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MS risk genes are transcriptionally regulated in CSF leukocytes at relapse

Journal article
Authors Margareta Jernås
Clas Malmeström
Markus Axelsson
Caroline Olsson
Intawat Nookaew
Hans Wadenvik
Henrik Zetterberg
Kaj Blennow
Jan Lycke
Mats Rudemo
Bob Olsson
Published in Multiple sclerosis (Houndmills, Basingstoke, England)
Volume 19
Issue 4
Pages 403-410
ISSN 1477-0970
Publication year 2013
Published at Institute of Clinical Sciences, Department of Radiation Physics
Institute of Neuroscience and Physiology
Department of Mathematical Sciences, Mathematical Statistics
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 403-410
Language en
Links dx.doi.org/10.1177/1352458512455466
Keywords Autoimmunity, T-cell, multiple sclerosis, microarray
Subject categories Radiological physics

Abstract

BACKGROUND: Infiltrating T-helper cells, cytotoxic T-cells, B-cells and monocytes are thought to mediate the damage to myelin, oligodendrocytes and axons in multiple sclerosis (MS), which results in progressive disability. OBJECTIVE: The objective of this paper is to explore gene expression profiles of leukocytes in the cerebrospinal fluid (CSF) compartment of MS patients during relapse. METHODS: Global gene expression was analyzed by DNA microarray analysis of cells in CSF from MS patients and controls, and verifications were performed with real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Fifty percent of the recently described risk genes for MS and 28% of non-risk genes were differently expressed in MS patients compared to controls (χ(2)-test, p=7.7 × 10(-5)). Genes involved in T- and NK-cell processes were up-regulated, and genes involved in processes targeting innate immunity or B-cells were down-regulated in MS. Increased expression of EDN1 and CXCL11 and decreased expression of HMOX1 was verified with real-time PCR and increased expression of CXCL13 was verified with ELISA in CSF. CONCLUSION: DNA microarray analysis is useful in identifying differently expressed genes in CSF leukocytes, which may be important in MS in vivo. Our findings suggest that many of the risk genes for MS are differently expressed in the disease-mediating leukocytes that penetrate the blood-brain barrier.

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