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Characterization of plasmacytoid and myeloid dendritic cells in acute human and experimental myocarditis

Session Comorbidities and cardiomyopathies - How to manage?

Speaker Rudin Pistulli

Event : Heart Failure 2018

  • Topic : valvular, myocardial, pericardial, pulmonary, congenital heart disease
  • Sub-topic : Myocarditis
  • Session type : Rapid Fire Abstracts

Authors : R Pistulli (Jena,DE), E Andreas (Jena,DE), S Koenig (Leipzig,DE), S Drobnik (Jena,DE), D Kretzschmar (Jena,DE), M Lichtenauer (Salzburg,AT), B Heidecker (Zurich,CH), M Franz (Jena,DE), G Mall (Jena,DE), A Yilmaz (schmalkalden,DE), P C Schulze (Jena,DE)

Authors:
R Pistulli1 , E Andreas2 , S Koenig3 , S Drobnik4 , D Kretzschmar1 , M Lichtenauer5 , B Heidecker6 , M Franz1 , G Mall4 , A Yilmaz7 , P C Schulze1 , 1University Hospital of Jena, Internal Medicine I, Dept. of Cardiology - Jena - Germany , 2University Hospital of Jena, Department of Anesthesiology - Jena - Germany , 3Heart Center of Leipzig, Cardiac Electrophysiology - Leipzig - Germany , 4University Hospital of Jena, Department of Forensic Science - Jena - Germany , 5Paracelsus Private Medical University, Cardiology - Salzburg - Austria , 6University Heart Center, Cardiology - Zurich - Switzerland , 7Elisabeth-Hospital, Clinic of Internal Medicine II - schmalkalden - Germany ,

Citation:

AIMS: Dendritic cells (DCs) are central mediators of adaptive immunity but their role in human myocardial inflammatory disease is still unknown. We hypothesized that plasmacytoid (p) and myeloid (m) DCs are involved in the mechanisms of myocarditis and analyzed these two main subtypes in human myocarditis subjects as well as in a murine model of experimental autoimmune myocarditis (EAM).

METHODS: Circulating DCs were analyzed by flow cytometry (FACS) in patients with acute myocarditis (n=33), dilated cardiomyopathy (DCM, n=33) and controls (n=33) at initial diagnosis and at follow-up at 6 and 12 months. Myocardial biopsies of acute myocarditis patients (n = 18) were immunostained for the presence of DCs and compared to non-diseased controls (n=5). In a mouse model of acute myocarditis induced through synthetic cardiac myosine injection, effects of DC inhibition through MCS-18 treatment and placebo were tested. Histology, immunohistochemistry and echocardiography were performed at 21 days (peak myocarditis) and 28 days (recovery phase) following EAM induction.

RESULTS: Circulatory pDCs and mDCs were significantly reduced in myocarditis patients (p<0.01 for both), increased at 6 months follow-up, yet remained reduced compared to controls (pDCs p=0.015, mDCs p=0.002). Circulatory DCs of DCM patients were initially indifferent, but gradually decreased during follow-up, reaching significant reduction at 6 (mDCs, p 0.03) or at 12 months (pDCs, p<0.01) follow-up. Human myocarditis biopsies showed accumulation of pDCs (2-fold CD304+ / 3-fold CD123+, all p<0.01) compared to controls. Myocardial pDCs and mDCs accumulated in EAM (p for both <0.0001). MCS-18 Inhibition reduction pDC levels (p=0.009), reduced myocardial inflammation (myocarditis score reduction from 2.6 to 1.8, p=0.026) and improved ejection fraction (p=0.03) at peak myocarditis.

CONCLUSIONS: Circulating DCs are reduced in human myocarditis and accumulate in the inflamed myocardium. MCS-18 inhibits DCs in EAM leading to amelioration of inflammation and LV remodeling during the acute phase of myocarditis. Our data further elucidate the role of DCs and their specific subsets in acute inflammatory cardiomyopathies.

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