Faculty Collaboration Database

Transfusion-related acute lung injury-associated HNA-3a antibodies recognize complex determinants on choline transporter-like protein 2. Transfusion 2014 Dec;54(12):3208-15

Date

05/23/2014

Pubmed ID

24846273

Pubmed Central ID

PMC4240753

DOI

10.1111/trf.12717

Scopus ID

2-s2.0-84916606351 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

BACKGROUND: 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.

RESULTS: 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.

CONCLUSION: 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.

Author List

Bougie DW, Peterson JA, Kanack AJ, Curtis BR, Aster RH

Author

Brian Curtis PhD Director in the Platelet & Neutrophil Immunology Laboratory department at BloodCenter of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Lung Injury
Animals
Autoantibodies
Blood Donors
Blood Transfusion
Disease Models, Animal
Donor Selection
Female
HEK293 Cells
Humans
Isoantigens
Male
Membrane Glycoproteins
Membrane Transport Proteins
Mice
Protein Structure, Secondary
Recombinant Fusion Proteins