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As shown in our recent paper (European Heart Journal 2021; 42(9):938–947), B cells are responsible for recurrent myocardial infarction (MI), by producing antibodies generated to tissues antigens released during MI. These antibodies accelerate the progression of atherosclerosis; accelerated atherosclerosis has been observed in humans after MI.

Our initial studies will focus on identifying pathogenic autoantibodies produced following MI in mice; studies will include molecular biology techniques — gene sequencing, gene cloning and protein expression in mammalian systems. Next, I will identify antigens from atherosclerotic lesions using immunological and proteomic technologies that utilise high-throughput mass spectrometry-based proteomics and bioinformatics. After identifying highly relevant mouse lesion antigens, equivalent human proteins will be cloned, expressed in mammalian cells and purified, enabling the development of ELISAs to detect autoantibodies in response to MI in humans.

We will also further develop approaches to more specifically prevent autoantibody generation after myocardial infarction. Specifically, we will develop smart, nanoparticles camouflaged as follicular CD4+ T cells by incorporating membranes isolated from follicular CD4+ T cells into nanoparticles; interactions between follicular T cells and B cells are critical for plasma cell formation and antibody generation. These nanoparticles will specifically prevent the formation of antibody-producing plasma cells in response to myocardial infarction without affecting global B cell responses by competing with follicular T cells for binding to follicular B cells in germinal centres. Nanoparticles will be characterised using electron microscopy and will be tested in animal models of MI/atherosclerosis and may lead to more specific therapies to prevent recurrent myocardial infarctions.

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