The neutrophil antigen 3a/b polymorphism in <i>SLC44A2</i> unexpectedly encodes the Csa/Csb red cell antigens
The Csa blood group antigen was identified >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.
Authors
- Emilie‐Fleur Gautier (ORCID: https://orcid.org/0000-0002-0394-6606)
- Bérengère Koehl (ORCID: https://orcid.org/0000-0001-7087-7199)
- Alexandre Raneri
- Sentot Santoso (ORCID: https://orcid.org/0000-0001-6943-3945)
- Sarah Liane Linguet (ORCID: https://orcid.org/0000-0002-2547-3723)
- Jérôme Babinet
- Jonathan De Oliveira Rios (ORCID: https://orcid.org/0000-0002-1679-7478)
- Damien Vainqueur
- Slim Azouzi (ORCID: https://orcid.org/0000-0001-5519-4031)
- Guy Laiguillon
- Graziella Matesic (ORCID: https://orcid.org/0000-0003-1124-8426)
- Miguel Taillepierre
- Marc Romana (ORCID: https://orcid.org/0000-0002-8715-9836)
- Cécile Masson (ORCID: https://orcid.org/0000-0001-7870-7821)
- Thierry Peyrard (ORCID: https://orcid.org/0000-0002-7715-568X)
- Jean‐Christophe Gelly (ORCID: https://orcid.org/0000-0001-5138-361X)
- Émilie Le Toriellec
- Caroline Le Van Kim (ORCID: https://orcid.org/0000-0002-3251-1310)
- Dawei Chen (ORCID: https://orcid.org/0000-0002-3405-6753)
- Romain Duval (ORCID: https://orcid.org/0000-0002-5785-0685)
- Alissa Soudry (ORCID: https://orcid.org/0009-0008-8261-989X)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Justus-Liebig-Universität Gießen (DE)
- Université Paris Cité (FR)
- Sorbonne Paris Cité (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Guangzhou Mechanical Engineering Research Institute (China) (CN)
- Guangzhou Blood Center (CN)
- Hôpital Robert-Debré (FR)
- Établissement Français du Sang (FR)
- Centre de Recherche Saint-Antoine (FR)
- Institut Cochin (FR)
- Centre Hospitalier Universitaire Pointe-à-Pitre (GP)
- Sociedade Brasileira de Cardiologia (BR)
- Institut des Maladies Génétiques Imagine (FR)
Publication Details
- Journal
- Blood
- Published
- 2025-03-16
- DOI
- https://doi.org/10.1182/blood.2024026285
- Citations
- 3
- Primary Topic
- Blood disorders and treatments
- Type
- article
- Field-Weighted Citation Impact
- 5.45