Inflammatory responses are orchestrated by a complex network of cells and mediators, including circulating proteins such as cytokines and soluble receptors. The development of high-throughput proteomic technologies now allows for profiling of the plasma proteome at scale. Studying the proteome is valuable from both a basic and translational perspective since proteins are the effector molecules of biology and the targets of most drugs.
In the first half of this talk I will outline our work using various proteomic platforms in clinical cohorts to profile immune-mediated diseases, focussing on lupus and vasculitis.
In the second half of the talk, I will describe our proteo-genomic studies in epidemiological scale cohorts, identifying genetic variants associated with protein abundance (pQTLs). I will describe how pQTLs can be integrated with GWAS data to provide insights into the molecular basis of complex diseases by identifying proteins that lie between genotype and phenotype. In particular, I will focus on the use of techniques such as Mendelian randomisation analysis which allow us to move beyond descriptive molecular data to identifying proteins likely to play a causal role in immune-mediated disease etiology.