A study recently published in leading journal Frontiers in Immunology contributes to further understanding about which components of the immune system are beneficial in multiple sclerosis (MS) and could help inform research on more targeted immunotherapies.
“In MS, B cells play a key role in inflammation, either by promoting it (pro-inflammatory signals) or reducing it (anti-inflammatory or regulatory signals),” said joint first author and postdoctoral researcher Dr Belinda Kaskow (Perron Institute, UWA and Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University).
“Our study identified a subset of anti-inflammatory or regulatory B cells that can control inflammation caused by T cells, both white blood cells. In people with MS, these regulatory B cells had lost their ability to control inflammation.
“Current treatments for MS work by modifying the immune system to reduce inflammation in the central nervous system. A notable group of these immunomodulatory therapies include ocrelizumab (Ocrevus) and ofatumumab (Kesimpta), which target a protein called CD20, found on the surface of most B cells and a small subset of T cells.
“While anti-CD20 therapies deplete B cells, this effect is not permanent, and B cells reappear in the blood. When they do, they seem to be ‘reset’ and can restore immune balance.
“In our study, we found that these anti-inflammatory regulatory B cells were increased only in the blood of people who responded well to anti-CD20 therapy. These individuals showed improved symptoms, compared to those who did not respond to the therapy.
“Although anti-CD20 therapies are highly effective at preventing MS relapses and delaying disease progression, depleting nearly an entire immune population is not ideal and can increase the risk of infections.
“This research is part of the ongoing efforts by the Demyelinating Diseases Research group at the Perron Institute, some of which is supported by MS Australia grants announced earlier this year. Our goal is to understand immune dysregulation in MS and develop more effective, targeted treatments with reduced side effects,” Dr Kaskow said.
Dr Kaskow is also a Lecturer at The University of Western Australia. The other joint first author is postdoctoral researcher Dr Johnna Varghese at Brigham and Women’s Hospital, Boston, USA.
Senior author Clare Baecher-Allan is an Assistant Professor of Neurology at the Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Boston, and was a mentor for Dr Kaskow during her postdoc fellowship at Brigham and Women’s Hospital and Harvard Medical School, Boston, before returning to Perth.