Virome capture sequencing does not identify active viral infection in unicentric and idiopathic multicentric Castleman disease

Autor: David C. Fajgenbaum, Stephen Sameroff, Signe Spetalen, Mitsuhiro Kawano, Michael Feldman, Daisy Alapat, Amy Chadburn, Jason R. Ruth, Dustin Shilling, Katie L. Stone, Federico Valdivieso, Alexander Fosså, Frits van Rhee, Christopher S. Nabel, Yasuharu Sato, W. Ian Lipkin
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
RNA viruses
Male
Pathology
Epstein-Barr Virus Infections
Herpesvirus 4
Human
viruses
030204 cardiovascular system & hematology
medicine.disease_cause
Pathology and Laboratory Medicine
Hematologic Cancers and Related Disorders
0302 clinical medicine
Medicine and Health Sciences
T-cell lymphoma
Lymph node
False Negative Reactions
Multidisciplinary
Castleman disease
virus diseases
Hematology
Herpesviridae Infections
Middle Aged
medicine.anatomical_structure
Oncology
Medical Microbiology
Virus Diseases
Viral Pathogens
Viruses
Herpesvirus 8
Human
Medicine
Lymphomas
Female
Anatomy
Pathogens
Research Article
Adult
medicine.medical_specialty
Herpesviruses
Hepatitis B virus
Science
Histopathology
Genome
Viral
Microbiology
Herpesviridae
Virus
Lymphatic System
03 medical and health sciences
dsRNA viruses
medicine
Epstein-Barr virus
Humans
Human virome
Microbial Pathogens
Aged
business.industry
Castleman Disease
Organisms
Biology and Life Sciences
Cancers and Neoplasms
medicine.disease
Epstein–Barr virus
Hepatitis viruses
Lymphoma
030104 developmental biology
Anatomical Pathology
Case-Control Studies
DNA
Viral
Lymph Nodes
business
DNA viruses
Zdroj: PLoS ONE, Vol 14, Iss 6, p e0218660 (2019)
PLoS ONE
ISSN: 1932-6203
Popis: Castleman disease (CD) describes a spectrum of heterogeneous disorders defined by characteristic lymph node histopathology. Enlarged lymph nodes demonstrating CD histopathology can occur in isolation (unicentric CD; UCD) sometimes accompanied by mild symptoms, or at multiple sites (multicentric CD, MCD) with systemic inflammation and cytokine-driven multi-organ dysfunction. The discovery that Kaposi sarcoma herpesvirus/human herpesvirus (HHV)-8 drives MCD in a subset of patients has led to the hypotheses that UCD and MCD patients with negative HHV-8 testing by conventional methods may represent false negatives, or that these cases are driven by another virus, known or unknown. To investigate these hypotheses, the virome capture sequencing for vertebrate viruses (VirCapSeq-VERT) platform was employed to detect RNA transcripts from known and novel viruses in fresh frozen lymph node tissue from CD patients (12 UCD, 11 HHV-8-negative MCD [idiopathic MCD; iMCD], and two HHV-8-positive MCD) and related diseases (three T cell lymphoma and three Hodgkin lymphoma). This assay detected HHV-8 in both HHV-8-positive cases; however, HHV-8 was not found in clinically HHV-8-negative iMCD or UCD cases. Additionally, no novel viruses were discovered, and no single known virus was detected with apparent association to HHV-8-negative CD cases. Herpesviridae family members, notably including Epstein-Barr virus (EBV), were detected in 7 out of 12 UCD and 5 of 11 iMCD cases with apparent correlations with markers of disease severity in iMCD. Analysis of a separate cohort of archival formalin-fixed, paraffin-embedded lymph node tissue by In situ hybridization revealed significantly fewer EBV-positive cells in UCD and iMCD compared to tissue from HHV-8-positive MCD and EBV-associated lymphoproliferative disorder. In an additional cohort, quantitative testing for EBV by PCR in peripheral blood during disease flare did not detect systemic EBV viremia, suggesting detection lymph node tissue is due to occult, local reactivation in UCD and iMCD. This study confirms that HHV-8 is not present in UCD and iMCD patients. Further, it fails to establish a clear association between any single virus, novel or known, and CD in HHV-8-negative cases. Given that distinct forms of CD exist with viral and non-viral etiological drivers, CD should be considered a group of distinct and separate diseases with heterogeneous causes worthy of further study.
Databáze: OpenAIRE
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