Medical College of Wisconsin
CTSIResearch InformaticsREDCap

The neutrophil alloantigen HNA-3a (5b) is located on choline transporter-like protein 2 and appears to be encoded by an R>Q154 amino acid substitution. Blood 2010 Mar 11;115(10):2073-6

Date

12/31/2009

Pubmed ID

20040764

Pubmed Central ID

PMC2837332

DOI

10.1182/blood-2009-11-248336

Scopus ID

2-s2.0-77950438788 (requires institutional sign-in at Scopus site)   88 Citations

Abstract

The molecular basis of the HNA-3a/b (5b/a) leukocyte antigen system has not yet been defined despite evidence that HNA-3a-specific antibodies are particularly prone to cause severe, often fatal, transfusion-related lung injury. We used genome-wide single nucleotide polymorphism scanning and sequencing of DNA from persons of different HNA-3a/b phenotypes to identify a single single nucleotide polymorphism in exon 7 of the CLT2 gene (SLC44A2) that predicts an amino acid substitution in the first extracellular loop of choline transporter-like protein 2, a member of the choline transporter-like protein family of membrane glycoproteins, and correlates perfectly with HNA-3a/b phenotypes (R154 encodes HNA-3a; Q154 encodes HNA-3b). Mass spectrometric analysis of proteins immunoprecipitated from leukocytes by anti-HNA-3a provided direct evidence that anti-HNA-3a recognizes choline transporter-like protein 2. These findings will enable large-scale genotyping for HNA-3a/b to identify blood donors at risk to have HNA-3a-specific antibodies and should facilitate development of practical methods to detect such antibodies and prevent transfusion-related lung injury.

Author List

Curtis BR, Cox NJ, Sullivan MJ, Konkashbaev A, Bowens K, Hansen K, Aster RH

Authors

Richard H. Aster MD Professor in the Medicine department at Medical College of Wisconsin
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

Amino Acid Sequence
Amino Acid Substitution
Arginine
Base Sequence
DNA Mutational Analysis
Genome-Wide Association Study
Glutamic Acid
Humans
Isoantigens
Mass Spectrometry
Membrane Glycoproteins
Membrane Transport Proteins
Molecular Sequence Data
Mutant Proteins
Neutrophils
Polymorphism, Single Nucleotide