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Advances in the immunohistological diagnosis of inflammatory cardiomyopathy

M. Noutsias*, M. Pauschinger, H.-P. Schultheiss and U. Kühl

Department of Cardiology and Pneumonology, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Germany

* Correspondence: Michel Noutsias, Department of Cardiology and Pneumonology, University Hospital Benjamin Franklin, Free University of Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany.

Abstract

Dilated cardiomyopathy (DCM) is aetiopathogenically linked to intra-myocardial inflammation, which is most often evoked by cardiotropic viral (coxsackieviral and adenoviral) infection. Diagnosis of inflammatory cardiomyopathy (InfCM) imposes sensitivity and specificity requirements that are not fulfilled by the histological Dallas criteria because of considerable inter-observer variability and sampling error. Quantitative immunohistological evaluation of endo-myocardial biopsies consistently confirmed the presence of InfCM in approximately 50% of the DCM patients. In this context, T-lymphocytic infiltrates, macrophages and endothelial cellular adhesion molecule expression emerged as diagnostic hallmarks of InfCM. The close association between immunocompetent infiltrates and endothelial cellular adhesion molecule abundance confirmed the hypothesized inter-dependence of those factors. The homogenous cellular adhesion molecule expression pattern infers a negligible sampling error associated with immunohistological diagnosis of InfCM. Phenotypic characterization of infiltrates revealed that, in addition to the mean infiltration number of T lymphocytes (>7·0 cells. mm–2), activated and specifically cytotoxic lymphocytes, as well as macrophages, deserve attention in the diagnosis of InfCM. These insights were confirmed by automated digital image analysis, which enables a standardized quantification mode that is devoid of inter-observer variability. Several trials confirmed that, in contrast to the conventional Dallas criteria, the immunohistological InfCM criteria are valid for the selection of DCM patients who will benefit from immunosuppressive treatment. In the post-Dallas-criteria era, immunohistological evaluation of endo-myocardial biopsies may eventually guide immunomodulatory treatment of patients with InfCM.

Key Words: Adhesion molecules • diagnosis • dilated cardiomyopathy • immunohistology • immune system • infiltrates • inflammatory cardiomyopathy • phenotypic characterization

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