MS risk genes are transcriptionally regulated in CSF leukocytes at relapse
Journal article, 2013

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.

multiple sclerosis





Margareta Jernås

University of Gothenburg

Clas Malmeström

University of Gothenburg

Markus Axelsson

University of Gothenburg

Caroline Olsson

University of Gothenburg

Intawat Nookaew

Chalmers, Chemical and Biological Engineering, Life Sciences

Hans Wadenvik

University of Gothenburg

Henrik Zetterberg

University of Gothenburg

Kaj Blennow

University of Gothenburg

Jan Lycke

University of Gothenburg

Mats Rudemo

University of Gothenburg

Chalmers, Mathematical Sciences, Mathematical Statistics

Bob Olsson

University of Gothenburg

Multiple Sclerosis

1352-4585 (ISSN) 1477-0970 (eISSN)

Vol. 19 4 403-410

Subject Categories

Radiology, Nuclear Medicine and Medical Imaging





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