Srinivasan Sundararajan, Di Dario Marco, Russo Alessandra, Menon Ramesh, Brini Elena, Romeo Marzia, Sangalli Francesca, Costa Gloria Dalla, Rodegher Mariaemma, Radaelli Marta, Moiola Lucia, Cantarella Daniela, Medico Enzo, Martino Gianvito, Furlan Roberto, Martinelli Vittorio, Comi Giancarlo, Farina Cinthia
Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
Neurol Neuroimmunol Neuroinflamm. 2017 Mar 16;4(3):e337. doi: 10.1212/NXI.0000000000000337. eCollection 2017 May.
To perform systematic transcriptomic analysis of multiple sclerosis (MS) risk genes in peripheral blood mononuclear cells (PBMCs) of subjects with distinct MS stages and describe the pathways characterized by dysregulated gene expressions.
We monitored gene expression levels in PBMCs from 3 independent cohorts for a total of 297 cases (including clinically isolated syndromes (CIS), relapsing-remitting MS, primary and secondary progressive MS) and 96 healthy controls by distinct microarray platforms and quantitative PCR. Differential expression and pathway analyses for distinct MS stages were defined and validated by literature mining.
Genes located in the vicinity of MS risk variants displayed altered expression in peripheral blood at distinct stages of MS compared with the healthy population. The frequency of dysregulation was significantly higher than expected in CIS and progressive forms of MS. Pathway analysis for each MS stage-specific gene list showed that dysregulated genes contributed to pathogenic processes with scientific evidence in MS.
Systematic gene expression analysis in PBMCs highlighted selective dysregulation of MS susceptibility genes playing a role in novel and well-known pathogenic pathways.
对不同多发性硬化（MS）阶段受试者的外周血单个核细胞（PBMC）中的MS风险基因进行系统的转录组分析，并描述以基因表达失调为特征的通路。
我们通过不同的微阵列平台和定量PCR监测了来自3个独立队列的297例患者（包括临床孤立综合征（CIS）、复发缓解型MS、原发进展型和继发进展型MS）以及96名健康对照的PBMC中的基因表达水平。通过文献挖掘定义并验证了不同MS阶段的差异表达和通路分析。
与健康人群相比，位于MS风险变异附近的基因在MS不同阶段的外周血中表达发生改变。在CIS和进展型MS中，失调频率显著高于预期。对每个MS阶段特异性基因列表的通路分析表明，失调基因在MS的致病过程中发挥作用且有科学依据。
PBMC中的系统基因表达分析突出了MS易感性基因的选择性失调在新的和已知致病通路中的作用。
