http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12776208&dopt=Abstract

Nat Rev Immunol 2003 Jun;3(6):483-92
Steinman L, Zamvil S.
Beckman Center for Molecular Medicine B002, Stanford University, Stanford, California 94305, USA.

Preface

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.

Summary

• 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.