Poster De Conférence Année : 2019

Compared CSF biomarker profile of AQP4-Ab, MOG-Ab and double seronegative NMOSD reveals specificities with potential therapeutic implications

Résumé

Background: Current neuromyelitis optica (NMO) spectrum disorder criteria stratify patients according to the aquaporin-4 (AQP4) antibody status. Among seronegative NMO (neg-NMO), some patients have antibodies against myelin oligodendrocyte glycoprotein (MOG) (MOG-NMO). Distinct molecular and cellular pathways (T-cells vs. B-cells) could explain clinical, therapeutic and pathological differences reported recently among these 3 groups. Objectives: To evaluate the level of cerebrospinal fluid (CSF) biomarkers in these 3 NMO subtypes as well as in multiple sclerosis, other inflammatory neurological disorders (OIND) and symptomatic controls (SC). Methods: Retrospective multicentric study including 21 MOG-NMO, 21 AQP4-NMO and 18 neg-NMO, 26 relapsing-remitting MS (RRMS), 17 primary progressive MS (PPMS), 25 OIND and 37 SC. We determined CSF levels of IL-1b, IL-6, IL-8, IL-10, IL-17a, CXCL-13, CD27, MCP-1, MMP-9, sICAM-1, sVCAM1 (multiplex ELISA, Thermo Fisher), chitinase 3-like protein 1 (CHI3L1, Microvue) and neurofilament-light chain (NFL, Uman Diagnostics). Descriptive statistical analyses were performed with PRISM. Results: CSF levels of CHI3L1 and MCP-1 were similar in the three NMO groups while other biomarkers were increased in AQP4-NMO compared to MOG-NMO and neg-NMO, except for NFL, with highest levels in neg-NMO. Increased CSF levels of CXCL-13, CD27 and IL-17a discriminated RRMS and AQP4-NMO from MOG-NMO and neg-NMO (p< 0.001, Mann Whitney test). MOG-NMO and neg-NMO were only differentiated by increased NFL in neg-NMO (p< 0.05). IL-6 (p< 0.001), MCP-1 (p< 0.01) and sVCAM-1 (p< 0.01) CSF levels were increased in all NMO groups compared to RRMS and PPMS (p< 0.001). Discussion: The CSF profiles of MOG-NMO and neg-NMO are different from AQP4-NMO, confirming the clinical and pathological differences recently reported. The only significant difference found between MOG-NMO and neg-NMO was a low NFL level in MOG-NMO, suggesting that, in this condition, axons are preserved that could explain the relatively good outcome associated to MOG-NMO patients. Most interestingly, we found an increase of B-cell markers (CXCL-13, CD27) in AQP4-NMO and in MS, but not in MOG-NMO or in neg-NMO, suggesting that B-cell therapies could be less effective in MOG-NMO and neg-NMO. Conclusion: Our study confirms that mechanisms in MOG and AQP4-associated disease are probably different and that B-cell depletion therapies might not be the best treatment in MOG-NMO and neg-NMO.

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Dates et versions

hal-04777152 , version 1 (12-11-2024)

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  • HAL Id : hal-04777152 , version 1

Citer

Eric Thouvenot, Lucile Du Trieu de Terdonck, Sara Mariotto, Renaud Cezar, Christophe Demattei, et al.. Compared CSF biomarker profile of AQP4-Ab, MOG-Ab and double seronegative NMOSD reveals specificities with potential therapeutic implications. 35th Annual Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2019), Sep 2019, Stockhlom, Sweden. Sage Journals, Multiple Sclerosis Journal, 25 (2 suppl.), pp.724-725 / P1323, 2019. ⟨hal-04777152⟩
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