多发性硬化外周全血mRNA差异表达的来源及其特异性分析

目的 探究多发性硬化外周全血mRNA差异表达的来源及其特异性.方法 利用外周全血mRNA表达谱数据,分别筛选多发性硬化和炎症性疾病(感染性休克、肺结核)患者相对正常人群的差异表达基因并进行比较.筛选正常外周血中髓系相对淋巴系细胞的差异表达基因,并与多发性硬化患者相对正常人群的差异表达基因作比较.结果 比较多发性硬化患者与两种炎症性疾病(感染性休克、肺结核)患者相对正常人群的差异表达基因,发现交叠基因上/下调方向的一致性分别为91.32%(P<0.05),93.23%(P<0.05).比较多发性硬化患者相对正常人群的差异表达基因及正常人群髓系相对淋巴系细胞的差异表达基因,发现交叠基因上/下调方向的一致性为96.82%(P<0.05).结论 多发性硬化患者相对于正常人群的差异表达基因与炎症性疾病患者相对正常人群的差异表达基因高度一致,同时与髓系相对淋巴系细胞的差异表达基因同样高度一致.上述结果表明多发性硬化患者外周全血中观察到的基因表达的改变可能是由于髓系/淋巴系细胞构成比例改变所致,是非特异的炎症性改变.

Origin and specificity of differential expression genes in peripheral whole blood of multiple sclerosis

Objective A common approach to develop disease biomarkers for early detection and drug efficacy is to detect the differentially expressed(DE)genes of peripheral whole blood(PWB)between multiple sclerosis patients and normal population. However,DE genes between the two groups are likely due to the change of the proportion of myeloid / lymphoid cells in blood. Therefore,it is important to explore the origin and speci-ficity of DE genes in the PWB between multiple sclerosis(MS)patients and normal population. Methods First,using gene expression profiles of PWB samples from MS patients and inflammation-associated disease(sep-tic shock and tuberculosis)patients,we compared the DE genes between multiple sclerosis samples and healthy controls with the DE genes between inflammation-associated disease samples and healthy controls. Then,using gene expression profiles of myeloid cells and lymphoid cells from the PWB of normal population,we identified the DE genes between myeloid cells and lymphoid cells. Finally,we compared the DE genes between MS sam-ples and healthy controls with the DE genes between myeloid cells and lymphoid cells. Results The DE genes between MS samples and healthy controls were overlapped with the DE genes between other inflammation-associ-ated disease samples(septic shock and tuberculosis)and healthy controls. 91. 32%(P < 0. 05)and 93. 23%(P < 0. 05)of the overlapped genes had consistent directions of dysregulation(up- or down-regulations). The DE genes between MS and healthy controls were overlapped with the DE genes between myeloid cells and lymphoid cells,and 96. 82% of the overlapped genes had consistent directions of dysregulation(up- or down-regulations) (P < 0. 05). Conclusion The DE genes observed in PWB of MS were similar with the DE genes in PWB of other inflammation-associated diseases. This suggests that the changes of the expression profile in PWB of MS are nonspecific inflammatory changes. Furthermore,the DE genes detected in PWB of MS were similar with that between myeloid cells and lymphoid cells,which strongly demonstrates that changes of the expression profile in PWB of MS mainly reflect the shift in the proportion of immune cell subpopulations in PWB.