UCSF

Background

Adalimumab is an anti-TNF biologic drug that is efficacious in the treatment of psoriasis. However, the effect of adalimumab on genome-wide gene expression changes in skin and peripheral blood is not well characterized.

Methods

Thirty adult subjects with > 10% body surface area of chronic plaque psoriasis were recruited for the study. Lesional skin and peripheral blood mononuclear cell samples prior to and one month following treatment with adalimumab were collected. The skin samples were analyzed using genome-wide RNAseq, and the blood samples were analyzed using genome-wide Affymetrix microarrays. Data preprocessing and analysis were conducted using the EdgeR and Affy packages in R/Bioconductor.

Results

In the skin, paired analysis before and after treatment revealed changes in pathways important to epidermal development and keratinocyte differentiation. Such important genes as keratin 6A and 6B, tubulin B6, desmocollin, and desmoglein 3 were among the top differentially expressed genes. In peripheral blood, pathways involved in hematopoetic cell lineage and immune response were found to be differentially expressed, including genes such as the Fc receptor-like A and 5, as well as immunoglobulin heavy chains. Using a principal components approach, we show that expression of genes in post-treatment skin more closely resembles that of healthy controls.

Conclusion

Treatment of psoriasis with adalimumab appears to be associated with modulation of keratinocyte and epidermal proliferation in the skin and with immunologic changes in the blood. We discuss the ramifications of these findings for the treatment for psoriasis.

J Drugs Dermatol. 2016;15(8):988-994.