Evidence map›Paper›PMID 38326464›Full record

ArticleScientific reports2024

Anti-aquaporin-4 immune complex stimulates complement-dependent Th17 cytokine release in neuromyelitis optica spectrum disorders.

Shuhei Nishiyama, Jin Myong Seok, Amy E Wright, Itay Lotan, Takahisa Mikami, Natalia C Drosu, Natasha Bobrowski-Khoury, Monique R Anderson, Philippe A Bilodeau, Patrick Schindler and 5 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
6.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 16 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 16 institutions in 4 countries.

Shuhei NishiyamaDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA. SNISHIYAMA1@mgh.harvard.edu.
Jin Myong SeokDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Amy E WrightDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Itay LotanDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Takahisa MikamiDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Natalia C DrosuDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Natasha Bobrowski-KhouryDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Monique R AndersonDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Philippe A BilodeauDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Patrick SchindlerExperimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Friedemann PaulExperimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Masashi AokiDepartment of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Michael R YeamanGeffen School of Medicine at UCLA, Los Angeles, CA, USA.
Michael LevyDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Guthy-Jackson Charitable Foundation CIRCLES Study Group
Massachusetts General Hospital · USHarvard University · USGuthy-Jackson Charitable Foundation · USMax Delbrück Center · DEBrigham and Women's Hospital · USCleveland Clinic · USColumbia University Irving Medical Center · USHarbor–UCLA Medical Center · USStanford University · USSwedish Medical Center · USTohoku University · JPUniversity of British Columbia · CAUniversity of California, Los Angeles · USUniversity of Colorado Denver · USUniversity of Michigan · USUniversity of Utah · US

Funding

Developing Tolerization Therapies from a New T-cell Based Mouse Model of Neuromyelitis OpticaR01AI130548 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LEVY, MICHAEL · 2018 to 2022
$2.0M
NIAID NIH HHS R01 AI130548
6 · The paper itself

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.

Indexed as

Neuromyelitis OpticaAntigen-Antibody ComplexAquaporin 4AutoantibodiesComplement System ProteinsCytokinesHumansImmunoglobulin GInterleukin-17Interleukin-6Leukocytes, MononuclearRituximabAntigen-Antibody ComplexAquaporin 4AutoantibodiesComplement System ProteinsCytokinesImmunoglobulin GInterleukin-17Interleukin-6Rituximab

Identifiers

PMID38326464
PMCPMC10850367
OpenAlexW4391602380

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.