{Reference Type}: Journal Article
{Title}: Reconstitution of norovirus-specific T cell responses following hematopoietic stem cell transplantation in patients with inborn errors of immunity and chronic norovirus infection.
{Author}: Durkee-Shock J;Cohen A;Maghzian N;Pezzella G;Jensen-Wachspress M;Hostal A;Barton K;Gangler K;Dávila Saldaña BJ;Chaimongkol N;Bollard CM;Sosnovtsev SV;Cohen J;Nagata BM;Alves DA;Ghosh R;Seifert BA;Freeman A;Gonzalez C;Notarangelo LD;Green KY;Keller MD;
{Journal}: J Infect Dis
{Volume}: 0
{Issue}: 0
{Year}: 2024 Aug 14
{Factor}: 7.759
{DOI}: 10.1093/infdis/jiae398
{Abstract}: <B>BACKGROUND: </B>Chronic norovirus infection (CNI) causes significant morbidity in immunocompromised patients. No effective prevention or treatment currently exists.<BR><B>METHODS: </B>Two patients with inborn errors of immunity, X- linked severe combined immunodeficiency (X-SCID) and DOCK8 deficiency, were followed longitudinally for clinical course, immune reconstitution, norovirus-specific T cell (NST) response, B cell reconstitution, and norovirus-specific antibody production. Samples were obtained in the peri-hematopoietic stem cell transplant setting (HSCT) before and after CNI clearance. The norovirus strain causing CNI was followed longitudinally for norovirus stool viral loads and sequencing.<BR><B>RESULTS: </B>The noroviruses were identified as GII.4 Sydney[P4 New Orleans] in one patient and GII.17[P17] in the other. An exacerbation of diarrhea post-HSCT in the patient with X-SCID was consistent with norovirus infection but not with graft-vs-host-disease on pathologic samples. Both patients recovered polyfunctional NSTs in the CD4 and CD8 T cell compartments which recognized multiple norovirus structural and non-structural viral antigens. T cell responses were minimal during active CNI but detectable after resolution. Mapping of norovirus-specific T cell responses between the patient with DOCK8 and his matched sibling donor were nearly identical. B cell reconstitution or new endogenous antibody production for IgA or IgG were not observed.<BR><B>CONCLUSIONS: </B>This report is the first to demonstrate reconstitution of norovirus-specific T cell immunity after HSCT closely temporally aligned with clearance of CNI suggesting that cellular immunity is sufficient for norovirus clearance.