An RNA Profile Identifies Two Subsets of Multiple Sclerosis Patients Differing in Disease Activity

被引：48
作者：
Ottoboni, Linda [1 ,2 ,3 ]
Keenan, Brendan T. [1 ,3 ]
Tamayo, Pablo [4 ]
Kuchroo, Manik [1 ]
Mesirov, Jill P. [4 ]
Buckle, Guy J. [2 ,5 ,6 ]
Khoury, Samia J. [2 ,5 ,6 ]
Hafler, David A. [3 ,7 ]
Weiner, Howard L. [2 ,5 ,6 ]
De Jager, Philip L. [1 ,2 ,3 ,5 ,6 ]
机构：
[1] Brigham & Womens Hosp, Dept Neurol, Inst Neurosci, Program Translat Neuropsychiat Genom, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA
[4] Broad Inst, Computat Biol & Bioinformat Program, Cambridge, MA 02139 USA
[5] Brigham & Womens Hosp, Dept Neurol, Partners Multiple Sclerosis Ctr, Boston, MA 02115 USA
[6] Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA
[7] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA
来源：
SCIENCE TRANSLATIONAL MEDICINE | 2012年 / 4卷 / 153期
关键词：
PLACEBO-CONTROLLED TRIAL; INTERFERON-BETA; MODEL; MRI;
D O I：
10.1126/scitranslmed.3004186
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
The multiple sclerosis (MS) patient population is highly heterogeneous in terms of disease course and treatment response. We used a transcriptional profile generated from peripheral blood mononuclear cells to define the structure of an MS patient population. Two subsets of MS subjects (MSA and MSB) were found among 141 untreated subjects. We replicated this structure in two additional groups of MS subjects treated with one of the two first-line disease-modifying treatments in MS: glatiramer acetate (GA) (n = 94) and interferon-beta (IFN-beta) (n = 128). One of the two subsets of subjects (MSA) was distinguished by higher expression of molecules involved in lymphocyte signaling pathways. Further, subjects in this MSA subset were more likely to have a new inflammatory event while on treatment with either GA or IFN-beta (P = 0.0077). We thus report a transcriptional signature that differentiates subjects with MS into two classes with different levels of disease activity.
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页数：7
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