Mechanism and intervention of murine transfusion-related acute lung injury caused by anti-CD36 antibodies

Abstract

Anti-CD36 antibodies have been suggested to induce transfusion-related acute lung injury (TRALI) upon blood transfusion, particularly in Asian populations. However, little is known about the pathological mechanism of anti-CD36-mediated TRALI, and potential therapies haven't yet been identified. Here, we developed a murine model of anti-CD36-mediated TRALI to address these questions. We found that administration of mouse monoclonal antibody against CD36 (mAb GZ1) or human anti-CD36 IgG, but not GZ1 F(ab')2 fragments, induced severe TRALI in Cd36 +/+ male mice. Pre-depletion of recipient monocytes or complement, but not neutrophils or platelets, prevented the development of murine TRALI. Moreover, plasma C5a levels after TRALI induction by anti-CD36 were increased more than 3-fold, implying a critical role of complement C5 activation in the mechanism of Fc-dependent anti-CD36-mediated TRALI.Administration of GZ1 F(ab')2, antioxidant (NAC) or C5-blocker (mAb BB5.1) before TRALI induction completely protected mice from anti-CD36-mediated TRALI. Although no significant amelioration in TRALI was observed when mice were injected with GZ1 F(ab')2 after TRALI induction, significant improvement was achieved when mice were treated post-induction with NAC or anti-C5. Importantly, anti-C5 treatment completely rescued mice from TRALI, suggesting the potential role of existing anti-C5 drugs in the treatment of patients with TRALI caused by anti-CD36.

The role of CD36 antibodies in haematopoietic stem cell transplantation

“…CD36 antibody has been reported to be involved in the pathophysiology of transfusion‐related acute lung injury (TRALI), a severe complication of blood transfusion. The patho‐mechanism of TRALI caused by CD36 antibodies has been explained by the expression of CD36 on human monocytes as well as on endothelial cells [2]. Once platelets and monocytes are activated by CD36 antibodies, they release inflammatory mediators, which increase alveolar vascular permeability, but these antibodies can also directly damage endothelial cells.…”

The importance of disrupting complement activation in acute lung injury

“…In addition, we believe it would be worthwhile to investigate directly targeting complement activation, a consequence of IgG hexamerization. The critical importance of complement in alloantibody-mediated acute lung injury was highlighted in recent studies, based on anti–major histocompatibility complex I (antibody clone 34-1-2S) ( 2 , 3 ) and anti-CD36 ( 4 ). Furthermore, in a large cohort of 53 patients with TRALI, plasma complement levels were found to be increased ( 3 ).…”