期刊
CLINICAL INFECTIOUS DISEASES
卷 -, 期 -, 页码 -出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciad237
关键词
Aichi virus; chronic hepatitis; metagenomic next-generation sequencing; X-linked agammaglobulinemia; primary immune deficiency
Using metagenomic next-generation sequencing and reverse-transcription polymerase chain reaction, we detected the Aichi virus genome in tissues of patients with primary immune deficiency and unexplained multiorgan inflammatory involvement. We showed evidence supporting the causality of Aichi virus in these cases.
Using metagenomic next-generation sequencing and reverse-transcription polymerase chain reaction, we detected the Aichi virus genome in tissues of patients with primary immune deficiency and unexplained multiorgan inflammatory involvement. We showed evidence supporting the causality of Aichi virus in these cases. Background Metagenomic next-generation sequencing (mNGS) was used to assess patients with primary or secondary immune deficiencies (PIDs and SIDs) who presented with immunopathological conditions related to immunodysregulation. Methods Thirty patients with PIDs or SIDs who presented with symptoms related to immunodysregulation and 59 asymptomatic patients with similar PIDs or SIDs were enrolled. mNGS was performed on organ biopsy. Specific Aichi virus (AiV) reverse-transcription polymerase chain reaction (RT-PCR) was used to confirm AiV infection and screen the other patients. In situ hybridization (ISH) assay was done on AiV-infected organs to identify infected cells. Virus genotype was determined by phylogenetic analysis. Results AiV sequences were detected using mNGS in tissue samples of 5 patients and by RT-PCR in peripheral samples of another patient, all of whom presented with PID and long-lasting multiorgan involvement, including hepatitis, splenomegaly, and nephritis in 4 patients. CD8+ T-cell infiltration was a hallmark of the disease. RT-PCR detected intermittent low viral loads in urine and plasma from infected patients but not from uninfected patients. Viral detection stopped after immune reconstitution obtained by hematopoietic stem cell transplantation. ISH demonstrated the presence of AiV RNA in hepatocytes (n = 1) and spleen tissue (n = 2). AiV belonged to genotype A (n = 2) or B (n = 3). Conclusions The similarity of the clinical presentation, the detection of AiV in a subgroup of patients suffering from immunodysregulation, the absence of AiV in asymptomatic patients, the detection of viral genome in infected organs by ISH, and the reversibility of symptoms after treatment argue for AiV causality.
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