Pharmaceutical relevant cytokine receptors: lessons from the first drafts of the human proteome

Abstract

Although a plethora of human proteins are ubiquitously expressed, several proteins with high pharmaceutical relevance show a tissue- or cell-type specific expression pattern. Science across all disciplines, ranging from developmental biology to personalized medicine, would benefit from detailed knowledge about this so-called human proteome. Two recent publications in Nature use large-scale proteomics to create first drafts of the human proteome, which are freely accessible online. In this Letter, we analyze the proteomic data with regard to the expression of three different cytokine receptors, the Tumor Necrosis Factor (TNF)α Receptor I (TNFRSF1A) and II (TNFRSF1B) and the Interleukin-6 Receptor (IL-6R). Therapeutic inhibition of these proteins is highly effective in a high number of inflammatory diseases, and TNFα blocking agents alone were sold for almost $30 billion in 2013. We find that the known expression pattern of the three receptors is not reflected in the current drafts of the human proteome, as the proteomics data fail to detect protein expression in several cell types and tissues which are known to express these cytokine receptors. Thus, our results suggest that the current drafts of the human proteome are far from complete, and that the data have to be used with caution especially in terms of personalized medicine.

Keywords: human proteome; interleukin-6; proteome map; tumor necrosis factor.