Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Characterization of the human neutrophil alloantigen-3a


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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Reactivity of antibodies specific for HNA-3a.


  1. Holness, L., Knippen, M.A., Simmons, L. & Lachenbruch, P.A. Transfus. Med. Rev. 18, 184–188 (2004).

    Article  Google Scholar 

  2. Vamvakas, E.C. & Blajchman, M.A. Blood 113, 3406–3417 (2009).

    Article  CAS  Google Scholar 

  3. Kleinman, S. et al. Transfusion 44, 1774–1789 (2004).

    Article  Google Scholar 

  4. Chapman, C.E. et al. Transfusion 49, 440–452 (2009).

    Article  Google Scholar 

  5. Middelburg, R.A., van Stein, D., Briet, E. & van der Bom, J.G. Transfusion 48, 2167–2176 (2008).

    Article  Google Scholar 

  6. Bux, J. & Sachs, U.J.H. Br. J. Haematol. 136, 788–799 (2007).

    Article  CAS  Google Scholar 

  7. Strong, D.M. & Shoos Lipton, K. 〈〉 (2006).

  8. Silliman, C.C. et al. Blood 101, 454–462 (2003).

    Article  CAS  Google Scholar 

  9. Khan, S.Y. et al. Blood 108, 2455–2462 (2006).

    Article  CAS  Google Scholar 

  10. Popovsky, M.A. & Moore, S.B. Transfusion 25, 573–577 (1985).

    Article  CAS  Google Scholar 

  11. Reil, A., Keller-Stanislawski, B., Guenay, S. & Bux, J. Vox Sang. 95, 313–317 (2008).

    Article  CAS  Google Scholar 

  12. van Leeuwen, A., Eernise, J.G. & van Rood, J.J. Vox Sang. 9, 431–446 (1964).

    Article  CAS  Google Scholar 

  13. Davoren, A. et al. Transfusion 43, 641–645 (2003).

    Article  CAS  Google Scholar 

  14. Seeger, W. et al. Blood 76, 1438–1444 (1990).

    CAS  PubMed  Google Scholar 

  15. Kopko, P.M. et al. J. Am. Med. Assoc. 287, 1968–1971 (2002).

    Article  Google Scholar 

  16. ISBT Working Party on Granulocyte Immunobiology. et al. Vox Sang. 96, 266–269 (2009).

  17. de Haas, M. et al. Transfusion 40, 222–227 (2000).

    Article  CAS  Google Scholar 

  18. Nair, T.S. et al. J. Neurosci. 24, 1772–1779 (2004).

    Article  CAS  Google Scholar 

  19. Keller-Stanislawski, B., Reil, A., Günay, S. & Funk, M.B. Vox Sang. 98, 70–77 (2009).

    Article  Google Scholar 

  20. Soehnlein, O. & Lindbom, L. J. Leukoc. Biol. 85, 344–351 (2009).

    Article  CAS  Google Scholar 

  21. Yasui, K. et al. Transfusion 48, 978–987 (2008).

    CAS  PubMed  Google Scholar 

Download references


We thank A. Teumer for running the data analysis of the Study on Health in Pomerania for population-wide gene frequency analysis of the HNA-3a–encoding polymorphism. We highly appreciate the expertise and support of J. Hoppen and H. Hippe (Chromatec) for expression of recombinant protein fragments. We thank T.E. Warkentin for valuable discussion and suggestions. This work was supported by an unrestricted grant of the Deutsche Rote Kreuz-Blutspendedienst West, Hagen, Germany; by the Land Mecklenburg-Vorpommern, Exzellenzinitiative UG 07-064; by the Bundesministerium für Bildung und Forschung, Zentrum für Innovationskompetenz Humorale Immunreaktionen bei Herz-Kreislauf Erkrankungen (ZIK-HIKE) 03Z2CK1 and 03Z2CI1 and Zentrum für Innovationskompetenz Funktionelle Genomforschung (ZIK FunGene 03ZIK331).

Author information

Authors and Affiliations



A.G. designed the study, supervised the experiments, evaluated the results and wrote the manuscript. J.W. performed the immunoprecipitation studies, evaluated the experiments and wrote the manuscript. E.H. and U.V. performed the mass spectrometry experiments, characterized the protein and wrote the manuscript. B.F. affinity-purified the antibodies and performed the flow cytometry and chemiluminescence experiments. A.R. and J.B. contributed the human antibodies, characterized the granulocytes serologically, developed the sequence-specific PCR method, performed all granulocyte aggregation tests and wrote the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Andreas Greinacher.

Ethics declarations

Competing interests

The Deutsche Rote Kreuz Blutspendedienst West Hagen and the University Greifswald submitted a patent application to the Deutsche Patent und Markenamt to use the HNA-31 epitope for screening of blood donors.

Supplementary information

Supplementary Text and Figures

Supplementary Figure 1, Supplementary Table 1 and Supplementary Methods (PDF 423 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Greinacher, A., Wesche, J., Hammer, E. et al. Characterization of the human neutrophil alloantigen-3a. Nat Med 16, 45–48 (2010).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing