Research: CD4 T cell recovery after Alemtuzumab predicts disease return

Epub: Cossburn et al. Clinical relevance of differential lymphocyte recovery after alemtuzumab therapy for multiple sclerosis. Neurology. 2012 Dec.


OBJECTIVEAlemtuzumab is potentially a highly effective treatment for relapsing multiple sclerosis (MS) acting via complement-mediated lysis of circulating lymphocytes. Variability in post-treatment lymphocyte recovery time is observed, with some patients showing striking durability in the efficacy of treatment. This study aims to establish whether this observed variation affects clinical and imaging parameters of disease activity.

METHODSA total of 56 patients were followed for a median of 39.5 months post alemtuzumab treatment with interval clinical assessments, lymphocyte immunophenotyping, and MRI. Timing and degree of CD4+, CD8+ (T cell), and CD19+ (B cell) recovery were correlated with the re-emergence of disease activity defined as clinical relapse, increasing disability, and new T2/enhancing lesions on MRI.

RESULTSNew disease activity was recorded in 14% of patients. Mean time to CD19+, CD8+, and CD4+ reconstitution was 6, 10, and 36 months. No differences were observed in CD8+ and CD19+ reconstitution between patients with active disease and those in remission. Patients with active disease showed an accelerated recovery of CD4+ cells (p = 0.001) with a difference in absolute CD4+ counts at 24 months (p = 0.009). CD4+ counts <388.5 × 10(6) cells/mL predicted MRI stability.

CONCLUSIONSDifferential lymphocyte recovery in MS following alemtuzumab may be a biomarker for relapse and also inform monitoring and treatment protocols.


There is not much hard evidence to implicate CD4+ T cells as drivers of MS, yet it is clear that they are drivers in autoimmune diseases in all animal models. This study suggests that when CD4 T cell counts return after depletion with Alemtuzumab, disease can become active again.

The CD4 antibody trial was in my opinion an example of a messed up trial....but they did not deplete aggressively at that time because AIDS had just arrived and there was a worry about taken white blood cells below 200 cells per microlitre. This level of depletion in the CD4 antibody Trial was insignificant compared to that induced by Alemtuzumab and even in EAE this level of depletion was not enough to stop disease. Furthermore, the CD4 antibody used did not deplete memory T cells that well so was perhaps doomed before it started.

This CD4 Trial was led by a Young Prof Miller from UCLP. Remember to come see the Older Prof Miller at the Research Day as he is another of those famous Neuros from UCLP coming to talk with you.

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