Moderator of 1 Session
Presenter of 2 Presentations
Introduction to Curative Treatments Hemopoietic Stem Cell Transplant
LATE-ONSET ENTERIC VIRUS INFECTION ASSOCIATED WITH HEPATITIS (EVAH) IN TRANSPLANTED SCID PATIENTS
Abstract
Background and Aims
Allogenic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are potentially curative treatments of severe combined immunodeficiency (SCID). Nevertheless, late-onset manifestations are not uncommon including hepatitis.
Methods
SCID patients with late-onset hepatitis post HSCT or GT were investigated using multi-omics, pathology and metagenomics.
Results
Eleven patients developed persistent hepatitis at a median time of 6 years for SCID related to IL2RG (n=10) or DCLRE1C (n=1) deficiency (SCIDH+). Clinical consequences of this condition can be severe, up to death (n=3). It was associated with the detection of enteric viruses (Aichi virus, Norovirus and Sapovirus) in liver and/or stools, which were not found in stools of healthy asymptomatic similarly transplanted patients (n=12, SCIDH-). Mass-cytometry analysis on peripheral blood mononuclear cells of 6 SCIDH+ compared to 7 SCIDH- identified an expansion of CD38high HLA-DRhigh CD127low CD8+ T cells. Type I and II IFN signatures identified by scRNAseq were mostly but not exclusively found in CD8+ T cells. Among a cohort of 114 long-term survivors post HSCT or GT for SCID, hepatitis was strongly associated with absence of myeloablation, split chimerism and defective B cell function.
Conclusions
Overall, this condition characterized by enteric virus infection associated with hepatitis (named EVAH) represents 25% of SCID patients who did not receive myeloablation and were on immunoglobulin replacement. Partially myeloablative re-transplantation or GT could reconstitute T and B cell immunity and lead to remission of hepatitis, concomitantly to viral clearance, as observed in 5 patients. Beyond SCID, a same dysimmune process could occur in inherited or acquired B-cell defects.