Key Points
Large-scale analysis of the messenger RNA transcripts that are expressed in diseased tissues can enable new components of pathways resulting in autoimmunity to be identified.
Large-scale sequencing can be carried out using robotic sequences of libraries, or using oligonucleotide microarrays.
The identification of new targets that are involved in the pathogenesis of multiple sclerosis (MS) is discussed.
Osteopontin is an important transcript found in MS lesions, and it modulates T helper 1 (TH1)-cell-mediated autoimmunity.
Leptin is found in MS lesions and it modulates the TH1–TH2 balance.
Statins not only lower cholesterol, but are also found in MS lesions and influence TH1-cell-mediated autoimmunity.
Several molecules that are involved in allergic responses, including histamine, also modulate autoimmunity.
Abstract
Large-scale analyses of messenger RNA transcripts and autoantibody responses, taken from the actual sites of disease, provide us with an unprecedented view of the complexity of autoimmunity. Despite an appreciation of the large number of pathways and pathological processes that are involved in these diseases, a few practical targets and several new strategies have emerged from these studies. This review focuses on multiple sclerosis and on the approaches that are being used to identify new targets that might be manipulated to control this disease.
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Acknowledgements
This work was funded, in part, by the Phil N. Allen Trust, the National Institutes of Health, the National Multiple Sclerosis Society, the Nancy Davis Foundation, the Maislin Foundation and the Wadsworth Foundation. L.S. has founded two biotechnology companies, Neurocrine Biosciences and Bayhill Therapeutics.
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Glossary
- MICROGLIAL CELLS
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Bone-marrow-derived macrophages that are resident in the central nervous sytem.
- OLIGONUCLEOTIDE MICROARRAYS
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Short chains of nucleotides are chemically coupled to a solid surface. There, they hybridize with complementary DNA sequences.
- SINGLE-NUCLEOTIDE POLYMORPHISMS
-
(SNPs). Single base-pair changes that are inherited as Mendelian traits and might associate with a trait such as susceptibility to disease.
- EXPRESSED SEQUENCE TAG
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(EST). A single-pass, short read of complementary DNA that is generated from a transcribed region of the genome.
- EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
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(EAE). Refers to a set of related animal models of multiple sclerosis. Typically, disease is induced by the injection of components of myelin, which leads to demyelination in the central nervous system.
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Steinman, L., Zamvil, S. Transcriptional analysis of targets in multiple sclerosis. Nat Rev Immunol 3, 483–492 (2003). https://doi.org/10.1038/nri1108
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DOI: https://doi.org/10.1038/nri1108
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