The relationship between serum astroglial and neuronal markers and AQP4 and MOG autoantibodies

Author:

Chatanaka Miyo K1,Avery Lisa M1,Pasic Maria D1,Sithravadivel Shanthan2,Rotstein Dalia2,Demos Catherine3,Cohen Rachel3,Gorham Taron3,Wang Mingyue3,Stengelin Martin3,Mathew Anu3,Wohlstadter Jacob3,Prassas Ioannis4,Diamandis Eleftherios P5

Affiliation:

1. University of Toronto

2. Unity Health Toronto

3. Meso Scale Discovery (United States)

4. University Health Network

5. Mount Sinai Hospital

Abstract

Abstract Background Certain demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) exhibit serum autoantibodies against aquaporin-4 (αAQP4) and myelin oligodendrocyte glycoprotein (αMOG). The variability of the autoantibody presentation warrants further research into subtyping each case. Methods To elucidate the relationship between astroglial and neuronal protein concentrations in the peripheral circulation with occurrence of these autoantibodies, 86 serum samples were analyzed using immunoassays. The protein concentration of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL) and tau protein was measured in 3 groups of subcategories of suspected NMOSD: αAQP4 positive (n = 20), αMOG positive (n = 32) and αMOG/αAQP4 seronegative (n = 34). Kruskal-Wallis analysis, univariate predictor analysis, and multivariate logistic regression with ROC curves were performed. Results GFAP and NFL concentrations were significantly elevated in the αAQP4 positive group (p = 0.003; p = 0.042, respectively), and tau was elevated in the αMOG/αAQP4 seronegative group (p < 0.001). A logistic regression model to classify serostatus was able to separate αAQP4 seropositivity using GFAP + tau, and αMOG seropositivity using tau. The areas under the ROC curves (AUCs) were 0.77 and 0.72, respectively. Finally, a combined seropositivity versus negative status logistic regression model was generated, with AUC = 0.80. Conclusion The 3 markers can univariately and multivariately classify with moderate accuracy the samples with seropositivity and seronegativity for αAQP4 and αMOG.

Publisher

Research Square Platform LLC

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