Ricerc@Sapienza

Background: Myocarditis is an inflammatory disease of myocardium that frequently lead to heart failure as results of an immune mediated cardiac damage. Toll-like receptor (TLR)-4, a molecular component that regulates the innate immune system, plays an important role in the induction and perpetuation of inflammation in autoimmune diseases. We recently demonstrated that myocardial expression of TLR-4 is increased in autoimmune myocarditis and can predict the response to immunosuppression.
Aim of the present study is to determine whether TLR-4 expression on PBMC of patients with autoimmune myocarditis is a biomarker to identify patients who will benefit from immunosuppressive therapy and to predict the resolution or recurrence of the myocardial inflammatory disease at follow-up.
Methods: In our center from January 2016 to January 2018 45 patients with histological and molecular diagnosis of virus negative inflammatory cardiomyopathy were treated for six-months with immunosuppression. PBMC isolated from whole blood at the time of the baseline endomyocardial biopsy will be examined for the expression of TLR4, differentiating those patients responding to immunosuppression with non-responder patients. A semiquantitative evaluation of the myocardial immunoreactivity (grading from 0 to 4) for TLR4 at baseline will be performed and correlated with the protein expression on PBMC. All patients will be submitted to a clinical follow-up, including a cardiac magnetic resonance. Follow-up PBMC assessment of TLR-4 will be also performed to evaluate if TLR-4 upregulation can be reverted within normal limits in parallel with improvement in cardiac dimension and function.
Expected results: The expected result of this project is to validate TLR-4 expression on PBMC as a reliable biomarker to guide the prompt instauration of immunosuppressive therapy in virus-negative myocarditis, with an improvement in patients prognosis.