FBS Colloquia No.362Laboratory of Medical Biochemistry

Development of the novel therapeutic and diagnostic agents for fulminant lymphocytic myocarditis

Lymphocytic myocarditis is a diverse group of multiple heart-specific inflammatory conditions. Recently, the incidence rate of lymphocytic myocarditis is increasing as the complication of COVID-19 infection and the side-effect of Immuno-checkpoint inhibitors. Regardless of its etiology, the acute inflammation may progress to chronic stages and finally to dilated cardiomyopathy. Lymphocytic myocarditis still has high rates of cardiac death even under medical treatment. Therefore, in order to improve its prognosis, we aimed to detect new biomarkers and therapeutic targets for myocarditis.

As we found a specific pathological feature in the early stages of human myocarditis cases, in which activated fibroblasts proliferate and lymphocytes infiltrate in parallel. In the single cell RNA-seq analysis of myocarditis model, we identified the population of activated fibroblasts, which express the specific receptor recruiting lymphocytes into myocardium. Moreover, we also found that the inhibitor of the lymphocytic ligand against the receptor on fibroblasts reduced the inflammatory response in these model animals and improved the prognosis.

In addition, we developed a novel non-invasive diagnostic PET probe for myocarditis using this inhibitor by incorporating a PET nuclide (C11) into it. As expected, higher PET probe accumulation was observed in the myocardium of the myocarditis model. This PET probe is considered to be useful for spatial diagnosis of Lymphocytic Myocarditis because this signal makes it possible to quantify the amount of lymphocyte infiltration.