Myocardial immunocompetent cells and macrophage phenotypes as histopathological surrogates for diagnosis of cardiac sarcoidosis in Japanese

Yasuyuki Honda, Toshiyuki Nagai, Yoshihiko Ikeda, Mamoru Sakakibara, Naoya Asakawa, Nobutaka Nagano, Michikazu Nakai, Kunihiro Nishimura, Yasuo Sugano, Keiko Ohta-Ogo, Yasuhide Asaumi, Takeshi Aiba, Hideaki Kanzaki, Kengo Kusano, Teruo Noguchi, Satoshi Yasuda, Hiroyuki Tsutsui, Hatsue Ishibashi-Ueda, Toshihisa Anzai

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Abstract

Background--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. Methods and Results--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. Conclusions--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.

Original languageEnglish
Article numbere004019
JournalJournal of the American Heart Association
Volume5
Issue number11
DOIs
Publication statusPublished - Nov 2016

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Sarcoidosis
Macrophages
Phenotype
Dendritic Cells
Granuloma
Biopsy
Cardiomyopathies
Myocardium
Staining and Labeling
Health

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Myocardial immunocompetent cells and macrophage phenotypes as histopathological surrogates for diagnosis of cardiac sarcoidosis in Japanese. / Honda, Yasuyuki; Nagai, Toshiyuki; Ikeda, Yoshihiko; Sakakibara, Mamoru; Asakawa, Naoya; Nagano, Nobutaka; Nakai, Michikazu; Nishimura, Kunihiro; Sugano, Yasuo; Ohta-Ogo, Keiko; Asaumi, Yasuhide; Aiba, Takeshi; Kanzaki, Hideaki; Kusano, Kengo; Noguchi, Teruo; Yasuda, Satoshi; Tsutsui, Hiroyuki; Ishibashi-Ueda, Hatsue; Anzai, Toshihisa.

In: Journal of the American Heart Association, Vol. 5, No. 11, e004019, 11.2016.

Research output: Contribution to journalArticle

Honda, Y, Nagai, T, Ikeda, Y, Sakakibara, M, Asakawa, N, Nagano, N, Nakai, M, Nishimura, K, Sugano, Y, Ohta-Ogo, K, Asaumi, Y, Aiba, T, Kanzaki, H, Kusano, K, Noguchi, T, Yasuda, S, Tsutsui, H, Ishibashi-Ueda, H & Anzai, T 2016, 'Myocardial immunocompetent cells and macrophage phenotypes as histopathological surrogates for diagnosis of cardiac sarcoidosis in Japanese', Journal of the American Heart Association, vol. 5, no. 11, e004019. https://doi.org/10.1161/JAHA.116.004019
Honda, Yasuyuki ; Nagai, Toshiyuki ; Ikeda, Yoshihiko ; Sakakibara, Mamoru ; Asakawa, Naoya ; Nagano, Nobutaka ; Nakai, Michikazu ; Nishimura, Kunihiro ; Sugano, Yasuo ; Ohta-Ogo, Keiko ; Asaumi, Yasuhide ; Aiba, Takeshi ; Kanzaki, Hideaki ; Kusano, Kengo ; Noguchi, Teruo ; Yasuda, Satoshi ; Tsutsui, Hiroyuki ; Ishibashi-Ueda, Hatsue ; Anzai, Toshihisa. / Myocardial immunocompetent cells and macrophage phenotypes as histopathological surrogates for diagnosis of cardiac sarcoidosis in Japanese. In: Journal of the American Heart Association. 2016 ; Vol. 5, No. 11.
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title = "Myocardial immunocompetent cells and macrophage phenotypes as histopathological surrogates for diagnosis of cardiac sarcoidosis in Japanese",
abstract = "Background--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. Methods and Results--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. Conclusions--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.",
author = "Yasuyuki Honda and Toshiyuki Nagai and Yoshihiko Ikeda and Mamoru Sakakibara and Naoya Asakawa and Nobutaka Nagano and Michikazu Nakai and Kunihiro Nishimura and Yasuo Sugano and Keiko Ohta-Ogo and Yasuhide Asaumi and Takeshi Aiba and Hideaki Kanzaki and Kengo Kusano and Teruo Noguchi and Satoshi Yasuda and Hiroyuki Tsutsui and Hatsue Ishibashi-Ueda and Toshihisa Anzai",
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T1 - Myocardial immunocompetent cells and macrophage phenotypes as histopathological surrogates for diagnosis of cardiac sarcoidosis in Japanese

AU - Honda, Yasuyuki

AU - Nagai, Toshiyuki

AU - Ikeda, Yoshihiko

AU - Sakakibara, Mamoru

AU - Asakawa, Naoya

AU - Nagano, Nobutaka

AU - Nakai, Michikazu

AU - Nishimura, Kunihiro

AU - Sugano, Yasuo

AU - Ohta-Ogo, Keiko

AU - Asaumi, Yasuhide

AU - Aiba, Takeshi

AU - Kanzaki, Hideaki

AU - Kusano, Kengo

AU - Noguchi, Teruo

AU - Yasuda, Satoshi

AU - Tsutsui, Hiroyuki

AU - Ishibashi-Ueda, Hatsue

AU - Anzai, Toshihisa

PY - 2016/11

Y1 - 2016/11

N2 - Background--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. Methods and Results--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. Conclusions--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.

AB - Background--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. Methods and Results--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. Conclusions--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.

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