Abstract
Objective: Early studies investigating Alemtuzumab (Lemtrada) in multiple sclerosis (MS) patients suggested that depletion of CD27+ memory B cells was a possible mechanism of action. Whether other B cell subsets are affected by Alemtuzumab is not known and was investigated in this in-depth phenotypic analysis of B cell subsets within alemtuzumab-treated MS patients.
Background: Alemtuzumab is a monoclonal antibody specific for CD52, which is expressed on mature lymphocytes. It is thought to work as a disease-modifying therapy in relapse-remitting MS by depleting autoreactive T and B cells.
Design/Methods: Peripheral blood mononuclear cells from MS patients after long-term (2 years-post) alemtuzumab treatment were stained with our panel of 40 isotope-conjugated antibodies. Mass cytometry, which combines flow cytometry with mass spectrometry, was then used to analyse and phenotype B cell subsets with unparalleled depth.
Results: Analysis of the mass cytometry data showed that long-term alemtuzumab-induced remission is associated with continuing low levels of CD27+ IgD− switched and CD27+ IgD− non-switched memory B cells 2 years-post initial treatment.
Conclusions: Mass cytometry revealed which B cell subsets are affected by alemtuzumab treatment after long periods of time. These studies will allow us to track efficacy and design new ways of targeting these B cells more specifically.
Disclosure: Dr. Marsh-Wakefield has nothing to disclose. Dr. Juillard has nothing to disclose. Dr. Ashhurst has nothing to disclose. Dr. McGuire has nothing to disclose. Dr. Byrne has nothing to disclose. Dr. Grau has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck. Dr. Grau has received research support from Merck and Sanofi-Genzyme. Dr. Hawke has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck, Sanofi Genzyme, and Novartis.
Disputes & Debates: Rapid online correspondence
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