Blood transfusion products contain mitochondrial DNA damage-associated molecular patterns: a potential effector of transfusion-related acute lung injury

Abstract

Background: Transfusion-related acute lung injury (TRALI) is the most frequent and severe complication in patients receiving multiple blood transfusions. Current pathogenic concepts hold that proinflammatory mediators present in transfused blood products are responsible for the initiation of TRALI, but the identity of the critical effector molecules is yet to be determined. We hypothesize that mtDNA damage-associated molecular patterns (DAMPs) are present in blood transfusion products, which may be important in the initiation of TRALI.

Methods: DNA was extracted from consecutive samples of packed red blood cells, fresh frozen plasma (FFP), and platelets procured from the local blood bank. Quantitative real-time polymerase chain reaction was used to quantify ≈200 bp sequences from the COX1, ND1, ND6, and D-loop regions of the mitochondrial genome.

Results: A range of mtDNA DAMPs were detected in all blood components measured, with FFP displaying the largest variation.

Conclusions: We conclude that mtDNA DAMPs are present in packed red blood cells, FFP, and platelets. These observations provide proof of the concept that mtDNA DAMPs may be mediators of TRALI. Further studies are needed to test this hypothesis and to determine the origin of mtDNA DAMPs in transfused blood.

Keywords: ARDS; DAMP; Damage-associated molecular patterns; Mitochondria; TRALI; Transfusion; Transfusion-related acute lung injury.

Fig. 1

Consecutive samples from leukocyte-reduced PRBCs reveal varying amounts of mtDNA fragments. Each sample is depicted as a single point and expressed as the fold increase from the negative control.

Fig. 2

Consecutive samples from non–leukocyte-reduced FFP reveal varying amounts of mtDNA fragments. Each sample is depicted as a single point and expressed as the fold increase from the negative control.

Fig. 3

Consecutive samples from non–leukocyte-reduced platelets reveal varying amounts of mtDNA fragments. Each sample is depicted as a single point and expressed as the fold increase from the negative control.