{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:36:00Z","timestamp":1792683360845,"version":"4.5.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018688","name":"Korea Disease Control and Prevention Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018688","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats: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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The sera of patients with MOGAD (from during an attack and remission; <jats:italic>N<\/jats:italic>=19 and <jats:italic>N<\/jats:italic>=9, respectively) and AQP4-NMOSD (<jats:italic>N<\/jats:italic>=35 and <jats:italic>N<\/jats:italic>=17), and healthy controls (<jats:italic>N<\/jats: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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all, <jats:italic>p<\/jats:italic>&amp;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 (<jats:italic>p<\/jats:italic>&amp;lt;0.001) and higher levels of C3 (<jats:italic>p<\/jats:italic>=0.008), C1-INH (<jats:italic>p<\/jats:italic>=0.004), and sC5b-9 (<jats:italic>p<\/jats:italic>&amp;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 <jats:italic>p<\/jats:italic>=0.010, and rho=0.629 and <jats:italic>p<\/jats:italic>=0.049, respectively), and AQP4-IgG CBA score had a positive correlation with C1-INH level (rho=0.836, <jats:italic>p<\/jats:italic>=0.003).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats: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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1320094","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T04:35:26Z","timestamp":1710995726000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder"],"prefix":"10.3389","volume":"15","author":[{"given":"Eun 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