Analysis of natural killer cell status in Alemtuzumab MS patients
Research type
Research Study
Full title
Analysis of natural killer cell status in Alemtuzumab treated multiple sclerosis patients: suppression and reconstitution?
IRAS ID
154523
Contact name
Ute Meier
Contact email
Duration of Study in the UK
0 years, 6 months, 31 days
Research summary
The humanised antibody Alemtuzumab targets the CD52 antigen expressed on T- and B-cells, monocytes and macrophages. It is also expressed on natural killer (NK)-cells, however, its level of expression is lower on these cells. Alemtuzumab has been used since 1991 for the treatment of multiple sclerosis (MS) at Addenbrooke’s Hospital, UK. Alemtuzumab treatment leads to rapid and sustained lymphocyte depletion. Lymphocytes start to reconstitute 18 months post-treatment. The effect of Alemtuzumab on the functionality and frequency of NK-cell subsets has not been studied so far.
Several MS treatments impact on the NK-cell status. However, whether these alterations are directly involved in the therapeutic treatment effect remains currently unknown. Several studies have reported NK-cell alterations in MS patients and we are just starting to understand how some treatments impact on these important innate lymphocyte subsets.
Alteration in the distribution of NK-cell subsets may have profound effects on the ability of the immune system to kill invading pathogens and cancer cells. It is well established that NK-cells are pivotal for the successful instruction and regulation of adaptive immune responses. An interesting line of investigation is, therefore, their effect on potentially auto-reactive T-cells. However, the interaction between NK-cells and auto-reactive T-cells, particularly within the activated CD4+ T cell pool, has not been explored in detail in patients with MS. Recent findings highlight that activated CD56bright NK-cells can kill autologous CD4+ T-cells and may suggest a novel way of immunoregulation by CD56bright NK-cells.
The objective of this study is the analysis of the natural killer (NK) cell status of Alemtuzumab treated MS patients by assessing the functional activity of the CD56dim and CD56high NK cell subsets. We will use two key functional read-outs: NK cell killing activity of NK target cell line and pro-inflammatory cytokine production.REC name
London - City & East Research Ethics Committee
REC reference
14/LO/2185
Date of REC Opinion
29 Nov 2014
REC opinion
Favourable Opinion