B-specific · B-specific: B-cell related gene and protein markers with prognostic and therapeutic value for CVD

Atherosclerosis is the major underlying condition of cardiovascular disease (CVD) and one the leading causes of mortality. Rupture or erosion of atherosclerotic lesions can lead to acute cardiovascular events, such as myocardial infarction and stroke, making biomarkers to diagnose patients at risk for these events and develop tailored preventive interventions, an urgent need. Although atherosclerosis is a chronic inflammatory disease, clinical investigation of the adaptive immune system as a potential rheostat for disease development has been limited. The B-specific consortium aims to classify and mitigate risk of CVD by generating novel types of genetic data and defining novel prognostic and therapeutic targets attained from our recent discovery of a specific B-cell subset. We will employ state-of-the-art technology, including single cell RNA sequencing, BCR repertoire analysis and mass spectrometry-based identification of autoantigens in CVD patient material. With access to large population-based cohorts (FIMCOD, ERGO Study) spanning healthy adults of 40-105 years of age, we aim to assess the prognostic value of circulating B cell subsets and antibodies in (sub)clinical atherosclerosis and investigate the contribution of genetic disposition. Using the extensive genomics data of the ERGO Study, we will be able to determine causal links between the prognostic indicators and disease progression by applying Mendelian Randomization experiments and confirm these relationships in ex vivo and in vivo models of atherosclerosis. Based on these findings, B-specific aims to develop at least 1 proof-of-concept therapy targeting specific B cells. B-specific will implement an active open science platform and in combination with a targeted dissemination approach to healthcare professionals, we aim to impact cardiology practice and provide important new means of patient stratification and treatment options.