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Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis

by Allard, John , Lad, Nagin , Austin, Angela , Steinman, Lawrence , Hermans, Guy , Strober, Samuel , Cannella, Barbara , Raine, Cedric S. , Brendolan, Andrea , Lock, Christopher , Kaminski, Naftali , Klonowski, Paul , Langer-Gould, Annette , Pedotti, Rosetta , Schadt, Eric , Garren, Hideki , Galli, Stephen J. , Oksenberg, Jorge R. , Heller, Renu

in Acute Disease / Animals / Autoimmune diseases / Autopsies / Autopsy / Chronic Disease / Chronic illnesses / Cluster analysis / Cytokines / Edema / Encephalomyelitis / Encephalomyelitis, Autoimmune, Experimental - genetics / Encephalomyelitis, Autoimmune, Experimental - pathology / Female / Gene expression / Granulocyte Colony-Stimulating Factor - physiology / Histopathology / Humans / Inflammation / Inflammation - genetics / Inflammation - pathology / Interferon-gamma - genetics / Interleukin-17 - genetics / Interleukin-6 - genetics / Lesions / Lymphocytes / Mice / Mice, Inbred C57BL / Multiple sclerosis / Multiple Sclerosis - genetics / Multiple Sclerosis - pathology / Nervous system / Neuropathology / Oligonucleotide Array Sequence Analysis / Pathology / Receptors, Fc - physiology / Reproducibility of Results / Transcription, Genetic

2002

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Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis

2002

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2002

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Journal Article

Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis

Allard, John,

Lad, Nagin,

Austin, Angela,

Steinman, Lawrence,

Hermans, Guy,

Strober, Samuel,

Cannella, Barbara,

Raine, Cedric S.,

Brendolan, Andrea,

Lock, Christopher,

Kaminski, Naftali,

Klonowski, Paul,

Langer-Gould, Annette,

Pedotti, Rosetta,

Schadt, Eric,

Garren, Hideki,

Galli, Stephen J.,

Oksenberg, Jorge R.,

Heller, Renu

2002

Overview

Microarray analysis of multiple sclerosis (MS) lesions obtained at autopsy revealed increased transcripts of genes encoding inflammatory cytokines, particularly interleukin-6 and -17, interferon-gamma and associated downstream pathways. Comparison of two poles of MS pathology--acute lesions with inflammation versus 'silent' lesions without inflammation--revealed differentially transcribed genes. Some products of these genes were chosen as targets for therapy of experimental autoimmune encephalomyelitis (EAE) in mice. Granulocyte colony-stimulating factor is upregulated in acute, but not in chronic, MS lesions, and the effect on ameliorating EAE is more pronounced in the acute phase, in contrast to knocking out the immunoglobulin Fc receptor common gamma chain where the effect is greatest on chronic disease. These results in EAE corroborate the microarray studies on MS lesions. Large-scale analysis of transcripts in MS lesions elucidates new aspects of pathology and opens possibilities for therapy.

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Publisher

Nature Publishing Group

Subject

Acute Disease

/ Animals

/ Autoimmune diseases

/ Autopsies

/ Autopsy

/ Chronic Disease

/ Chronic illnesses