Our project aims to define biomarkers of severe primary ITP and identify genetic susceptibility loci implicated in loss of self-tolerance. This study builds directly on the promising results of our AKC grant #2052 “Immunoprofiling Canine ITP for Individualized Therapy.” Our preliminary genome wide association study (GWAS) revealed a novel ITP trait locus on CFA1. Our first objective is to complete the GWAS with newly accrued ITP cases in a prospective, multi-institutional cohort study. These analyses will determine whether CD226, a candidate disease gene within the trait locus, plays a role in ITP pathogenesis and allow us to determine whether CD226 polymorphisms influence the number or function of immunomodulatory T regulatory (Treg) cells.
Our second objective is to identify ITP severity predictors. We will further evaluate laboratory parameters previously associated with poor clinical outcomes, including aberrant platelet membrane CD61 expression and high circulating C-reactive protein (CRP), and confirm diagnostic utility of our newly developed DOGiBAT clinical bleeding score. Defining severity predictors will enable a novel paradigm of calibrated ITP therapy, guiding clinicians to match treatment intensity with disease activity. Together, our genotyping and phenotyping strategy will lead to individualized, targeted patient management.