.836, <italic>p</italic>=0.003).</p></sec><sec><title>Conclusions</title><p>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.</p></sec>