Naive B cells in neuromyelitis optica spectrum disorders: impact of steroid use and relapses
| Autor: | Jamie van Langelaar, Marie-José Melief, Annet F Wierenga-Wolf, Liza Rijvers, Beatrijs H.A. Wokke, Malou Janssen, Joost Smolders, YuYi Wong, Arlette L. Bruijstens, E Daniëlle van Pelt, Marvin M van Luijn |
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| Přispěvatelé: | Neurology, Immunology |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Naive B cell aquaporin-4 plasmablasts myelin oligodendrocyte glycoprotein Myelin oligodendrocyte glycoprotein transitional B cells 03 medical and health sciences Myelin TLR9 0302 clinical medicine Medicine Neuromyelitis optica biology business.industry AcademicSubjects/SCI01870 Multiple sclerosis General Engineering medicine.disease Oligodendrocyte eye diseases 030104 developmental biology Aquaporin 4 medicine.anatomical_structure Immunology biology.protein Original Article AcademicSubjects/MED00310 Antibody business 030217 neurology & neurosurgery |
| Zdroj: | Brain Communications Brain Communications, 2(2):197. Oxford University Press |
| ISSN: | 2632-1297 |
| Popis: | Neuromyelitis optica spectrum disorders are a group of rare, but severe autoimmune diseases characterized by inflammation of the optic nerve(s) and/or spinal cord. Although naive B cells are considered key players by escaping central tolerance checkpoints, it remains unclear how their composition and outgrowth differ in patients with neuromyelitis optica spectrum disorders. Under complete treatment-naive circumstances, we found that naive mature/transitional B-cell ratios were reduced in the blood of 10 patients with aquaporin-4 immunoglobulin G-positive disease (neuromyelitis optica spectrum disorders) as compared to 11 both age- and gender-matched healthy controls, eight patients with myelin oligodendrocyte glycoprotein-immunoglobulin G-associated disorders and 10 patients with multiple sclerosis. This was the result of increased proportions of transitional B cells, which were the highest in patients with neuromyelitis optica spectrum disorders with relapses and strongly diminished in a separate group of nine patients with neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein-immunoglobulin G-associated disorders who received corticosteroid treatment. These findings need to be confirmed in longitudinal studies. For purified naive mature B cells of seven patients with neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein-immunoglobulin G-associated disorders with relapses, Toll-like receptor 9 ligand synergized with interferon-γ to enhance plasmablast formation during germinal centre-like cultures. This was not seen for 11 patients without relapses and nine healthy controls. In the neuromyelitis optica spectrum disorders group, in vitro plasmablast formation corresponded to total and anti-aquaporin-4 immunoglobulin G secretion, of which the latter was found only for relapsing cases. These data indicate that naive B-cell homoeostasis is different and selectively targeted by corticosteroids in patients with neuromyelitis optica spectrum disorders. This also supports further exploration of naive B cells for their use in Toll-like receptor 9-dependent in vitro platforms in order to predict the activity of neuromyelitis optica spectrum disorders. Circulating transitional and not naive mature B cells show increased frequencies and seem to be selectively targeted by corticosteroids in patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorders. Naive mature B cells of patients with relapses preferentially develop into aquaporin-4 immunoglobulin G-producing plasmablasts in vitro under interferon-gamma- and Toll-like receptor 9-inducing conditions. Graphical Abstract Graphical Abstract |
| Databáze: | OpenAIRE |
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