Reconstitution of norovirus-specific T cell responses following hematopoietic stem cell transplantation in patients with inborn errors of immunity and chronic norovirus infection.

Autor:	Durkee-Shock J; Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Cohen A; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA., Maghzian N; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA., Pezzella G; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA., Jensen-Wachspress M; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA., Hostal A; Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Barton K; Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Gangler K; Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Dávila Saldaña BJ; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.; Division of Blood and Marrow Transplantation, Children's National Hospital, Washington, DC, USA., Chaimongkol N; Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Bollard CM; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.; Division of Blood and Marrow Transplantation, Children's National Hospital, Washington, DC, USA., Sosnovtsev SV; Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Cohen J; Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Nagata BM; Infectious Disease Pathogenesis Section, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Rockville, MD, USA., Alves DA; Infectious Disease Pathogenesis Section, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Rockville, MD, USA., Ghosh R; NIAID Centralized Sequencing Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Seifert BA; NIAID Centralized Sequencing Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Freeman A; Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Gonzalez C; Immune Deficiency Cellular Therapy Program, National Cancer Institute, Bethesda, MD, USA., Notarangelo LD; Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Green KY; Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Keller MD; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.; Division of Allergy and Immunology, Children's National Hospital, Washington DC, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2024 Aug 14. Date of Electronic Publication: 2024 Aug 14.
DOI:	10.1093/infdis/jiae398
Abstrakt:	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. (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)
Databáze:	MEDLINE
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