The function of the complement system remains fully intact throughout the course of allogeneic stem cell transplantation.

Autor:	Fageräng B; Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway.; Department of Clinical Immunology, Laboratory of Molecular Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Cyranka L; Department of Clinical Immunology, Laboratory of Molecular Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Schjalm C; Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway., McAdam KE; Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway., Larsen CS; Department of Hematology, Oslo University Hospital, Oslo, Norway., Heinzelbecker J; Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway., Gedde-Dahl T; Department of Hematology, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Würzner R; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria., Espevik T; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway., Tjønnfjord GE; Department of Hematology, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Garred P; Department of Clinical Immunology, Laboratory of Molecular Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Barratt-Due A; Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway., Tvedt THA; Department of Hematology, Oslo University Hospital, Oslo, Norway., Mollnes TE; Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway.; Research Laboratory, Nordland Hospital, Bodø, Norway.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Jun 13; Vol. 15, pp. 1422370. Date of Electronic Publication: 2024 Jun 13 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1422370
Abstrakt:	Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with immune complications and endothelial dysfunction due to intricate donor-recipient interactions, conditioning regimens, and inflammatory responses. Methods: This study investigated the role of the complement system during HSCT and its interaction with the cytokine network. Seventeen acute myeloid leukemia patients undergoing HSCT were monitored, including blood sampling from the start of the conditioning regimen until four weeks post-transplant. Clinical follow-up was 200 days. Results: Total complement functional activity was measured by WIELISA and the degree of complement activation by ELISA measurement of sC5b-9. Cytokine release was measured using a 27-multiplex immuno-assay. At all time-points during HSCT complement functional activity remained comparable to healthy controls. Complement activation was continuously stable except for two patients demonstrating increased activation, consistent with severe endotheliopathy and infections. In vitro experiments with post-HSCT whole blood challenged with Escherichia coli , revealed a hyperinflammatory cytokine response with increased TNF, IL-1β, IL-6 and IL-8 formation. Complement C3 inhibition markedly reduced the cytokine response induced by Staphylococcus aureus , Aspergillus fumigatus , and cholesterol crystals. Discussion: In conclusion, HSCT patients generally retained a fully functional complement system, whereas activation occurred in patients with severe complications. The complement-cytokine interaction indicates the potential for new complement-targeting therapeutic strategies in HSCT. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Fageräng, Cyranka, Schjalm, McAdam, Larsen, Heinzelbecker, Gedde-Dahl, Würzner, Espevik, Tjønnfjord, Garred, Barratt-Due, Tvedt and Mollnes.)
Databáze:	MEDLINE
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