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Background: Sickle cell disease (SCD) patients undergo multiple red blood cell (RBC) transfusions and are regularly exposed to low-prevalence (LP) antigens specific to individuals of African descent. This study evaluated the prevalence of antibodies against LP antigens in SCD patients and the need to identify these antibodies in everyday practice., Study Design and Methods: Plasma from 211 SCD patients was tested with RBCs expressing the following LP antigens: RH10 (V), RH20 (VS), RH23 (D W ), RH30 (Go a ), KEL6 (Js a ), and MNS6 (He)., Results: Nine LP antibodies were found in eight patients (3.8%): five anti-RH23, two anti-RH30, and two anti-MNS6. The exposure risk, calculated for each LP antigen, was below 3% per RBC unit, for all antigens tested. Thus, in this cohort of transfused SCD patients, the prevalence of LP antibodies was similar to that of antibodies against antigens of the FY, JK, and MNS blood group systems. These findings also reveal the occurrence of anti-RH23 in SCD patients. No anti-RH20 or anti-KEL6 were found, despite the high frequency of mismatch situations., Conclusion: These results highlight the immunogenicity of these LP antigens, and the evanescence of antibodies against LP antigens. They also highlight the importance of appropriate pretransfusion testing for patients frequently transfused, who are likely to be exposed to multiple types of blood group antigens., (© 2018 AABB.)

Background: It has long been known that relative immunogenicity is a characteristic of protein red blood cell (RBC) antigens, but the mechanisms remain unclear. The aim of this work was to elucidate the mechanisms underlying this relative immunogenicity., Study Design and Methods: Two RBC antigens were used as a model--the highly immunogenic K antigen (KEL1) and the less immunogenic Fya antigen (FY1)--and analyzed the distribution of DRB1* molecules in two groups of Caucasian individuals producing anti-Fya (n = 29) or anti-K (n = 30) alloantibodies. These experimental results were compared to the results generated by TEPITOPE, a DRB1* peptide-binding motif prediction algorithm., Results: It was found that within the anti-Fya group, the DRB1*04 phenotypic frequency was 100 percent, indicating that the DRB1*04 molecule is the restriction molecule. In the anti-K group, numerous DRB1* molecules were identified, demonstrating a high degree of histocompatibility promiscuity, corresponding to the predominant molecules in the Caucasian population. These findings were confirmed by TEPITOPE., Conclusion: These results strongly suggest that protein RBC intrinsic immunogenicity depends on the distribution of DRB1* restriction molecules.

The Duffy antigen/receptor for chemokine (DARC) is an erythrocyte receptor for malaria parasites (Plasmodium vivax and Plasmodium knowlesi) and for chemokines. In contrast to other chemokine receptors, DARC is a promiscuous receptor that binds chemokines of both CC and CXC classes. The four extracellular domains (ECDs) of DARC are essential for its interaction with chemokines, whilst the first (ECD1) is sufficient for the interaction with malaria erythrocyte-binding protein. In this study, we elaborate and analyze structural models of the DARC. The construction of the 3D models is based on a comparative modeling process and on the use of many procedures to predict transmembrane segments and to detect far homologous proteins with known structures. Threading, ab initio, secondary structure and Protein Blocks approaches are used to build a very large number of models. The conformational exploration of the ECDs is performed with simulated annealing. The second and fourth ECDs are strongly constrained. On the contrary, the ECD1 is highly flexible, but seems composed of three consecutive regions: a small beta-sheet, a linker region and a structured loop. The chosen structural models encompass most of the biochemical features and reflect the known experimental data. They may be used to analyze functional interaction properties.

The mRNA for the Duffy blood group antigen, the erythrocyte receptor for the Plasmodium vivax malaria parasite, has recently been cloned and shown to encode a widely expressed chemokine receptor. Here, we show that the Duffy antigen/chemokine receptor gene (DARC) is composed of a single exon and that most Duffy-negative blacks carry a silent FY*B allele with a single T to C substitution at nucleotide -46. This mutation impairs the promoter activity in erythroid cells by disrupting a binding site for the GATA1 erythroid transcription factor. With the recent characterization of the FY*A and FY*B alleles, these findings provide the molecular basis of the Duffy blood group system and an explanation for the erythroid-specific repression of the DARC gene in Duffy-negative individuals.

Résumé: Les bases moléculaires de la plupart des antigènes des 33 groupes sanguins sont connues. Ces connaissances ainsi que l'accès à la technologie d'amplification génique (PCR) ont permis le développement des techniques de génotypage afin de prédire la présence ou l'absence d'antigènes de groupes sanguins à la surface des globules rouges. Le génotypage est requis lorsque les globules rouges d'un patient ne peuvent être utilisés en sérologie, soit du fait d'une transfusion récente, soit parce qu'ils sont recouverts d'autoanticorps. Plusieurs techniques de génotypage sont disponibles afin de déceler toute variation nucléotidique sur les gènes codant les antigènes de groupes sanguins. Elles ont évolué afin de répondre rapidement à l'urgence transfusionnelle et limiter le risque de contamination au sein d'un laboratoire de diagnostic moléculaire. Certaines technologies ont démontré leur capacité à réaliser le génotypage des antigènes de groupes sanguins à haut débit. Elles seront utilisées dans l'avenir pour établir une carte de groupes sanguins complète de chaque donneur mais, elles permettront aussi de détecter et de sélectionner des donneurs avec des phénotypes rares qui pourront alimenter la Banque nationale de sang de phénotype rare (BNSPR). [ABSTRACT FROM AUTHOR]