High‐throughput Kell, Kidd, and Duffy matrix‐assisted laser desorption/ionization, time‐of‐flight mass spectrometry–based blood group genotyping of 4000 donors shows close to full concordance with serotyping and detects new alleles. Issue 12 (21st May 2014)

• Record Type: Journal Article
• Authors: Meyer, Stefan; Vollmert, Caren; Trost, Nadine; Brönnimann, Chantal; Gottschalk, Jochen; Buser, Andreas; Frey, Beat M.; Gassner, Christoph
• Is Part Of: Transfusion. Volume 54:Issue 12(2014)
• Page Start: 3198
• Page End: 3207
• Publication Date: 2014-05-21
• Subjects: Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; Blood Group Antigens -- Periodicals; Blood Preservation -- Periodicals; Blood Transfusion -- Periodicals; 615
• DOI: 10.1111/trf.12715
• Languages: English
• ISSNs: 0041-1132

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="trf12715-sec-0001" sec-type="section"> <title>Background</title> <p>After the ABO (<italic>ABO</italic>) and Rh (<italic>RHD</italic> and <italic>RHCE</italic>) blood group systems, Kell (<italic>KEL</italic>), Kidd (<italic>SLC14A1</italic>), and Duffy (<italic>DARC</italic>) represent the second most important clinically relevant antigens.</p> </sec> <sec id="trf12715-sec-0002" sec-type="section"> <title>Study Design and Methods</title> <p>Samples from 4000 Swiss blood donors, with serologic prevalues for K/k, Kp<sup>a/b</sup>, Jk<sup>a/b</sup>, and Fy<sup>a/b</sup>, and 48 additional samples of presumptive black African origin were genotyped using high‐throughput matrix‐assisted laser desorption/ionization, time‐of‐flight mass spectrometry, applying one single‐multiplex polymerase chain reaction/primer‐extension reaction simultaneously detecting 15 single‐nucleotide polymorphisms.</p> </sec> <sec id="trf12715-sec-0003" sec-type="section"> <title>Results</title> <p>Genotype/phenotype concordance for K/k, Kp<sup>a/b</sup>, Jk<sup>a/b</sup>, and all Fy<sup>a/b</sup> specificities were 100, 99.98, 99.93, and 99.20%, respectively. Discrepancies were caused by erroneous serologic profiles (n = 33), mainly attributed to weakly expressed Fy<sup>x</sup> (n = 28). Only three discrepancies had a genetic basis. They could all be explained by newly observed silenced alleles: one <italic>KEL</italic>*<italic>02N.34</italic> and one <italic>FY</italic>*<italic>02N.03</italic> with predicted R700Q and G261R amino acid exchanges, respectively, and one <italic>JK</italic>*<italic>B</italic>, with an as‐yet‐unidentified silencing cause. According to NCBI SNP database entry for rs8176034, another new allele, <italic>KEL</italic>*<italic>02.38</italic>, had been expected, and we formally demonstrated its presence. We furthermore identified individuals with rare phenotypes, such as Js<sup>a/b</sup> heterozygotes among Caucasians, rare alleles, the "Swiss" <italic>JK</italic>*<italic>01N.03</italic>, and rare genotypes, such as one Fy<sup>x</sup> homozygote.</p> </sec> <sec id="trf12715-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Genotyping proved its practicability in the daily routine setting and qualitatively outperformed serology. Technology is ideal for time‐insensitive donor genotyping and allows for a broad range of throughput needs. Consequently, from a technologic point of view, serotyping should be replaced by genotyping for donors' blood groups encoded by <italic>KEL</italic>, <italic>SLC14A1</italic>, and <italic>DARC</italic>.</p> </sec> </abstract>