Lien vers Pubmed [PMID] – 36638922
Lien DOI – S0091-6749(23)00009-X10.1016/j.jaci.2022.12.822
J Allergy Clin Immunol 2023 Jan; ():
Allogenic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are potentially curative treatments for severe combined immunodeficiency (SCID). Late-onset post-treatment manifestations (such as persistent hepatitis) are not uncommon.To characterize the prevalence and pathophysiology of persistent hepatitis in transplanted SCID patients (SCIDH+) and to evaluate risk factors and treatments.We used a variety of techniques (including pathology assessments, metagenomics, single-cell transcriptomics, and cytometry by time of flight) to perform an in-depth study of different tissues from SCIDH+ patients and corresponding asymptomatic similarly transplanted SCID patients (without hepatitis, SCIDH-).Eleven patients developed persistent hepatitis (median of 6 years after HSCT or GT). This condition was associated with the chronic detection of enteric viruses (human Aichi virus, norovirus and sapovirus) in liver and/or stools, which were not found in stools SCIDH- (n=12). Multi-omics analysis identified an expansion of effector memory CD8+ T cells with a high type I and II interferon signatures. Hepatitis was associated with absence of myeloablation during conditioning, split chimerism and defective B cell function, representing 25% of the 44 SCID patients having these characteristics. Partially myeloablative re-transplantation or GT of patients with this condition (which we have named “enteric virus infection associated with hepatitis” (EVAH)) led to the reconstitution of T and B cell immunity and remission of hepatitis, concomitantly to viral clearance in 5 patients.EVAH is associated with chronic enteric viral infection and immune dysregulation and is an important risk for transplanted SCID patients with defective B cell function.
https://pubmed.ncbi.nlm.nih.gov/36638922