D. Van Pelt

MS Center ErasMS, Erasmus MC Neurology

Author Of 1 Presentation

Neuromyelitis Optica and Anti-MOG Disease Oral Presentation

HT06.03 - Naive B cells in neuromyelitis optica spectrum disorders: impact of steroid use and relapse occurrence

Speakers
Presentation Number
HT06.03
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease
Lecture Time
10:39 - 10:51

Abstract

Background

Neuromyelitis optica spectrum disorders (NMOSD) are a group of rare, but severe autoimmune diseases characterized by antibody-driven inflammation of mainly the ocular nerves and spinal cord. Although naive B cells are considered key players, it remains unknown whether their composition and outgrowth differ between serological NMOSD subgroups.

Objectives

We examined how ex vivo proportions and germinal center-like development of naive B cells are related to AQP4- and MOG-IgG serostatus, steroid treatment and relapse occurrence in NMOSD.

Methods

The presence of blood transitional, naive mature and both switched and unswitched memory B cells was determined in 10 AQP4- and 8 MOG-IgG-positive NMOSD patients without any form of previous immune suppressive treatment. Results were compared to 9 steroid-treated AQP4- or MOG-IgG-positive patients, 20 age- and gender-matched healthy controls (HCs) and 10 treatment-naive RRMS patients. Furthermore, naive B cells were cultured under T-bet-inducing, germinal center-like conditions for 11 days to address plasmablast formation in vitro.

Results

Under complete treatment-naive circumstances, naive mature/transitional B-cell ratios were significantly reduced in AQP4-IgG-positive NMOSD vs MOG-IgG-positive NMOSD, MS and HC groups. This was caused by increased proportions of transitional B cells, which were the highest in 2 AQP4-IgG-positive cases with relapsing disease (35% and 44% of the total B-cell pool). In steroid-treated patients, transitional B-cell proportions were strongly diminished and correlated negatively with time since start of treatment. For naive B cells from 7 relapsing NMOSD patients, TLR9 ligand CpG synergized with IFN-γ to enhance plasmablast formation in IL-21/CD40L-containing cultures. This was not seen for 11 non-relapsing patients or 9 HCs. IFN-γ- and CpG-induced naive B cells showed increased secretion of total IgG in the AQP4-IgG-positive group, and especially for patients with relapsing disease. In vitro-induced AQP4-IgG secretion was found for 3 relapsing but not for 6 non-relapsing patients, which was enhanced by IFN-γ and CpG (2 out of 3 relapsing patients). MOG-IgG was not detected in any of the naive B-cell culture supernatants of 4 relapsing and 4 non-relapsing MOG-IgG-positive patients.

Conclusions

These findings reveal that naive B-cell homeostasis is different and affected by steroid treatment amongst NMOSD subgroups, and offers a first rationale for exploring TLR9-dependent in vitro platforms to predict NMOSD activity.

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