The neutrophil antigen 3a/b polymorphism in <i>SLC44A2</i> unexpectedly encodes the Csa/Csb red cell antigens
Abstract
Abstract The Csa blood group antigen was identified &gt;50 years ago, but its genetic basis has yet to be elucidated. All our recent genomic investigation has failed to resolve the genetic basis of this enigmatic antigen. By investigating the association of the human neutrophil antigen (HNA)-3a/b polymorphism (rs2288904-G/A) in SLC44A2 with clinical features of sickle cell disease, we incidentally discovered that rare subjects with the homozygous HNA-3b/b genotype also carry the uncommon Cs(a–) phenotype. We genotyped this single-nucleotide polymorphism in a cohort of 25 Cs(a–) subjects and found that all of them showed an HNA-3b/b genotype. This result suggests that the high-prevalence allele with rs2288904 (HNA-3a; 455G) encoding Arg152 encodes the high-prevalence Csa. Accordingly, anti-Csa does not react with solute carrier (SLC)44A2null red blood cells (RBCs), SLC44A2 knockout K562 cells, and K562 cells expressing HNA-3b, confirming that the Csa and Csb antigens are carried on this protein. Furthermore, mass spectrometry analysis of SLC44A2 from neutrophils and RBCs, along with serological investigation, showed that, despite HNA-3a and Csa having the same genetic basis, anti–HNA-3a and anti-Csa recognize different epitopes on the SLC44A2 protein. Overall, our data resolve the genetic bases of the Cs(a–) and Cs(b–) blood phenotypes, with new insights on the anti–HNA-3a specificity.
Article Details
Authors (21)
Romain Duval
1Université Paris Cité and Université des Antilles, INSERM, Unité Mixte de Recherche (UMR)-S1134, Laboratory of Blood Group Antigens, Hematopoiesis and Sickle Cell Disease, Paris, France
Alissa Soudry
1Université Paris Cité and Université des Antilles, INSERM, Unité Mixte de Recherche (UMR)-S1134, Laboratory of Blood Group Antigens, Hematopoiesis and Sickle Cell Disease, Paris, France
Jonathan De Oliveira Rios
1Université Paris Cité and Université des Antilles, INSERM, Unité Mixte de Recherche (UMR)-S1134, Laboratory of Blood Group Antigens, Hematopoiesis and Sickle Cell Disease, Paris, France
Sarah Liane Linguet
1Université Paris Cité and Université des Antilles, INSERM, Unité Mixte de Recherche (UMR)-S1134, Laboratory of Blood Group Antigens, Hematopoiesis and Sickle Cell Disease, Paris, France
Miguel Taillepierre
1Université Paris Cité and Université des Antilles, INSERM, Unité Mixte de Recherche (UMR)-S1134, Laboratory of Blood Group Antigens, Hematopoiesis and Sickle Cell Disease, Paris, France
Graziella Matesic
1Université Paris Cité and Université des Antilles, INSERM, Unité Mixte de Recherche (UMR)-S1134, Laboratory of Blood Group Antigens, Hematopoiesis and Sickle Cell Disease, Paris, France
Alexandre Raneri
2Centre National de Référence pour les Groupes Sanguins, Établissement Français du Sang Ile-de-France, Paris, France
Guy Laiguillon
2Centre National de Référence pour les Groupes Sanguins, Établissement Français du Sang Ile-de-France, Paris, France
Emilie Le Toriellec
5Laboratoire Human Leukocyte Antigen, Département d'Immunologie Leucoplaquettaire, Établissement Français du Sang Ile-de-France, Créteil, France
Emilie-Fleur Gautier
5Laboratory of Excellence Globule Rouge d’Excellence, Proteom’IC Facility, Université Paris Cité, Centre National de la Recherche Scientifique, INSERM, Institut Cochin, Paris, France
Damien Vainqueur
1Université Paris Cité and Université des Antilles, INSERM, Unité Mixte de Recherche (UMR)-S1134, Laboratory of Blood Group Antigens, Hematopoiesis and Sickle Cell Disease, Paris, France
Jérôme Babinet
2Centre National de Référence pour les Groupes Sanguins, Établissement Français du Sang Ile-de-France, Paris, France
Cécile Masson
7Bioinformatics Core Facility, Institut Imagine-Structure Fédérative de Recherche Necker, INSERM U1163 and INSERM US24/CNRS UAR3633, Université Paris Cité, Paris, France
Jean Christophe Gelly
1Université Paris Cité and Université des Antilles, INSERM, Unité Mixte de Recherche (UMR)-S1134, Laboratory of Blood Group Antigens, Hematopoiesis and Sickle Cell Disease, Paris, France
Caroline Le Van Kim
Marc Romana
1Université Paris Cité and Université des Antilles, INSERM, Unité Mixte de Recherche (UMR)-S1134, Laboratory of Blood Group Antigens, Hematopoiesis and Sickle Cell Disease, Paris, France
Dawei Chen
State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Advanced Catalytic Engineering Research Center of the Ministry of Education
Sentot Santoso
1Institute of Blood Transfusion, Guangzhou Blood Centre, Guangzhou, China
Berengere Koehl
1Université Paris Cité and Université des Antilles, INSERM, Unité Mixte de Recherche (UMR)-S1134, Laboratory of Blood Group Antigens, Hematopoiesis and Sickle Cell Disease, Paris, France
Thierry Peyrard
Etablissement Français du Sang
Slim Azouzi
1Université Paris Cité and Université des Antilles, INSERM, Unité Mixte de Recherche (UMR)-S1134, Laboratory of Blood Group Antigens, Hematopoiesis and Sickle Cell Disease, Paris, France