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| Item Type: | Article |
|---|---|
| Title: | Serum proteomics distinguish subtypes of NMO spectrum disorder and MOG antibody-associated disease and highlight effects of B-cell depletion |
| Creators Name: | Gawde, S., Siebert, N., Ruprecht, K., Kumar, G., Ko, R.M., Massey, K., Guthridge, J.M., Mao-Draayer, Y., Schindler, P., Hastermann, M., Pardo, G., Paul, F. and Axtell, R.C. |
| Abstract: | BACKGROUND AND OBJECTIVES: AQP4 antibody-positive NMOSD (AQP4-NMOSD), MOG antibody-associated disease (MOGAD), and seronegative NMOSD (SN-NMOSD) are neuroautoimmune conditions that have overlapping clinical manifestations. Yet, important differences exist in these diseases, particularly in B-cell depletion (BCD) efficacy. Yet, the biology driving these differences remains unclear. Our study aims to clarify biological pathways distinguishing these diseases beyond autoantibodies and investigate variable BCD effects through proteomic comparisons. METHODS: In a retrospective study, 1,463 serum proteins were measured in 53 AQP4-NMOSD, 25 MOGAD, 18 SN-NMOSD, and 49 healthy individuals. To identify disease subtype-associated signatures, we examined serum proteins in patients without anti-CD20 B-cell depletion (NoBCD). We then assessed the effect of BCD treatment within each subtype by comparing proteins between BCD-treated and NoBCD-treated patients. RESULTS: In NoBCD-treated patients, serum profiles distinguished the 3 diseases. AQP4-NMOSD showed elevated type I interferon-induced chemokines (CXCL9 and CXCL10) and TFH chemokine (CXCL13). MOGAD exhibited increased cytotoxic T-cell proteases (granzyme B and granzyme H), while SN-NMOSD displayed elevated Wnt inhibitory factor 1, a marker for nerve injury. Across all subtypes, BCD-treated patients showed reduction of B-cell-associated proteins. In AQP4-NMOSD, BCD led to a decrease in several inflammatory pathways, including IL-17 signaling, cytokine storm, and macrophage activation. By contrast, BCD elevated these pathways in patients with MOGAD. BCD had no effect on these pathways in SN-NMOSD. DISCUSSION: Proteomic profiles show unique biological pathways that distinguish AQP4-NMOSD, MOGAD, or SN-NMOSD. Furthermore, BCD uniquely affects inflammatory pathways in each disease type, providing an explanation for the disparate therapeutic response in AQP4-NMOSD and MOGAD. |
| Keywords: | Aquaporin 4, Autoantibodies, B-Lymphocytes, Myelin-Oligodendrocyte Glycoprotein, Neuromyelitis Optica, Proteomics, Retrospective Studies |
| Source: | Neurology Neuroimmunology & Neuroinflammation |
| ISSN: | 2332-7812 |
| Publisher: | American Academy of Neurology |
| Volume: | 11 |
| Number: | 4 |
| Page Range: | e200268 |
| Date: | July 2024 |
| Official Publication: | https://doi.org/10.1212/nxi.0000000000200268 |
| PubMed: | View item in PubMed |
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