Background Antibody-mediated transfusion-related acute lung injury (TRALI) is an important cause of transfusion-associated morbidity and death. Preventive strategies are currently a matter of debate.Methods Specificities of leucocyte antibodies implicated in previous severe TRALI reactions were determined using standard techniques. Based on these results, a leucocyte antibody screening strategy for the testing of parous female donors was introduced. ResultsOf 36 TRALI cases, 17, 12, four and three were due to human leucocyte antigen (HLA) class II, human neutrophil alloantigen (HNA), HLA class I, and mixtures of HLA class I and II antibodies, respectively. HNA-3a antibodies accounted for 10 of 12 HNA antibody-mediated reactions and 6 of 10 fatalities including one after transfusion of red blood cells. Investigation 5332 parous female donors showed leucocyte antibodies in 473 samples, resulting in an alloimmunization rate of 8·9%. Sixty-one per cent of these donors presented HLA class I, 19% class II, 12% HLA class I and II antibodies and 5% HNA antibodies. Additional HLA class I antibodies were found in 39% of HLA class II and in 17% of HNA antibodies containing sera. Our restrictive plasma strategy did not result in a shortage of plasma or platelets. No antibodymediated TRALI case was observed since introduction of the policy of plasma from male, nulliparous or tested multiparous donors. ConclusionCompared to HLA class I antibodies, those directed against HLA class II and HNA-3a were of greater clinical relevance. Isolated HLA class I antibody screening was found to be insufficient for leucocyte antibody screening.

Transfusion-related acute lung injury (TRALI) is a frequent cause of transfusion-associated morbidity and mortality. Severe TRALI is often due to antibodies in blood components directed against the human neutrophil alloantigen-3a (HNA-3a). We show here that the HNA-3a antigen arises from a nucleotide polymorphism in the choline transporter-like protein-2 gene (SLC44A2), with the resulting variation at amino acid position 154 determining the reactivity of the protein with HNA-3a-specific antibodies; the variant with an arginine at this position, rather than a glutamine, constitutes the HNA-3a antigen. The molecular identification of this antigen should facilitate the development of assays for blood donor screening to lower the risk of TRALI.

The PCR-SSP method allows reliable determination of the HNA-3a and -3b genotypes; approximately 7% of HNA-3b homozygous women develop antibodies when exposed to the HNA-3a antigen during pregnancy.