@article{e64799adf4224351938efadfdd9c6095,
title = "Anti-aquaporin-4 immune complex stimulates complement-dependent Th17 cytokine release in neuromyelitis optica spectrum disorders",
abstract = "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.",
author = "Shuhei Nishiyama and Seok, {Jin Myong} and Wright, {Amy E.} and Itay Lotan and Takahisa Mikami and Drosu, {Natalia C.} and Natasha Bobrowski-Khoury and Anderson, {Monique R.} and Bilodeau, {Philippe A.} and Patrick Schindler and Friedemann Paul and Masashi Aoki and Yeaman, {Michael R.} and Michael Levy and Behne, {Jacinta M.} and Behne, {Megan K.} and Bennett, {Jeffrey L.} and Blaschke, {Terrence F.} and Tanuja Chitnis and Cook, {Lawrence J.} and Michael Levy and Planchon, {Sarah M.} and Pavle Repovic and Riley, {Claire S.} and Smith, {Terry J.} and Anthony Traboulsee and {R. Yeaman}, Michael",
note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",
year = "2024",
month = dec,
doi = "10.1038/s41598-024-53661-5",
language = "אנגלית",
volume = "14",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Research",
number = "1",
}