This study will explore the mechanisms by which alemtuzumab works in the treatment of multiple sclerosis (MS), and how it leads to the development of other autoimmune diseases in approximately 36% of people treated.
Data obtained from previous studies has shown the potential benefit of rituximab administration after alemtuzumab therapy in reducing the incidence of other autoimmune diseases. This study will explore the effect of low-dose rituximab administration in decreasing alemtuzumab-induced autoimmune disease.
The development of other autoimmune diseases following alemtuzumab treatment is linked with B and T cells (types of immune cells) not growing back at the same rate after treatment. It has been suggested that the faster re-population of B cells in the absence of T cells might trigger the development of other autoimmune diseases. Additionally, higher baseline levels of the cytokine IL-21, a protein that helps control the immune system, have been observed in people who developed other autoimmune diseases compared to those who didn’t. Moreover, a genetic predisposition has been identified in people who developed secondary autoimmunity.
This project will study how often certain genes are active in people who develop secondary autoimmunity compared to those who don’t.
Ms Sofia Jimenez Sanchez’s focus is to better understand the mechanisms by which alemtuzumab works in the treatment of MS, and how this leads to the development of secondary autoimmunity. Moreover, the aim is to gather valuable data on the effects of this alemtuzumab-rituximab co-therapy regimen to decrease the incidence of autoimmunity secondary to alemtuzumab therapy.
As of March 2025, Ms Jimenez Sanchez has recruited ten participants for her PhD project within the RAMBLE study. Blood samples from participants have been collected for genetic and viral load studies, with most also taking part in cytokine and immune cell analyses. Preliminary findings show that alemtuzumab leads to rapid B cell repopulation, while rituximab results in a slower return of B cells, supporting its potential role in reducing treatment-related autoimmunity.
The detailed analysis of the immune system has been completed in four participants, and follow-up will continue over the next three years to track longer-term immune responses and the development of secondary autoimmunity. Despite some participants withdrawing from the project, valuable data has been obtained through partial participation in key blood sample collection.
In parallel, Ms Jimenez Sanchez completed and published a systematic review titled “The role of alemtuzumab in the development of secondary autoimmunity in multiple sclerosis” in the Journal of Neuroinflammation, providing important context for the ongoing clinical study.
Jimenez Sanchez, A., & Broadley, S. (2024). The role of alemtuzumab in the development of secondary autoimmunity: A systematic review. Journal of Neuroinflammation, 21(1), Article 70. https://doi.org/10.1186/s12974-024-03263-9
Updated 31 March 2025
Donald and Joan Wilson Foundation
$105,000
2023
3 years
Current project
