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Chronic Aichi virus infection as a cause of long-lasting multi-organ involvement in patients with primary immune deficiencies
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Edité par CCSD ; Oxford University Press (OUP) -
International audience. BackgroundMetagenomic Next Generation Sequencing (mNGS) was used to assess patients with primary or secondary Immune Deficiencies (PIDs and SIDs) presenting with immunopathological conditions related to immunodysregulation.Methods30 patients with PIDs and SIDs presenting symptoms related to immunodysregulation and 59 asymptomatic patients with similar PIDs and SIDs were enrolled. mNGS was performed on organ biopsy. Specific AiV RT-PCR was used to confirm Aichi virus (AiV) infection and screen the other subjects. In situ hybridization assay (ISH) was done on AiV infected organs to identify infected cells. Virus genotype was determined by phylogenetic analysis.ResultsAiV sequences were detected by mNGS in tissue samples of 5 patients and by RT-PCR in peripheral samples of another patient who all presented with PID and long-lasting multi-organ involvement, including hepatitis, splenomegaly and nephritis in 4. 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 in none of the other subjects. Viral detection stopped after immune reconstitution obtained by hematopoietic stem cell transplantation. ISH demonstrated the presence of the AiV RNA in hepatocytes (n = 1) and spleen tissue (n = 2). AiV belonged to genotype A (n = 2) or B (n = 3).ConclusionsThe similarity of the clinical presentation, the detection of AiV in a sub-group of patients suffering from immunodysregulation, its absence 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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