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Neurology. 2014 Feb 25;82(8):681-90. doi: 10.1212/WNL.0000000000000146. Epub 2014 Jan 22.

Naive CD4 T-cell activation identifies MS patients having rapid transition to progressive MS.

Author information

From Neuroscience (E.Z., L.F.-G.), Department of Pathology (D.G.H.), and McGill Centre for Bioinformatics (M.H.), McGill University, Montreal; Neurology (J.A., A.B.-O., Y.L.), Montreal Neurological Hospital, Montreal, Canada; and Neurology (S.B.), UCSF, San Francisco, CA.

Erratum in

  • Neurology. 2014 Apr 1;82(13):1193.



Our objective was to determine whether altered naive CD4 T-cell biology contributes to development of disease progression in secondary progressive multiple sclerosis (SPMS).


We compared the naive CD4 T-cell gene expression profiles of 19 patients with SPMS and 14 healthy controls (HCs) using a whole-genome microarray approach. We analyzed surface protein expression of critical genes by flow cytometry after T-cell receptor (TCR) stimulation of naive CD4 T cells isolated from HCs and patients with SPMS.


Hierarchical clustering segregated patients with SPMS into 2 subgroups: SP-1, which had a short duration of relapsing-remitting multiple sclerosis (MS), and SP-2, which had a long duration of relapsing-remitting MS. SP-1 patients upregulated numerous immune genes, including genes within TCR and toll-like receptor (TLR) signaling pathways. SP-2 patients showed immune gene downregulation in comparison with HCs. We identified an SP-1-specific transcriptional signature of 3 genes (TLR4, TLR2, and chemokine receptor 1), and these genes had higher surface protein expression in SP-1 than in SP-2. After TCR stimulation for 48 hours, only SP-1 showed a progressive linear increase in TLR2 and TLR4 protein expression.


Differences in naive CD4 T-cell biology, notably of TCR and TLR signaling pathways, identified patients with MS with more rapid conversion to secondary progression, a critical determinant of long-term disability in MS.

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