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 specificity 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(septic 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 samples 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-associated 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. Key words: Multiple sclerosis; Peripheral whole blood; Differentially expressed genes