Studies of the immune profile in RAMBLE participants

Summary

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 secondary autoimmunity in approximately 36% of people treated with alemtuzumab.  

Data obtained from previous studies has shown the potential benefit of rituximab administration after alemtuzumab therapy in reducing the incidence of secondary autoimmunity. This study will explore the effect of low-dose rituximab administration in decreasing alemtuzumab-induced autoimmunity. 

The high incidence of autoimmunity observed after alemtuzumab treatment has been associated with an unsynchronised repopulation of B and T cells (types of immune cells) after alemtuzumab therapy. It has been suggested that the faster re-population of B cells in the absence of T lymphocytes might trigger the development of secondary autoimmunity. Additionally, higher baseline levels of the cytokine IL-21, a protein that helps control the immune system, have been observed in people who developed secondary autoimmunity compared to those who didn’t. Moreover, a genetic predisposition has been identified in people who developed secondary autoimmunity. This project will study the expected frequencies of gene expression 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 the pathological mechanisms underlying the development of secondary autoimmunity. Moreover, the aim is to gather valuable data of the effects of this alemtuzumab-rituximab co-therapy regimen to decrease the incidence of autoimmunity secondary to alemtuzumab therapy.