Mechanisms of transfusion-related acute lung injury (TRALI): Anti-leukocyte antibodies

Abstract

There is abundant evidence that leukocyte antibodies in blood donor products are somehow involved in transfusion-related acute lung injury (TRALI). Human leukocyte antigen (HLA) class I, HLA class II, and neutrophil-specific antibodies in the plasma of both blood donors and recipients have been implicated in the pathogenesis of TRALI. The case for a relationship between leukocyte antibodies and TRALI is more compelling if concordance between the antigen specificity of the leukocyte antibodies in the donor plasma and the corresponding antigen on the cells of the affected recipient is demonstrated. Such antibody-antigen concordance can be investigated by typing the recipient for the cognate leukocyte antigens or by cross-matching the donor plasma against the recipient's leukocytes. Two proposed pathophysiologic mechanisms for TRALI have received the most attention: the antibody hypothesis and the two-event hypothesis. The final common pathway in all of the proposed pathogenic mechanisms of TRALI is increased pulmonary capillary permeability, which results in movement of plasma into the alveolar space causing pulmonary edema. A typical TRALI serologic workup consists of tests for HLA class I and II and neutrophil-specific antibodies. The use of flow cytometry and HLA-coated microbeads is recommended for detection of HLA antibodies in plasma of implicated blood donors and a combination of the granulocyte agglutination test and granulocyte immunofluorescence test for detection of neutrophil-specific antibodies. Genotyping for class I and II HLA and for a limited number of neutrophil antigens may also be helpful in establishing antibody-antigen concordance.

The neutrophil alloantigen HNA-3a (5b) is located on choline transporter-like protein 2 and appears to be encoded by an R>Q154 amino acid substitution

“…3,6 Isolation of neutrophils, T and B lymphocytes, and platelets from normal donor blood, detection of antibodies reactive with these cells by flow cytometry and agglutination, and immunoprecipitation of membrane proteins have been described previously. [7][8][9] …”

Massive right-sided colon diverticular bleeding complicated by the transfusion related acute lung injury (TRALI)

“…All sorts of blood products can be causative agents, the most common being platelet concentrates and FFP [3,4,6,9]. There are two leading theories explaining possible pathways [5,7]. According to the first, TRALI is a consequence of host human leukocyte antigens (HLA) or non-HLA and transfused donor antibody reaction on the surface of neutrophilic leukocytes, which leads to their activation, interstitial and alveolar edema, hyaline membrane formation and destruction of normal lung parenchyma [3][4][5][6][7]9].…”

“…There are two leading theories explaining possible pathways [5,7]. According to the first, TRALI is a consequence of host human leukocyte antigens (HLA) or non-HLA and transfused donor antibody reaction on the surface of neutrophilic leukocytes, which leads to their activation, interstitial and alveolar edema, hyaline membrane formation and destruction of normal lung parenchyma [3][4][5][6][7]9]. The econd theory is popularly known as the "two event" model whereby massive transfusion, major surgery, active bacterial or viral infection and cytokine administration or some other stimulus, prime the immune system and are considered to form the "first event" [2-7,9,10].…”

“…TRALI is a transfusion reaction clinically presenting as acute lung injury temporally connected to transfusion [1][2][3][4][5]. TRALI usually appears within 6 hours of transfusion and resolves in 72 to 96 hours with aggressive respiratory support showing mortality rates of about 5 to 10% [1][2][3][4][6][7][8]. Precise incidence of TRALI is unknown, ranging from 1 case in 1323 to 1 case in 5408 transfused units [3,4,6].…”

TRALI : aspects physiopathologiques

“…Ces anticorps semblent fréquents au cours du TRALI [22]. Les anticorps dirigés contre les antigènes spécifiques des polynucléaires HNA-3a ou 5b sont rares mais à l'origine de formes sévères de TRALI [24]. Il est probable qu'en présence de ces anticorps dangereux activant directement les polynucléaires, comme les anti-HNA-3a, l'étape de priming n'est pas indispensable.…”