Editors' ChoiceMicrobiology

Saving Lives by Screening Out

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Science Translational Medicine  06 Jan 2010:
Vol. 2, Issue 13, pp. 13ec3
DOI: 10.1126/scitranslmed.3000770

One of the major causes of mortality after blood transfusions is lung injury, which occurs shortly after the transfusion of blood products that contain unsuspected leukocyte-specific alloantibodies. These alloantibodies, directed against the human neutrophil alloantigen-3a (HNA-3a), occur in individuals lacking the antigen on their own blood cells, a situation that commonly arises during pregnancies in which the mother is exposed to the blood of a fetus who has inherited the antigen from the father. To develop high-throughput assays to screen out blood donors that carry HNA-3a–specific antibodies and prevent transfusion-related lung injury, Greinacher and colleagues have identified the protein constituting the HNA-3a antigen.

To do so, they first purified the protein antigen from granulocytes obtained from HNA-3a–positive and –negative blood donors by means of immunoprecipitation and analyzed the precipitates in tandem by means of liquid chromatography–mass spectrometry (LC-MS). Ten peptides were found in HNA-3a–positive granulocytes through this method, and all of them pointed to the choline transporter–like protein-2 (SLC44A2) as the HNA-3a antigen protein. Single-nucleotide polymorphism (SNP) examination of 54 individuals with the HNA-3a phenotype revealed an association between SNP rs2288904 and the HNA-3a antigen, in which adenine or guanine at nucleotide position 461 determined whether glutamine or arginine, respectively, would be encoded. Individuals homozygous for the SLC344A2 *461G variant encoded the HNA-3a phenotype. In a larger population study of 3700 European individuals, 63.1% were homozygous for 461G, 32.1% were heterozygous for 461G, and 4.8% were homozygous for 461A, which on the basis of these allelic frequencies demonstrates that over 95% of the population are at risk for developing transfusion-related lung injury if transfused with blood containing antibodies to HNA-3a.

The authors showed that HNA-3a–specific antibodies can bind to the region of choline transporter protein that harbors the critical amino acid residues and can cause granulocyte aggregation and activation. These results set the stage for large-scale preventive screening tests of blood donors for alloantibodies reactive to HNA-3a in order to prevent the deleterious consequences associated with transfusion of HNA-3a–positive blood.

A. Greinacher et al., Characterization of human neutrophil alloantigen-3a. Nat. Med. 27 December 2009 (10.1038/nm.2070). [Abstract]

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