Anti-aquaporin-4 immune complex stimulates complement-dependent Th17 cytokine release in neuromyelitis optica spectrum disorders
© 2024. The Author(s)..
Proinflammatory cytokines, such as (IL: interleukin) IL-6 and IL-17A, and complement fixation are critical in the immunopathogenesis of neuromyelitis optica spectrum disorders (NMOSD). Blocking the IL-6 receptor or the C5 complement pathway reduces relapse risk. However, the role of interleukin (IL)-6 and complement in aquaporin-4 (AQP4) autoimmunity remains unclear. To investigate the role of the anti-AQP4 immunoglobulin (AQP4-IgG)/AQP4 immunocomplex on the induction and profile of ex vivo cytokine and surface marker expression in peripheral blood mononuclear cells (PBMC) culture. Isolated PBMCs obtained from 18 patients with AQP4-IgG-seropositive-NMOSD (8 treatment-naive, 10 rituximab-treated) or ten healthy controls were cultured with AQP4-immunocomplex with or without complement. Changes in PBMC surface markers and cytokine expression were profiled using flow cytometry and ELISA. PBMCs derived from treatment-naive NMOSD patients stimulated with a complex mixture of serum complement proteins produced significant elevations of IL-17A and IL-6. Rituximab-treated patients also exhibited higher IL-6 but not IL-17A release. IL-6 and IL-17A elevations are not observed without complement. Co-stimulation of PBMCs with AQP4-IgG/AQP4 immunocomplex and complement prompts a Th17-biased response consistent with the inflammatory paradigm observed in NMOSD. A possible inflammation model is proposed via antigen-specific autoreactive peripheral blood cells, including NK/NKT cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Scientific reports - 14(2024), 1 vom: 07. Feb., Seite 3146 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nishiyama, Shuhei [VerfasserIn] |
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| Links: |
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| Themen: |
4F4X42SYQ6 |
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| Anmerkungen: |
Date Completed 09.02.2024 Date Revised 11.02.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-024-53661-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368156966 |
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| 245 | 1 | 0 | |a Anti-aquaporin-4 immune complex stimulates complement-dependent Th17 cytokine release in neuromyelitis optica spectrum disorders |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Proinflammatory cytokines, such as (IL: interleukin) IL-6 and IL-17A, and complement fixation are critical in the immunopathogenesis of neuromyelitis optica spectrum disorders (NMOSD). Blocking the IL-6 receptor or the C5 complement pathway reduces relapse risk. However, the role of interleukin (IL)-6 and complement in aquaporin-4 (AQP4) autoimmunity remains unclear. To investigate the role of the anti-AQP4 immunoglobulin (AQP4-IgG)/AQP4 immunocomplex on the induction and profile of ex vivo cytokine and surface marker expression in peripheral blood mononuclear cells (PBMC) culture. Isolated PBMCs obtained from 18 patients with AQP4-IgG-seropositive-NMOSD (8 treatment-naive, 10 rituximab-treated) or ten healthy controls were cultured with AQP4-immunocomplex with or without complement. Changes in PBMC surface markers and cytokine expression were profiled using flow cytometry and ELISA. PBMCs derived from treatment-naive NMOSD patients stimulated with a complex mixture of serum complement proteins produced significant elevations of IL-17A and IL-6. Rituximab-treated patients also exhibited higher IL-6 but not IL-17A release. IL-6 and IL-17A elevations are not observed without complement. Co-stimulation of PBMCs with AQP4-IgG/AQP4 immunocomplex and complement prompts a Th17-biased response consistent with the inflammatory paradigm observed in NMOSD. A possible inflammation model is proposed via antigen-specific autoreactive peripheral blood cells, including NK/NKT cells | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Seok, Jin Myong |e verfasserin |4 aut | |
| 700 | 1 | |a Wright, Amy E |e verfasserin |4 aut | |
| 700 | 1 | |a Lotan, Itay |e verfasserin |4 aut | |
| 700 | 1 | |a Mikami, Takahisa |e verfasserin |4 aut | |
| 700 | 1 | |a Drosu, Natalia C |e verfasserin |4 aut | |
| 700 | 1 | |a Bobrowski-Khoury, Natasha |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Monique R |e verfasserin |4 aut | |
| 700 | 1 | |a Bilodeau, Philippe A |e verfasserin |4 aut | |
| 700 | 1 | |a Schindler, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Paul, Friedemann |e verfasserin |4 aut | |
| 700 | 1 | |a Aoki, Masashi |e verfasserin |4 aut | |
| 700 | 1 | |a Yeaman, Michael R |e verfasserin |4 aut | |
| 700 | 1 | |a Levy, Michael |e verfasserin |4 aut | |
| 700 | 0 | |a Guthy-Jackson Charitable Foundation CIRCLES Study Group |e verfasserin |4 aut | |
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| 700 | 1 | |a Behne, Megan K |e investigator |4 oth | |
| 700 | 1 | |a Bennett, Jeffrey L |e investigator |4 oth | |
| 700 | 1 | |a Blaschke, Terrence F |e investigator |4 oth | |
| 700 | 1 | |a Chitnis, Tanuja |e investigator |4 oth | |
| 700 | 1 | |a Cook, Lawrence J |e investigator |4 oth | |
| 700 | 1 | |a Levy, Michael |e investigator |4 oth | |
| 700 | 1 | |a Planchon, Sarah M |e investigator |4 oth | |
| 700 | 1 | |a Repovic, Pavle |e investigator |4 oth | |
| 700 | 1 | |a Riley, Claire S |e investigator |4 oth | |
| 700 | 1 | |a Smith, Terry J |e investigator |4 oth | |
| 700 | 1 | |a Traboulsee, Anthony |e investigator |4 oth | |
| 700 | 1 | |a R Yeaman, Michael |e investigator |4 oth | |
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