title: Myocardial Immunocompetent Cells and Macrophage Phenotypes as Histopathological Surrogates for Diagnosis of Cardiac Sarcoidosis in Japanese.
abstract: The histological diagnosis of cardiac sarcoidosis (CS) is based on the presence of myocardial granulomas; however, the sensitivity of endomyocardial biopsy is relatively low. We investigated whether immunocompetent cells including dendritic cells (DC) and macrophages in nongranuloma sections of endomyocardial biopsy samples could be histopathological surrogates for CS diagnosis.
  
  
  
  The numbers of DC and macrophages were investigated in 95 consecutive CS patients and 50 patients with nonischemic cardiomyopathy as controls. All patients underwent endomyocardial biopsy, and immunohistochemical staining was performed on all samples. We examined these immunocompetent cells in nongranuloma sections in CS patients diagnosed by the presence of myocardial granulomas (n=26) and in CS patients without myocardial granulomas diagnosed by the Japanese Ministry of Health Welfare 2007 criteria (n=65) or the Heart Rhythm Society 2014 criteria (n=26). In CS patients with and without myocardial granulomas, CD209+DC and CD68+macrophages were more frequently observed (P<0.01) and CD163+M2 macrophages were less frequently observed (P<0.01) in nongranuloma sections compared to controls. Furthermore, the combination of decreased CD163+M2/CD68+macrophage ratio and increased number of CD209+DC in nongranuloma sections of CS patients demonstrated high specificity (100%, 95% CI 92.7-100) for CS diagnosis with each diagnostic criteria and the presence of myocardial granulomas.
  
  
  
  Increased number of DC and decreased M2 among all macrophages in nongranuloma sections of myocardium showed high specificity for CS diagnosis, suggesting DC and macrophage phenotypes as histopathological surrogates for the diagnosis of CS.
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Honda
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan nagai@ncvc.go.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Clinical Pathology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Sakakibara
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Asakawa
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Nagano
authors.affiliation: Department of Preventive Medicine and Epidemiology Informatics, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Michikazu
authors.initials: M
authors.lastname: Nakai
authors.affiliation: Department of Preventive Medicine and Epidemiology Informatics, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugano
authors.affiliation: Department of Clinical Pathology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohta-Ogo
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Asaumi
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aiba
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kanzaki
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kusano
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Noguchi
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
authors.affiliation: Department of Clinical Pathology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Hatsue
authors.initials: H
authors.lastname: Ishibashi-Ueda
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Anzai
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D044466:Asian People; D001706:Biopsy; D009202:Cardiomyopathies / Q000175:diagnosis / Q000276:immunology / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D007121:Immunocompetence; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007564:Japan; D037181:Lectins, C-Type / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000276:immunology; D012507:Sarcoidosis / Q000175:diagnosis / Q000276:immunology / Q000473:pathology*; D000098902:CD163 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: cardiac sarcoidosis; dendritic cell; diagnosis; diagnostic method; histopathology; inflammation; macrophage