Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from patients with Langerhans cell histiocytosis

Ichiro Murakami, Michiko Matsushita, Takeshi Iwasaki, Satoshi Kuwamoto, Masako Kato, Yasushi Horie, Kazuhiko Hayashi, Toshihiko Imamura, Akira Morimoto, Shinsaku Imashuku, Jean Gogusev, Francis Jaubert, Katsuyoshi Takata, Takashi Oka, Tadashi Yoshino

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Summary Langerhans cell histiocytosis (LCH) is a group of granulomatous disorders in which abnormal Langerhans cells proliferate as either a localized lesion in a single bone or disseminated disease involving two or more organs or systems. Because the different LCH forms exhibit significantly elevated levels of inflammatory molecules, including pro-inflammatory cytokines and tissue-degrading enzymes, we investigated for a possible viral trigger in LCH pathogenesis. We looked for Merkel cell polyomavirus (MCPyV) in peripheral blood cells and tissues using quantitative real-time PCR and immunohistochemistry staining with anti-MCPyV large T-antigen antibody. Our findings revealed elevated amounts of MCPyV DNA in the peripheral blood cells of 2 of 3 patients affected by LCH with high-risk organ involvement (RO+) and absence of MCPyV DNA in the blood cells in all 12 LCH-RO- patients (P =.029). With lower viral loads (0.002-0.033 copies/cell), an elevated number of MCPyV DNA sequences was detected in 12 LCH tissues in comparison with control tissues obtained from patients with reactive lymphoid hyperplasia (0/5; P =.0007), skin diseases not related to LCH in children younger than 2 years (0/11; P =.0007), or dermatopathic lymphadenopathy (5/20; P =.0002). The data, including frequent but lower viral loads and low large-T antigen expression rate (2/13 LCH tissues), suggest that development of LCH as a reactive rather than a neoplastic process may be related to MCPyV infection.

Original languageEnglish
Pages (from-to)119-126
Number of pages8
JournalHuman Pathology
Volume45
Issue number1
DOIs
Publication statusPublished - Jan 2014

Fingerprint

Merkel cell polyomavirus
Langerhans Cell Histiocytosis
Blood Cells
Viral Load
Polyomavirus Infections
Pseudolymphoma
Polyomavirus Transforming Antigens
Neoplastic Processes
Langerhans Cells
Viral Tumor Antigens
DNA
Skin Diseases
Real-Time Polymerase Chain Reaction
Cell Count
Immunohistochemistry

Keywords

  • Dermatopathic lymphadenopathy
  • Langerhans cell histiocytosis
  • Langerhans cells
  • Merkel cell polyomavirus
  • Multiplex quantitative real-time PCR

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from patients with Langerhans cell histiocytosis. / Murakami, Ichiro; Matsushita, Michiko; Iwasaki, Takeshi; Kuwamoto, Satoshi; Kato, Masako; Horie, Yasushi; Hayashi, Kazuhiko; Imamura, Toshihiko; Morimoto, Akira; Imashuku, Shinsaku; Gogusev, Jean; Jaubert, Francis; Takata, Katsuyoshi; Oka, Takashi; Yoshino, Tadashi.

In: Human Pathology, Vol. 45, No. 1, 01.2014, p. 119-126.

Research output: Contribution to journalArticle

Murakami, I, Matsushita, M, Iwasaki, T, Kuwamoto, S, Kato, M, Horie, Y, Hayashi, K, Imamura, T, Morimoto, A, Imashuku, S, Gogusev, J, Jaubert, F, Takata, K, Oka, T & Yoshino, T 2014, 'Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from patients with Langerhans cell histiocytosis', Human Pathology, vol. 45, no. 1, pp. 119-126. https://doi.org/10.1016/j.humpath.2013.05.028
Murakami, Ichiro ; Matsushita, Michiko ; Iwasaki, Takeshi ; Kuwamoto, Satoshi ; Kato, Masako ; Horie, Yasushi ; Hayashi, Kazuhiko ; Imamura, Toshihiko ; Morimoto, Akira ; Imashuku, Shinsaku ; Gogusev, Jean ; Jaubert, Francis ; Takata, Katsuyoshi ; Oka, Takashi ; Yoshino, Tadashi. / Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from patients with Langerhans cell histiocytosis. In: Human Pathology. 2014 ; Vol. 45, No. 1. pp. 119-126.
@article{70992e277ad141d9ab135b405bb30588,
title = "Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from patients with Langerhans cell histiocytosis",
abstract = "Summary Langerhans cell histiocytosis (LCH) is a group of granulomatous disorders in which abnormal Langerhans cells proliferate as either a localized lesion in a single bone or disseminated disease involving two or more organs or systems. Because the different LCH forms exhibit significantly elevated levels of inflammatory molecules, including pro-inflammatory cytokines and tissue-degrading enzymes, we investigated for a possible viral trigger in LCH pathogenesis. We looked for Merkel cell polyomavirus (MCPyV) in peripheral blood cells and tissues using quantitative real-time PCR and immunohistochemistry staining with anti-MCPyV large T-antigen antibody. Our findings revealed elevated amounts of MCPyV DNA in the peripheral blood cells of 2 of 3 patients affected by LCH with high-risk organ involvement (RO+) and absence of MCPyV DNA in the blood cells in all 12 LCH-RO- patients (P =.029). With lower viral loads (0.002-0.033 copies/cell), an elevated number of MCPyV DNA sequences was detected in 12 LCH tissues in comparison with control tissues obtained from patients with reactive lymphoid hyperplasia (0/5; P =.0007), skin diseases not related to LCH in children younger than 2 years (0/11; P =.0007), or dermatopathic lymphadenopathy (5/20; P =.0002). The data, including frequent but lower viral loads and low large-T antigen expression rate (2/13 LCH tissues), suggest that development of LCH as a reactive rather than a neoplastic process may be related to MCPyV infection.",
keywords = "Dermatopathic lymphadenopathy, Langerhans cell histiocytosis, Langerhans cells, Merkel cell polyomavirus, Multiplex quantitative real-time PCR",
author = "Ichiro Murakami and Michiko Matsushita and Takeshi Iwasaki and Satoshi Kuwamoto and Masako Kato and Yasushi Horie and Kazuhiko Hayashi and Toshihiko Imamura and Akira Morimoto and Shinsaku Imashuku and Jean Gogusev and Francis Jaubert and Katsuyoshi Takata and Takashi Oka and Tadashi Yoshino",
year = "2014",
month = "1",
doi = "10.1016/j.humpath.2013.05.028",
language = "English",
volume = "45",
pages = "119--126",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",
number = "1",

}

TY - JOUR

T1 - Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from patients with Langerhans cell histiocytosis

AU - Murakami, Ichiro

AU - Matsushita, Michiko

AU - Iwasaki, Takeshi

AU - Kuwamoto, Satoshi

AU - Kato, Masako

AU - Horie, Yasushi

AU - Hayashi, Kazuhiko

AU - Imamura, Toshihiko

AU - Morimoto, Akira

AU - Imashuku, Shinsaku

AU - Gogusev, Jean

AU - Jaubert, Francis

AU - Takata, Katsuyoshi

AU - Oka, Takashi

AU - Yoshino, Tadashi

PY - 2014/1

Y1 - 2014/1

N2 - Summary Langerhans cell histiocytosis (LCH) is a group of granulomatous disorders in which abnormal Langerhans cells proliferate as either a localized lesion in a single bone or disseminated disease involving two or more organs or systems. Because the different LCH forms exhibit significantly elevated levels of inflammatory molecules, including pro-inflammatory cytokines and tissue-degrading enzymes, we investigated for a possible viral trigger in LCH pathogenesis. We looked for Merkel cell polyomavirus (MCPyV) in peripheral blood cells and tissues using quantitative real-time PCR and immunohistochemistry staining with anti-MCPyV large T-antigen antibody. Our findings revealed elevated amounts of MCPyV DNA in the peripheral blood cells of 2 of 3 patients affected by LCH with high-risk organ involvement (RO+) and absence of MCPyV DNA in the blood cells in all 12 LCH-RO- patients (P =.029). With lower viral loads (0.002-0.033 copies/cell), an elevated number of MCPyV DNA sequences was detected in 12 LCH tissues in comparison with control tissues obtained from patients with reactive lymphoid hyperplasia (0/5; P =.0007), skin diseases not related to LCH in children younger than 2 years (0/11; P =.0007), or dermatopathic lymphadenopathy (5/20; P =.0002). The data, including frequent but lower viral loads and low large-T antigen expression rate (2/13 LCH tissues), suggest that development of LCH as a reactive rather than a neoplastic process may be related to MCPyV infection.

AB - Summary Langerhans cell histiocytosis (LCH) is a group of granulomatous disorders in which abnormal Langerhans cells proliferate as either a localized lesion in a single bone or disseminated disease involving two or more organs or systems. Because the different LCH forms exhibit significantly elevated levels of inflammatory molecules, including pro-inflammatory cytokines and tissue-degrading enzymes, we investigated for a possible viral trigger in LCH pathogenesis. We looked for Merkel cell polyomavirus (MCPyV) in peripheral blood cells and tissues using quantitative real-time PCR and immunohistochemistry staining with anti-MCPyV large T-antigen antibody. Our findings revealed elevated amounts of MCPyV DNA in the peripheral blood cells of 2 of 3 patients affected by LCH with high-risk organ involvement (RO+) and absence of MCPyV DNA in the blood cells in all 12 LCH-RO- patients (P =.029). With lower viral loads (0.002-0.033 copies/cell), an elevated number of MCPyV DNA sequences was detected in 12 LCH tissues in comparison with control tissues obtained from patients with reactive lymphoid hyperplasia (0/5; P =.0007), skin diseases not related to LCH in children younger than 2 years (0/11; P =.0007), or dermatopathic lymphadenopathy (5/20; P =.0002). The data, including frequent but lower viral loads and low large-T antigen expression rate (2/13 LCH tissues), suggest that development of LCH as a reactive rather than a neoplastic process may be related to MCPyV infection.

KW - Dermatopathic lymphadenopathy

KW - Langerhans cell histiocytosis

KW - Langerhans cells

KW - Merkel cell polyomavirus

KW - Multiplex quantitative real-time PCR

UR - http://www.scopus.com/inward/record.url?scp=84890071984&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890071984&partnerID=8YFLogxK

U2 - 10.1016/j.humpath.2013.05.028

DO - 10.1016/j.humpath.2013.05.028

M3 - Article

C2 - 24321520

AN - SCOPUS:84890071984

VL - 45

SP - 119

EP - 126

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

IS - 1

ER -