Toll-like receptor 4 is a marker of immune-mediated damage in patients with inflammatory cardiomyopathy

Abstract

Purpose: Toll-like receptor 4 has been involved in the development of experimental autoimmune myocarditis. The aim of the study is to determine whether Toll-like receptor 4 plays a role in human myocarditis responsive to immunosuppression. Methods: Left ventricular endomyocardial biopsies from a subgroup of patients from the TIMIC trial were analyzed for the immunohistochemical expression of Toll-like receptor 4. In particular 18 patients (8 males,16 females, age 48.6±12.1 ys) with chronic (>6 months), virus negative (negative PCR for EV, AV, EBV, PVB19, HCV, Inf A/B, HSV1/2) inflammatory cardiomyopathy (LVEF 29.4±7.3%), responders to a 6 months treatment with prednisone and azathioprine were studied (group A). Controls were 10 left ventricular biopsies of patients with virus-negative inflammatory cardiomyopathy not responders to immunosuppression (group B) and 10 normal left ventricular surgical samples (group C). A semiquantitative evaluation of the immunoreactivity (grading from 0 to 4) was applied. Results: A focal intense positive cytoplasmic immunoreactivity was observed in cardiac myocytes of all patients in group A (grading 3.5±0.5) (panel A), with a statistically significant difference (p<0.001) compared with group B (grading 0.8±0.4) (panel B) and controls (0.2±0.4) (panel C). ![Figure][1] Conclusion: Toll-like receptor 4 is highly expressed in human immune-mediated myocarditis. It can be considered as a new marker in patient selection for immunosuppressive/immunomodulatory therapy. [1]: pending:yes