Supported by Grants HL-106286 and HL-13629 from the National Heart, Lung, and Blood Institute.
Transfusion-related acute lung injury–associated HNA-3a antibodies recognize complex determinants on choline transporter-like protein 2
Article first published online: 21 MAY 2014
© 2014 AABB
Volume 54, Issue 12, pages 3208–3215, December 2014
How to Cite
Bougie, D. W., Peterson, J. A., Kanack, A. J., Curtis, B. R. and Aster, R. H. (2014), Transfusion-related acute lung injury–associated HNA-3a antibodies recognize complex determinants on choline transporter-like protein 2. Transfusion, 54: 3208–3215. doi: 10.1111/trf.12717
- Issue published online: 11 DEC 2014
- Article first published online: 21 MAY 2014
- Manuscript Accepted: 6 APR 2014
- Manuscript Revised: 13 MAR 2014
- Manuscript Received: 6 JAN 2014
- National Heart, Lung, and Blood Institute. Grant Numbers: HL-106286, HL-13629
HNA-3a–specific antibodies can cause severe, sometimes fatal, transfusion-related acute lung injury when present in transfused blood. The HNA3-a/b antigens are determined by an R154Q polymorphism in the first of five extracellular (EC) loops of the 10-membrane-spanning choline transporter-like protein 2 (CTL2) expressed on neutrophils, lymphocytes, and other tissues. Approximately 50% of HNA-3a antibodies (Type 1) can be detected using CTL2 Loop 1 peptides containing R154; the remaining 50% (Type 2) fail to recognize this target. Understanding the basis for this difference could guide efforts to develop practical assays to screen blood donors for HNA-3 antibodies.
Study Design and Methods
Reactions of HNA-3a antibodies against recombinant versions of human, mouse, and human/mouse (chimeric) CTL2 were characterized using flow cytometry and various solid-phase assays.
The findings show that, for binding to CTL2, Type 2 HNA-3a antibodies require nonpolymorphic amino acid residues in the third, and possibly the second, EC loops of CTL2 to be in a configuration comparable to that found naturally in the cell membrane. In contrast, Type 1 antibodies require only peptides from the first EC loop that contain R154 for recognition.
Although Type 1 HNA-3a antibodies can readily be detected in solid-phase assays that use a CTL2 peptide containing R154 as a target, development of a practical test to screen blood donors for Type 2 antibodies will pose a serious technical challenge because of the complex nature of the epitope(s) recognized by this antibody subgroup.