Treatment response to dimethyl fumarate is characterized by disproportionate CD8+T cell reduction in MS

被引:45
作者
Fleischer, Vinzenz [1 ]
Friedrich, Michaela [1 ]
Rezk, Ayman [2 ]
Buehler, Ulrike [1 ]
Witsch, Esther [1 ]
Uphaus, Timo [1 ]
Bittner, Stefan [1 ]
Groppa, Sergiu [1 ]
Tackenberg, Bjoern [3 ]
Bar-Or, Amit [2 ]
Zipp, Frauke [1 ]
Luessi, Felix [1 ]
机构
[1] Johannes Gutenberg Univ Mainz, Rmn2, Dept Neurol,Univ Med Ctr, Focus Program Translat Neurosci FTN & Immunol FZI, Langenbeckstr 1, D-55131 Mainz, Germany
[2] McGill Univ, Montreal Neurol Inst, Neuroimmunol Unit, Montreal, PQ, Canada
[3] Philipps Univ, Dept Neurol, Clin Neuroimmunol Grp, Marburg, Germany
关键词
Multiple sclerosis; dimethyl fumarate; treatment response; lymphocyte subsets; CD8+T cells; PLACEBO-CONTROLLED PHASE-3; LYMPHOCYTE COUNT PROFILES; ACID ESTERS; MULTIPLE-SCLEROSIS; ORAL BG-12; PATIENT; PML;
D O I
10.1177/1352458517703799
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: The effect of dimethyl fumarate (DMF) on circulating lymphocyte subsets and their contribution as predictors of clinical efficacy have not yet been investigated in multiple sclerosis (MS). Objective: To evaluate lymphocytes and lymphocyte subsets (analyzed 6 months after DMF start) in MS patients with and without disease activity after 1 year of treatment in a retrospective study. Methods: Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Untreated MS patients (n = 40) were compared to those 6 months after onset of DMF treatment (n = 51). Clinical and magnetic resonance imaging (MRI) disease activity of DMF-treated patients were assessed in the first year under treatment. Results: Stable patients showed significantly lower lymphocytes, CD4+ and CD8+ T cells as well as CD19+ B cells compared to active patients under DMF treatment. Furthermore, an increased CD4/CD8 ratio (p < 0.025) in stable patients indicated a disproportionate reduction of CD8+ T cells relative to CD4+ T cells. Reduced lymphocytes, CD8+ T cells, and CD19+ B cells 6 months after DMF start allowed prediction of the treatment response in the first year. Conclusion: DMF treatment response is reflected by lower circulating lymphocytes and specific lymphocyte subsets. Changes in the cellular immune profiles under DMF treatment are clinically relevant and might serve as a surrogate marker of treatment response.
引用
收藏
页码:632 / 641
页数:10
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