Biopsy-proven myocarditis: peripheral immunophenotypes correlate with histology, etiology, immunosuppressive therapy

Le résumé fourni par la source

Myocarditis is an inflammatory disease of the myocardium with infectious or immune-mediated/autoimmune etiology; etiology diagnosis relays on endomyocardial biopsy (EMB). High titre serum anti-heart autoantibodies (AHA) define severe autoimmune forms. In autoimmune myocarditis immunosuppression (IS) may be required to prevent progression to dilated cardiomyopathy, heart transplant or death, but it is not always effective. This study aimed to identify non-invasive cellular biomarkers of etiology and response to IS in biopsy-proven myocarditis peripheral blood. Fifty-eight EMB-proven myocarditis patients out of IS were enrolled and compared with 9 healthy controls and 20 EMB-proven myocarditis on IS. Cells distribution was evaluated by flow cytometry; results were related to clinical, EMB and AHA findings. Compared to healthy controls, plasmacytoid dendritic cells percentage was reduced in autoimmune (p=0.017), in lymphocytic (p=0.012) myocarditis patients, in those without extra-cardiac autoimmune diseases (AD, p=0.01), and in myocarditis not on IS (p=0.003). Viral myocarditis had higher CD62L+/CD56+ NK cells percentage (p=0.001) and CCR2 over-expression in intermediate monocytes when compared with autoimmune myocarditis (p=0.013). Autoimmune myocarditis was characterized by higher Th1/Th2 (p=0.004) and Th17/Treg ratio (p=0.008), Th1 (p=0.028) and Th17 lymphocytes (p=0.017) percentage vs. healthy controls. A reduction of Treg cells percentage was specific for autoimmune lymphocytic (p=0.047 vs healthy controls), for AHA-positive myocarditis (p=0.03 vs healthy controls) and for myocarditis unresponsive to IS (p=0.036). Biopsy-proven myocarditis patients showed distinct peripheral immunophenotypes of either innate or adaptive immune cells according to different histology, etiology and response to IS, unveiling potential novel non-invasive etiological biomarkers for myocarditis. Graphic Abstract: Methods and key results are reported in the central illustration. CD: cluster of differentiation, CCR2: C-C motif chemokine receptor 2, IS: immunosuppression, NK: natural killer, pDC: plasmacytoid dendritic cell, Th: T helper, vs: versus. • Biopsy-proven (BP) myocarditis had peculiar peripheral immunophenotypes. • Patients were stratified for histology, etiology and response to immunosuppression. • Immune cells distribution varied among the different BP-myocarditis forms. • Peripheral blood immunophenotype may contribute to BP-myocarditis prognostic stratification.

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