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© Research
Publication : The Journal of allergy and clinical immunology

Late-onset enteric virus infection associated with hepatitis (EVAH) in transplanted SCID patients.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of allergy and clinical immunology - 10 Jan 2023

Riller Q, Fourgeaud J, Bruneau J, De Ravin SS, Smith G, Fusaro M, Meriem S, Magerus A, Luka M, Abdessalem G, Lhermitte L, Jamet A, Six E, Magnani A, Castelle M, Lévy R, Lecuit MM, Fournier B, Winter S, Semeraro M, Pinto G, Abid H, Mahlaoui N, Cheikh N, Florkin B, Frange P, Jeziorski E, Suarez F, Sarrot-Reynauld F, Nouar D, Debray D, Lacaille F, Picard C, Pérot P, Regnault B, Da Rocha N, de Cevins C, Delage L, Pérot BP, Vinit A, Carbone F, Brunaud C, Marchais M, Stolzenberg MC, Asnafi V, Molina T, Rieux-Laucat F, Notarangelo LD, Pittaluga S, Jais JP, Moshous D, Blanche S, Malech H, Eloit M, Cavazzana M, Fischer A, Ménager MM, Neven B,

Link to Pubmed [PMID] – 36638922

Link to 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