No autoimmune diseases can currently be cured, only treated, and this is also true for neuromyelitis optica spectrum disorder (NEMOSD). Neuromyelitis optica disorder spectrum is one of them and it causes inflammation of the central nervous system, leading to vision and sensory loss, weakness and bladder dysfunction. The condition, which sometimes flares up in waves, has a treatment consisting of blinding the immune system to inflammation-promoting signals. But its biological action is broad and so it is also not understood why it doesn’t work in some patients and how to effectively ascertain which is the case. A Kobe University study of how the treatment acts on the immune system shows that it shifts the balance of types of immune cells. This finding may represent a step toward the development of personalized medicine for autoimmune diseases.
Scientists focused on B lymphocytes, the specialized cells elaborating all the antibodies for our necessities. B cells are a type of key immune cells that respond to inflammatory signals, and in autoimmune diseases like NMOSD, they produce antibodies against part of the body itself, exacerbating the condition. Therapies that inhibit inflammatory signals were therefore expected to change the activity of B cells in NMOSD. Since researchers observed that B cells were still present in the blood of patients after treatment, they decided to investigate the possibility that they were changing into a different type of B cell. They refer to so-called “regulatory B-cells,” (Bregs) a type of B lymphocyte that attenuates the immune system’s activity by secreting anti-inflammatory cytokines and is thought to play an important role in keeping the body’s immune system from becoming too active, and in the case of autoimmune diseases may prevent disease flares.
With their investigation, they focused on B cells in patients with NEMOSD, hypothesizing that IL-6R antibodies enables B cells to acquire regulatory functions by producing the anti-inflammatory cytokine IL-10. Then they created an experimental model of the immune cells during an NEMOSD flare and could thus trace the effect of the drug on the different kinds of B cells. Double negative B cells (DNs; CD19+ IgD–, CD27–) and plasmablasts (PBs; CD19+, CD27hi, CD38hi) were observed to expand in patients with NMSOD during the acute attacks. In the in vitro model, IL-6R antobidy satralizumab increased IL-10 expression in B cells. Notably, IL-10 expression increased in plasmablasts but not in DNs. Using RNA sequencing, CD200 was identified as a marker of regulatory plasmablasts among the differentially expressed upregulated genes. CD200+ plasmablasts produced more IL-10 than CD200- counterpart.
Furthermore, patients with NEMOSD who received satralizumab had a higher proportion of CD200+ plasmablasts than patients during the acute attacks. Therefore, it is true that each autoimmunity has complex cellular and signal transmission regulations (cytokine networks), which carries a molecular and biological signature that supports the disease and makes it progress. Understanding this also in neuromyelitis optica is essential to develop targeted drugs. Dr Chihara, leader neurologist at the Kobe University stated: “The essence of autoimmune diseases is a breakdown of autoimmune tolerance, the system that prevents us from attacking our own bodies. Our ultimate goal is to cure the disease by restoring this autoimmune tolerance, and the results of this study show one aspect of our work towards this goal”.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Akatani R et al. Neurol Neuroimmunol Neuroinflamm. 2024 Jul; 11(4):e200266.
Matsuoka T et al. Neurol Neuroimmunol Neuroinflamm. 2023 Oct 20; 11(1):e200173.
Hara A, Chihara N, Akatani R et al. Front Immunol. 2022 Dec 8; 13:1048428.