J Infect Dis. 2024 Aug 14. pii: jiae398. [Epub ahead of print]
Jessica Durkee-Shock,
Ariella Cohen,
Naseem Maghzian,
Gloria Pezzella,
Mariah Jensen-Wachspress,
Anna Hostal,
Karenna Barton,
Krista Gangler,
Blachy J Dávila Saldaña,
Natthawan Chaimongkol,
Catherine M Bollard,
Stanislav V Sosnovtsev,
Jeffrey Cohen,
Bianca M Nagata,
Derron A Alves,
Rajarshi Ghosh,
Bryce A Seifert,
Alexandra Freeman,
Corina Gonzalez,
Luigi D Notarangelo,
Kim Y Green,
Michael D Keller.
BACKGROUND: Chronic norovirus infection (CNI) causes significant morbidity in immunocompromised patients. No effective prevention or treatment currently exists.METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
Keywords: Chronic Norovirus; DOCK8 deficiency; Hematopoietic stem cell transplantation; Severe Combined Immunodeficiency; T cell immunity