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

Authors :
Fageräng, Beatrice
Cyranka, Leon
Schjalm, Camilla
McAdam, Karin Ekholt
Larsen, Carina Sandem
Heinzelbecker, Julia
Gedde-Dahl, Tobias
Würzner, Reinhard
Espevik, Terje
Tjønnfjord, Geir Erland
Garred, Peter
Barratt-Due, Andreas
Tvedt, Tor Henrik Anderson
Mollnes, Tom Eirik
Source :
Frontiers in Immunology; 2024, p1-13, 13p
Publication Year :
2024

Abstract

Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with immune complications and endothelial dysfunction due to intricate donorrecipient 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-1b, 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16643224
Database :
Complementary Index
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
178112090
Full Text :
https://doi.org/10.3389/fimmu.2024.1422370