T cell gene expression profiling identifies distinct subgroups of Japanese multiple sclerosis patients.
To clarify the molecular background underlying the heterogeneity of multiple sclerosis (MS), we characterized the gene expression profile of peripheral blood CD3+ T cells isolated from MS and healthy control (CN) subjects by using a cDNA microarray. Among 1258 cDNAs on the array, 286 genes were expressed differentially between 72 untreated Japanese MS patients and 22 age- and sex-matched CN subjects. When this set was used as a discriminator for hierarchical clustering analysis, it identified four distinct subgroups of MS patients and five gene clusters differentially expressed among the subgroups. One of these gene clusters was overexpressed in MS versus CN, and particularly enhanced in the clinically most active subgroup of MS. After 46 of the MS patients were treated with interferon-beta (IFNbeta-1b) for two years, IFNbeta responders were clustered in two of the four MS subgroups. Furthermore, the IFNbeta responders differed from nonresponders in the kinetics of IFN-responsive genes at 3 and 6 months after starting IFNbeta treatment. These results suggest that T-cell gene expression profiling is valuable to identify distinct subgroups of MS associated with differential disease activity and therapeutic response to IFNbeta.
Department of Immunology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
Jun-ichi
J
Satoh
Megumi
M
Nakanishi
Fumiko
F
Koike
Hiroyuki
H
Onoue
Toshimasa
T
Aranami
Toshiyuki
T
Yamamoto
Mitsuru
M
Kawai
Seiji
S
Kikuchi
Kyouichi
K
Nomura
Kazumasa
K
Yokoyama
Kohei
K
Ota
Toshiro
T
Saito
Masayuki
M
Ohta
Sachiko
S
Miyake
Takashi
T
Kanda
Toshiyuki
T
Fukazawa
Takashi
T
Yamamura
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D025341:Principal Component Analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D016899:Interferon-beta