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Global transcriptome profiling of mild relapsing‐remitting versus primary progressive multiple sclerosis
Author(s) -
Koch M. W.,
Ilnytskyy Y.,
Golubov A.,
Metz L. M.,
Yong V. W.,
Kovalchuk O.
Publication year - 2018
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13565
Subject(s) - transcriptome , multiple sclerosis , gene expression , gene , phenotype , gene expression profiling , medicine , fold change , antigen processing , immunology , biological pathway , immune system , chemokine , biology , genetics , antigen presentation , t cell
Background and purpose Genetic research in multiple sclerosis ( MS ) mostly compares patients with MS with healthy controls, but does not differentiate between MS disease courses. We compared peripheral blood gene expression patterns between extremes of MS phenotypes, i.e. patients with mild relapsing‐remitting MS ( mRRMS ) and primary progressive MS ( PPMS ). Methods We analyzed global gene expression profiles of peripheral blood samples of age‐ and gender‐matched patients with mRRMS and PPMS . Detailed bioinformatic and gene set enrichment analysis, pathway and principle component analyses were used to identify differentially expressed genes and pathways. Results A total of 84 genes were significantly deregulated between the groups. Of those, 19 had been previously reported to be deregulated in patients with MS as compared with healthy controls, including major histocompatibility complex, interferon receptor 2 and interleukin 6 receptor. Detailed molecular pathway analysis revealed significant up‐regulation of antigen processing and presentation, leukocyte transendothelial migration, nucleotide‐binding oligomerization domain‐like receptor signaling, chemokine signaling and down‐regulation of RNA transport, spliceosome and aminoacyl‐ tRNA biosynthesis pathways in PPMS compared with mRRMS . Conclusion Our analyses show significant differences between mRRMS and PPMS gene expression. Surprisingly, the differentially expressed genes were mostly involved in immunological and inflammatory pathways, suggesting that the difference in MS phenotypes is caused primarily by a difference in immune responses. It should be kept in mind that our analyses were in peripheral blood only, and that the observed differences in inflammatory pathways may be a substrate of the analysed tissue. Further research into gene expression differences between disease courses including analyses in central nervous system tissue is warranted.

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