Using ANOVA to analyse thalidomide’s molecular mechanisms in human PBMC microarrays

Thalidomide is an anti-inflammatory and immunomodulatory drug that is the treatment of choice for erythema nodosum leprosum (ENL), an inflammatory cutaneous and systemic complication of multibacillary leprosy. Its use in leprosy and other conditions is controversial due to its teratogenic effects. Fifty years after the development of thalidomide, its action mechanism is still not well understood. In the present study we analyzed the in vitro effect of thalidomide on global gene expression in cultured human Peripheral Blood Mononuclear Cells (PBMC) of normal donors. We normalized the background subtracted spotted cDNA microarray data using a locally weighted linear regression and modeled its residual by a two-step analysis of variance to detect differentially expressed PBMC human genes in response to thalidomide. Using the full set of spotted genes, 13 genes were identified as differentially expressed genes. A reduced set was derived with a direct simple filtering approach and this set resulted in eight differentially expressed genes. Among these 21 genes, 15 are involved in the immune regulation processes.