Pathogenesis Of Transfusion-related Acute Lung Injury Research Articles

Transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is an uncommon complication of allogeneic blood transfusion manifested typically by shortness of breath, fever, and hypotension. It has been estimated to occur in 0.04% to 0.16% per patient transfused. TRALI has been identified as an important cause of transfusion-related morbidity and mortality. Despite the increasing recognition that TRALI represents an important clinical syndrome, much about the pathogenesis, treatment, and prevention of TRALI is poorly understood or is controversial. In this report, what is known about TRALI is summarized and some of the areas in which knowledge and/or consensus are currently lacking are identified.

Possible mechanisms underlying development of transfusion‐related acute lung injury: roles of anti‐major histocompatibility complex class II DR antibody

Anti-major histocompatibility complex (anti-MHC) antibodies (Abs) and antipolymorphonuclear neutrophil (anti-PMN) Abs are generally considered as the main causes of the development of transfusion-related acute lung injury (TRALI), which is one of the most severe and sometimes lethal side effects of transfusion. These Abs are postulated to activate recipient's leucocytes, resulting in the release of soluble factors such as reactive oxygen species and detrimental cytokines and chemokines. The harmful effects on the lung tissues and resident leucocytes of these malignant factors are suspected to be profoundly involved in TRALI reactions. Several reports have indicated the principle effect of biologically active lipids on the pathogenesis of TRALI. However, the precise mechanisms of TRALI development remain unclear. To resolve this issue, we have been investigating cytokines that induce continuous inflammation of the lungs, specifically focusing on the cytokines derived from activated PMNs. We observed that the granulocyte-macrophage colony-stimulating factor (GM-CSF) markedly enhances the expression of MHC class II DR in PMNs. Moreover, MHC class II DR-expressing PMNs were also proved to express a high-affinity receptor for immunoglobulin E (IgE) (FcepsilonRI) and to produce tumour necrosis factor-alpha, interferon-gamma and interleukin-18 following a challenge with an anti-MHC class II DR monoclonal Ab (MoAb) or anti-DR antiserum. It is strongly suggested that amongst various inflammatory mediators, at least these three cytokines may contribute to the duration of inflammatory reactions in the lungs. Furthermore, FcepsilonRI expression, in GM-CSF-treated PMNs, suggests the involvement of PMNs in IgE-mediated immune reactions.

Prevalence of HLA sensitization in female apheresis donors.

Transfusion-related acute lung injury (TRALI) is a serious complication of plasma-containing blood components. Studies have implicated HLA antibodies along with biologically active lipids in stored blood in the pathogenesis of TRALI. It has been proposed that the exclusion of HLA-untested, multiparous donors of plasma-rich components, including plasma and single-donor apheresis platelets, would substantially reduce the risk of TRALI. To investigate the feasibility of such an exclusion, 332 female plateletpheresis donors with a record of over 9000 donations, none of which were associated with TRALI, were studied. Seventeen percent of female donors demonstrated HLA sensitization. Parity and HLA sensitization were significantly correlated (p<0.0001), with sensitized donors having an average of 2.9 (+/- 0.6 95% CI) prior pregnancies and unsensitized donors having an average of 1.8 (+/- 0.2 95% CI) prior pregnancies. The percentage of HLA-sensitized women with 0, 1 to 2, and > or = 3 pregnancies was 7.8, 14.6, and 26.3, respectively. These findings confirm the hypothesis that multiparous women (> or = 3 pregnancies) represent an increased potential risk for TRALI. However, the exclusion of multiparous plateletpheresis donors would eliminate one-third of our female donor pool. Screening such donors for HLA sensitization may represent the optimal approach for identifying donors at risk for causing TRALI, but this still would result in the deferral of 8 percent of female plateletpheresis donors. At present, prospective screening to identify donors at risk for causing TRALI is not justified.

Transfusion‐related acute lung injury due to HLA‐A2‐specific antibodies in recipient and NB1‐specific antibodies in donor blood

Transfusion-related acute lung injury (TRALI) is a hazardous but little-known complication of blood transfusion, characterized by non-cardiogenic lung oedema after blood transfusion. Leucoagglutinating antibodies in the donor plasma are considered to play a central role in the pathogenesis of TRALI but no recommended procedure currently exists for their detection, and most of them have not yet been well characterized. Serum samples of two patients who have developed TRALI within 30 min of blood transfusion and the sera of the involved blood donors were investigated for leucocyte antibodies by granulocyte immunofluorescence, granulocyte agglutination and lymphocytotoxicity assays using typed test cells. Suspected specificities of the detected antibodies were confirmed by a luminoimmunoblot assay and the antigen capture assay MAIGA. One case was associated with granulocyte agglutinating anti-HLA-A2 antibodies in the recipient's (i.e. patient's) own blood and the other with donor-related non-agglutinating antibodies directed against the granulocyte-specific antigen NB1. Leucocyte incompatibility between donor and recipient was shown in both cases by crossmatching and typing of the incompatible cells for the appropriate antigen. The results show that TRALI is associated not only with donor- but also with recipient-related leucocyte antibodies. In addition to leucoagglutinating antibodies, non-agglutinating granulocyte-specific antibodies can be also involved. For immunodiagnosis, sera from both must be investigated by a combination of granulocyte and lymphocyte (HLA) antibody screening tests and leucocyte incompatibility verified by crossmatching.