Inhibition of terminal complement complex formation alleviates murine antibody-mediated TRALI

Chen, Dawei, Liang, Huaqin, Xu, Xiuzhang, Xia, Wenjie, Ye, Xin, Luo, Yalin, He, Jiansen, Xu, Yaori, Liu, Jing, Ren, Hui, Luo, Shengxue, Woodruff, Trent M., Zelek, Wioleta M., Morgan, B. Paul ORCID: https://orcid.org/0000-0003-4075-7676, Kapur, Rick, Santoso, Sentot and Fu, Yongshui 2025. Inhibition of terminal complement complex formation alleviates murine antibody-mediated TRALI. Blood 10.1182/blood.2024028012

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Abstract

Transfusion-related acute lung injury (TRALI) is a leading cause of blood transfusion triggered mortality. Recently, we demonstrated the critical role of Fc-dependent complement activation in anti-CD36–mediated murine TRALI. In this study, we found that C5 −/− mice were protected and administration of anti-C5 rescued wild-type mice from anti-CD36–mediated TRALI. However, C5aR1 −/− mice were not protected against anti-CD36–mediated TRALI, implying a possible role of C5b-9 (membrane attack complex [MAC]). Accordingly, elevated levels of MAC were detected in bronchoalveolar lavage fluid and lung tissue of mice with anti-CD36 induced TRALI. Inhibition of MAC formation by administration of anti-C7 blocking monoclonal antibody (mAb) alleviated TRALI in mice, suggesting the critical role of the MAC in the pathology of anti-CD36–mediated TRALI. Furthermore, anti-C7 treatment also led to favorable outcome in anti-MHC I-induced murine TRALI, indicating the potential broader applicability of MAC inhibitors in the treatment of antibody–mediated TRALI. Therefore, this approach may be promising to further explore for the treatment of TRALI patients.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Additional Information:	License information from Publisher: LICENSE 1: Title: This article is under embargo with an end date yet to be finalised.
Publisher:	American Society of Hematology (ASH Publications)
ISSN:	0006-4971
Date of First Compliant Deposit:	9 June 2025
Date of Acceptance:	29 April 2025
Last Modified:	09 Jun 2025 11:15
URI:	https://orca.cardiff.ac.uk/id/eprint/178904

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