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Summary: Delayed haemolytic transfusion reaction (DHTR) is a life‐threatening haemolytic anaemia following red blood cell transfusion in patients with sickle cell disease, with only scarce data in children. We retrospectively analysed 41 cases of DHTR in children treated between 2006 and 2020 in a French university hospital. DHTR manifested at a median age of 10.5 years, symptoms occurred a median of 8 days after transfusion performed for an acute event (63%), before surgery (20%) or in a chronic transfusion programme (17%). In all, 93% of patients had painful crisis. Profound anaemia (median 49 g/L), low reticulocyte count (median 140 ×109/L) and increased lactate dehydrogenase (median 2239 IU/L) were observed. Antibody screening was positive in 51% of patients, and more frequent when there was a history of alloimmunisation. Although no deaths were reported, significant complications occurred in 51% of patients: acute chest syndrome (12 patients), cholestasis (five patients), stroke (two patients) and kidney failure (two patients). A further transfusion was required in 23 patients and corticosteroids were used in 21 to reduce the risk of additional haemolysis. In all, 13 patients subsequently received further transfusions with recurrence of DHTR in only two. The study affords a better overview of DHTR and highlights the need to establish guidelines for its management in children. [ABSTRACT FROM AUTHOR]

Background: Many RhD variants associated with anti‐D formation (partial D) in carriers exposed to the conventional D antigen carry mutations affecting extracellular loop residues. Surprisingly, some carry mutations affecting transmembrane or intracellular domains, positions not thought likely to have a major impact on D epitopes. Study Design and Methods: A wild‐type Rh trimer (RhD1RhAG2) was modeled by comparative modeling with the human RhCG structure. Taking trimer conformation, residue accessibility, and position relative to the lipid bilayer into account, we redefine the domains of the RhD protein. We generated models for RhD variants carrying one or two amino acid substitutions associated with anti‐D formation in published articles (25 variants) or abstracts (12 variants) and for RHD*weak D type 38. We determined the extracellular substitutions and compared the interactions of the variants with those of the standard RhD. Results: The findings of the three‐dimensional (3D) analysis were correlated with anti‐D formation for 76% of RhD variants: 15 substitutions associated with anti‐D formation concerned extracellular residues, and structural differences in intraprotein interactions relative to standard RhD were observed in the others. We discuss the mechanisms by which D epitopes may be modified in variants in which the extracellular residues are identical to those of standard RhD and provide arguments for the benignity of p.T379M (RHD*DAU0) and p.G278D (RHD*weak D type 38) in transfusion medicine. Conclusion: The study of RhD intraprotein interactions and the precise redefinition of residue accessibility provide insight into the mechanisms through which RhD point mutations may lead to anti‐D formation in carriers. [ABSTRACT FROM AUTHOR]

Transfusions can be a life-saving treatment of patients with sickle-cell disease (SCD). However, availability of matched units can be limiting because of distinctive blood group polymorphisms in patients of African descent. Development of antibodies against the transfused red blood cells (RBCs), resulting in delayed hemolytic transfusion reactions (DHTRs), can be life-threatening and pose unique challenges for this population with regard to treatment strategies and transfusion management protocols. In cases where the transfused cells and the patient's own RBCs are destroyed, diagnosis of DHTR can be difficult because symptoms may mimic vaso-occlusive crisis, and frequently, antibodies are undetectable. Guidelines are needed for early diagnosis of DHTR because treatment may need to include temporarily withholding any new transfusions to avoid further hemolysis. Also needed are case-control studies to optimally tailor treatments based on the severity of DHTR and develop preventive transfusion strategies for patients at DHTR risk. Here, we will review gaps in knowledge and describe through case studies our recommended approach to prevent alloimmunization and to diagnose and treat symptomatic DHTRs for which complementary mechanistic studies to understand their pathogenesis are sorely needed. [ABSTRACT FROM AUTHOR]

Introduction: Blood group antigens of the RH system (formerly known as "Rhesus") play an important role in transfusion medicine because of the severe haemolytic consequences of antibodies to these antigens. No crystal structure is available for RhD proteins with its partner RhAG, and the precise stoichiometry of the trimer complex remains unknown. Methods: To analyse their structural properties, the trimers formed by RhD and/ or RhAG subunits were generated by protein modelling and molecular dynamics simulations were performed. Results: No major differences in structural behaviour were found between trimers of different compositions. The conformation of the subunits is relatively constant during molecular dynamics simulations, except for three large disordered loops. Discussion: This work makes it possible to propose a reasonable stoichiometry and demonstrates the potential of studying the structural behaviour of these proteins to investigate the hundreds of genetic variants relevant to transfusion medicine. [ABSTRACT FROM AUTHOR]

Abstract: Blood groups are clinically significant in sickle cell disease (SCD) as transfusion remains a key treatment in this pathology. The occurrence of a delayed haemolytic transfusion reaction (DHTR) is not rare and is a life-threatening event. The main cause of DHTR is the production of alloantibodies against red blood cell antigens. The high rate of alloimmunization in SCD patients is mainly due to the differences of red blood groups between patients of African descent, and the frequently Caucasian donors. From an immuno-haematological point of view, DHTR in SCD patients has specific features: classical antibodies known to be haemolytic can be encountered, but otherwise non significant antibodies, autoantibodies and antibodies related to partial and rare blood groups are also frequently found in individuals of African descent. In some cases, there are no detectable antibodies. As alloimmunization remains the main cause of DHTR, it is extremely important to promote blood donation by individuals of African ancestry to make appropriate blood available. [Copyright &y& Elsevier]

BACKGROUND: Weak D Types 1, 2, and 3 recipients cannot be immunized when exposed to D antigen. Molecular biology is very efficient to type weak D variants but rarely implemented in daily practice. The serologic typing practice of weak D in a Caucasian patient population was analyzed and a transfusion strategy is proposed. STUDY DESIGN AND METHODS: Samples typed either ddCcee or ddccEe in routine laboratories were tested with the indirect antiglobulin test (Du test). Du-positive samples were screened for weak D alleles Types 1, 2, and 3 and further tested with immunoglobulin M (IgM) anti-D reagents, used in a fully automated device. RESULTS: A total of 468 of 55,162 samples were found to be ddCcee or ddccEe. Ninety-three expressed weak D after the Du test leading to D+ assignment for transfusion. Seventy-three percent of Du-positive samples were weak D alleles Type 1, 2, or 3. Almost all weak D Types 1, 2, and 3 were positive with IgM reagents in gel matrix with an automated device. Other variants that could be potentially associated with anti-D alloimmunization, however, were also positive. CONCLUSION: Serology is very sensitive to detect weak D Types 1, 2, and 3, but there is no cutoff to distinguish variants of clinical significance. When molecular analysis is not available, it is proposed that a D+ status for blood recipients found to be weak D with a sensitive method be assigned, except for women of childbearing age or younger, because of the remaining possibility to be partial D or other rare weak D who can be immunized. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Antibodies against RH antigens are clinically significant. Some rare RH phenotypes, for example, RH:−46 (RN), RH:−18 (Hrs–), RH:−34 (Hrb–), and homozygous partial RH5 (e), are found exclusively in black persons of African descent. Quantitative and qualitative RHCE variants require characterization because the presence of these alleles can lead to difficulties when transfusion is needed. STUDY DESIGN AND METHODS: Here a new RH5 variant ( ceRA) in an Indian patient is described and investigated by serology (agglutination and flow cytometry analysis) and molecular and immunoblot analysis. RESULTS: Red blood cells (RBCs), typed as RH:-1,-2, -3,4,w5, expressed a very depressed RH5 antigen, with no expression of the RH19 (h) high-frequency antigen. Molecular analysis revealed a new Rhce allele (homozygous state), hereafter called ceRA. This new allele exhibited a G48C mutation in exon 1 and a G538C mutation in exon 4, predicting, respectively, a Trp16Cys substitution and a Gly180Arg substitution, both in the intramembranous domain of the Rhce polypeptide. Immunoblot analysis showed that this defect results in a dramatic loss of the amount of RHCE polypeptides within the RBC membrane. No reactivity was evidenced with most of anti-RH5, in agglutination as well as in flow cytometry techniques. CONCLUSION: Both serologic results and localization of the Gly180Arg substitution emphasize the risk of anti-RH5 alloimmunization for patients expressing this new allele ceRA at the homozygous state. These results point out the importance of obtaining blood donations for the frozen rare blood bank in case future transfusion is needed. [ABSTRACT FROM AUTHOR]

Background: D(C)(e) and D(C)e haplotypes may be encountered in the white population. Few data are available on the molecular backgrounds responsible for depressed expression of C and e.Study Design and Methods: Individuals of white origin carrying a D(C)(e) genotype resulting in depressed expression of C or both C and e were subdivided into two categories based on the RBC reactivity with the human sera Mol and Hor, which contain antibodies against low-frequency antigens of the Rh (RH) system and other non-Rh low-frequency antigens. Neither Hor+, Mol+ nor Hor+, Mol- RBCs expressed the V (RH10), VS (RH20), and/or Rh32 (RH32) low-frequency antigens. These results suggested that Hor+, Mol+ variants expressed Rh33 (RH33 or Har) and FPTT (RH50), whereas Hor+, Mol- variants might express an undefined low-frequency antigen. Further serologic and molecular analyses were performed.Results: Molecular analysis of Hor+, Mol+ variants revealed a hybrid gene structure RHCe-D(5)-Ce, in which exon 5 of RHCE (RHCe allele) was replaced by exon 5 of RHD (the so-called RHCeVA allele). The presence of exon 5RHD resulted in several amino acid alterations predicted in the external loop 4 of the CeVA polypeptide. Molecular analysis of Hor+, Mol- variants revealed the presence of a new RHCe allele characterized by a single point mutation C340T within exon 3 (the so-called RHCeMA allele), resulting in a R114W substitution predicted on the external loop 2 of the CeMA polypeptide. A serologic study showed a different pattern of reactivity with C and e MoAbs.Conclusion: Two types of mutations resulted in amino acid substitutions predicted in external loops 4 and 2, respectively, which altered both the C and e reactivity, and indicated conformation changes or defective interaction between nonadjacent loops of the Ce polypeptide. Serologic analysis showed that together with Hor and Mol sera testing, the use of different C and e MoAbs could help to identify these variants within the white population. [ABSTRACT FROM AUTHOR]

Six unrelated individuals of Afro-Caribbean origin, whose red cells have a marked reduction of the Rhe antigen expression, have been identified. All exhibited the same serological profile with anti-e monoclonal antibodies and lacked expression of the high frequency e-related antigen hrS. Transcripts and genomic analysis showed that these phenotypes resulted from the presence of two new RHCE alleles, ceMO and cEMI. The ceMO allele corresponded to a RHce gene carrying a G667T mutation (exon 5) and was detected at the homozygous state in sample 1 and at the heterozygous state in samples 2–6. The G667T mutation resulted in a Val223Phe substitution on the Rhce polypeptide, in close proximity to Ala226 (e-antigen polymorphism), which might account for the altered expression of e. The ceMO allele is also associated with the lack of expression of the hrS antigen. The absence of the hrS antigen expression may have implications in transfusion as hrS-negative individuals may develop clinically significant antibodies. The cEMI allele corresponded to a silent RHE allele carrying a nine nucleotide deletion within exon 3 and was detected at the heterozygous state in sample 2. This deletion resulted in a shortened polypeptide of 414 residues (instead of 417) that was absent (or severely reduced) at the red cell surface, as the E antigen was undetectable using serology and Western blot analysis with anti-E reagents. In DNA-based polymerase chain reaction genotyping for RHE determination, the cEMI allele provided a false positive result as the cells carrying this allele are serologically phenotyped as E-negative. The incidence of this allele in the Black population is unknown but, as shown already for D genotyping, one must exercise caution when genotyping is performed to detect the e/E polymorphism. [ABSTRACT FROM AUTHOR]

L'hémolyse post transfusionnelle retardée (HPTR) est une complication transfusionnelle redoutée dans la drépanocytose, elle est souvent associée à une allo immunisation qui restreint la transfusion. Dans ce contexte l'utilisation d'un traitement immunosuppresseur comme le rituximab (RTX) semble intéressant afin d'éviter la formation de nouveaux allo-anticorps après une transfusion. Dans cette étude rétrospective observationnelle nous rapportons les données de 60 administrations de RTX chez 45 patients drépanocytaires ayant des antécédents prouvés de HPTR avec allo-anticorps suivis à l'hôpital Henri Mondor. Nous avons recueilli les données médicales et biologiques et calculé le rendement transfusionnel à partir du nomogramme de Mékontso Dessap. Nous avons divisé les patients en deux groupes, le premier était constitué de patients ayant nécessité une transfusion dans un contexte d'intervention programmée ou dans un contexte d'urgence. À 30 jours de la transfusion, 62 % des cas n'avaient pas de HPTR, 17 % avait un HPTR intermédiaire et 7 % un HPTR biologique. Le second groupe comprenait des patients ayant un HPTR actif. À 30 jours de la transfusion 50 % des patients avaient un HPTR intermédiaire et 17 % un faible risque HPTR. Le RTX semble être efficace en prévention du HPTR chez les patients ayant un antécédent de HPTR avec allo-anticorps. L'efficacité semble moindre chez les patients en HPTR actif mais permet de passer le cap aigu de l'urgence. Les mesures adjuvantes (introduction d'Hydroxyurée, injection de Fer et d'EPO) permettent dans la majorité des cas une épargne transfusionnelle. Tous les patients transfusés ont eu des culots phénotypés élargis. [ABSTRACT FROM AUTHOR]

L'allo immunisation anti-érythrocytaire est le principal risque immunologique de la transfusion de concentrés de globules rouges. Les recommandations de la Haute Autorité de Santé préconisent de transfuser des CGR phénocompatibles pour les systèmes RH (D, C, E, c, e) et l'antigène Kell chez les patients polytransfusés, et plus à risque au décours des multiples expositions de développer des allo anticorps. Ces allo anticorps génèrent des impasses transfusionnelles et un risque d'hémolyse post transfusionnelle. C'est le cas pour les patients souffrant de syndromes myélodysplasiques et pour lesquels le support transfusionnel régulier est indispensable. Ces patients sont après ceux atteints d'hémoglobinopathies les populations les plus fréquemment immunisées. Ceci étant, la ressource en CGR phénocompatibles n'est pas toujours disponible, et surtout lorsque ces patients présentent un phénotype RH moins commun (exemples : D + C-E-c + e+, ou D + C-E + c + e-). La question peut donc légitimement se poser de savoir si la phénocompatibilité RH/K doit s'appliquer dans tous les cas. Les données de la littérature montrent que la phénocompatibilité RH/K permet de diminuer l'incidence des allo anticorps dans ces systèmes, mais des études plus récentes montrent aussi que dans certaines situations, chez des patients au pronostic vital réduit, on peut déroger à ce protocole, sans pour autant mettre en jeu la sécurité immunologique. [ABSTRACT FROM AUTHOR]

L'hémolyse post-transfusionnelle du patient drépanocytaire est un accident transfusionnel qui peut mettre en jeu le pronostic vital. Au cours de la drépanocytose, cet accident présente des caractéristiques particulières : il est retardé et d'autant plus sévère qu'il est précoce, il se manifeste par des symptômes de la maladie de type vaso-occlusif, une anémie profonde, des urines foncées. On parle souvent d'hyper hémolyse car le Tx d'Hb pré-transfusionnel peut descendre largement en dessous du tx pré-transfusionnel, une nouvelle transfusion peut exacerber l'hémolyse dont l'impact sur l'anémie est potentialisé par une réticulopénie fréquente. La principale cause est une allo immunisation favorisée par les différences entre groupes sanguins de donneurs d'origine européenne, et patients, d'origine afro-antillaise. La gravité de l'hémolyse, n'est pas en rapport avec le conflit immunologique déclenchant, et ce d'autant que dans 30 % des cas, il n'existe aucun anticorps détectable. Le complément joue un rôle pivot dans la physiopathologie de cet accident, via son activation par la voie classique, anticorps dépendante, mais aussi par la voie alterne. L'efficacité de l'Eculizumab est une preuve de l'implication du complément. Chez ces patients hémolytiques chroniques, l'hème libre et celui libéré au cours de l'accident hémolytique ont des interactions avec le complément et sont des facteurs d'aggravation du tableau clinico-biologique. La prévention de cet accident repose sur des protocoles transfusionnels basés sur des facteurs de risques, qui nécessitent de connaître l'historique, et sur des traitements suppresseurs de l'allo immunisation, chez les patients immunisés. [ABSTRACT FROM AUTHOR]

After testing red cells from 12 RhE variants with a panel of anti-E monoclonal antibodies (MoAbs), four patterns of reactivity were detected indicating that the MoAbs may recognize four distinct E epitopes designated epE1, epE2, epE3 and epE4. The variants were classified into four categories (cat EI to EIV) which carried epE1 and epE2, epE1 and epE4, epE1, epE3 and epE4, and all four epitopes, respectively. Molecular analysis of the transcripts and genomic DNA of the variants from cat EI, EII and EIII displayed three distinct genetic alterations. Cat EI variants exhibited a point mutation (T500A) in exon 4 of the RHCE gene that resulted in a Met167Lys substitution in the third extracellular loop of the RhcE protein. Cat EII variant carried a hybrid gene structure characterized by replacement of exons 1–3 (or 2–3) of the RHCE gene by their specific counterparts in the RHD gene. This latter variant was also associated with a weak expression of the RhC antigen. In cat EIII variants there was a partial DNA exchange of exon 5 sequences (nt 697 and 712) between the RHCE and the RHD genes, generating a hybrid Rh cE-D-cE protein carrying the Glu233 and Val238 substitutions. The serological and molecular studies of the RhE variants indicated that: (i) the RhE antigen is a mosaic composed of at least four epitopes and proline at position 226 is necessary but not sufficient for the full expression of the E antigen, (ii) the lack of RhE epitope(s) is associated with heterogenous molecular alterations of the RHCE gene, and (iii) amino-acids located on the third and fourth extracellular loops of the RhCE polypeptide are critical for some RhE epitopes expression. [ABSTRACT FROM AUTHOR]

Background: The Rhesus antigen Ew (ISBT designation 004 011) was first described in 1955. It is defined by a specific antibody, but its molecular genetic basis has not yet been resolved.Study Design and Methods: Two individuals serologically characterized to express the rare Rhesus antigen Ew were analyzed by sequencing of all 10 exons of the RHCE gene.Results: A nucleotide exchange at position 500 (T500A) resulting in a Met167Lys amino acid substitution was found in both individuals. Moreover, we show that an individual carrying the Ew antigen is capable to produce an alloantibody against the wild-type E antigen.Conclusion: The single-point mutation T500A in exon 4 of the RHCE gene is a molecular basis of the rare Rhesus antigen Ew. [ABSTRACT FROM AUTHOR]

The Rhesus antigen Ew (ISBT designation 004 011) was first described in 1955. It is defined by a specific antibody, but its molecular genetic basis has not yet been resolved. Two individuals serologically characterized to express the rare Rhesus antigen Ew were analyzed by sequencing of all 10 exons of the RHCE gene. A nucleotide exchange at position 500 (T500A) resulting in a Met167Lys amino acid substitution was found in both individuals. Moreover, we show that an individual carrying the Ew antigen is capable to produce an alloantibody against the wild-type E antigen. The single-point mutation T500A in exon 4 of the RHCE gene is a molecular basis of the rare Rhesus antigen Ew. [ABSTRACT FROM AUTHOR]

Background and Objectives: Most myelodysplastic syndromes (MDS) patients become red blood cell (RBC) transfusion‐dependent. Transfusing MDS patients with prophylactically RH‐KEL1 antigen‐matched (PAM) RBC units is recommended to avoid RBC allo‐immunization. D+C−E−c+e+, D+C−E+c+e− and D+C+E−c−e+ phenotypes are infrequent among French blood donors. To preserve infrequent phenotype RBC units for patients other than MDS, and to manage frequent phenotype RBC unit stocks, we let, for 1 year, higher‐risk non‐immunized chronically transfused MDS and acute myeloid leukaemia (AML) patients receive RBC transfusions matched only for D. Our objectives were to evaluate the impact of non‐PAM transfusions on the transfusion policy (which would be modified in case of RBC allo‐immunization) for frequent and infrequent phenotypes patients and to estimate the number of infrequent phenotypes RBC units that could be redistributed to other patients. Results: Ninety patients were enrolled. Thirty‐five patients had infrequent phenotypes, nine received only PAM RBC (143 units) and 26 PAM and non‐PAM RBC (415 and 532, respectively): none developed allo‐immunization. Fifty‐five patients had frequent RBC phenotypes, 34 received only PAM RBC (561 units) and three developed antibodies (2 non‐RH‐KEL1 and one anti‐E); 21 received PAM and non‐PAM RBC (436 and 109, respectively) and one developed allo‐immunization (unknown specificity). Our strategy enabled us to preserve 532 infrequent phenotypes RBC units: 216 D+C−E−c+e+, 33 D+C−E+c+e− and 283 D+C+E−c−e+ units, representing 48.8% of the total number of RBC units received by infrequent phenotypes patients during the study period. Conclusion: Allowing the transfusion of non‐PAM RBC in selected chronically transfused MDS and AML patients was feasible and enabled to redistribute infrequent phenotypes RBC units to other patients in need. [ABSTRACT FROM AUTHOR]

L’accès aux analyses de biologie moléculaire (génotypage des systèmes de groupes sanguins) est devenu plus facile avec les progrès techniques et l’utilisation de kits commerciaux permettant une standardisation. Elles restent onéreuses, réalisées dans des laboratoires dédiés et leur prescription doit représenter un bénéfice de sécurité transfusionnelle ou obstétricale. La sérologie reste la technique de référence de la majorité des analyses immunohématologiques, le génotypage représentant une alternative pour résoudre les difficultés sans solution en sérologie : – impossibilité de déterminer le phénotype dans les divers systèmes immunogènes (RH, KEL, FY, JK, MNS) par technique d’hémagglutination (polytransfusé, TDA positif, absence de réactifs commerciaux) ; – variants d’expression partielle ou faible dans certains systèmes (particulièrement dans le système RH), indication à adapter en fonction de l’origine du patient et des situations clinicobiologiques. Le génotypage est par ailleurs utilisé dans la surveillance obstétricale pour déterminer le phénotype RH ou KEL du fœtus sur un prélèvement sanguin maternel grâce à l’ADN fœtal circulant. Cette technique permet également de sélectionner des donneurs compatibles lorsque les réactifs sérologiques n’existent pas ou présentant des phénotypes rares pour constituer les panels permettant d’identifier les anticorps ou de confirmer les phénotypes chez des malades. Enfin, cette technique a des limites : un gène peut être présent dans le génome, mais ne pas s’exprimer à la surface de l’hématie et plusieurs sondes doivent parfois être utilisées, tenant compte de l’origine ethnique du sujet, du fait des nombreux variants d’un même antigène. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that ABO blood group may play a role in the immunopathogenesis of SARS‐CoV‐2 infection, with group O individuals less likely to test positive and group A conferring a higher susceptibility to infection and propensity to severe disease. The level of evidence supporting an association between ABO type and SARS‐CoV‐2/COVID‐19 ranges from small observational studies, to genome‐wide‐association‐analyses and country‐level meta‐regression analyses. ABO blood group antigens are oligosaccharides expressed on red cells and other tissues (notably endothelium). There are several hypotheses to explain the differences in SARS‐CoV‐2 infection by ABO type. For example, anti‐A and/or anti‐B antibodies (e.g. present in group O individuals) could bind to corresponding antigens on the viral envelope and contribute to viral neutralization, thereby preventing target cell infection. The SARS‐CoV‐2 virus and SARS‐CoV spike (S) proteins may be bound by anti‐A isoagglutinins (e.g. present in group O and group B individuals), which may block interactions between virus and angiotensin‐converting‐enzyme‐2‐receptor, thereby preventing entry into lung epithelial cells. ABO type‐associated variations in angiotensin‐converting enzyme‐1 activity and levels of von Willebrand factor (VWF) and factor VIII could also influence adverse outcomes, notably in group A individuals who express high VWF levels. In conclusion, group O may be associated with a lower risk of SARS‐CoV‐2 infection and group A may be associated with a higher risk of SARS‐CoV‐2 infection along with severe disease. However, prospective and mechanistic studies are needed to verify several of the proposed associations. Based on the strength of available studies, there are insufficient data for guiding policy in this regard. [ABSTRACT FROM AUTHOR]

• Transfusion protocols, in order to reduce alloimmunization, are well applied and efficient. • The prevalence of G6PD deficiency in transfused red blood cell units is important. • The G6PD deficiency is only found in red blood cell units from African ancestry blood donors. Transfusion has a central place in the treatment of patients with sickle cell disease (SCD). Matching blood groups of red blood cell (RBC) units with the blood groups of the patient is essential to prevent alloimmunization and delayed hemolytic transfusion reaction. African ancestry donors have the best phenocompatibility with patients of the same origin, however their RBCs may present characteristic that can alter quality of the unit such as glucose-6-phosphate dehydrogenase (G6PD) deficiency. The objective is to analyze transfusion protocol, immunization rate and mismatch situations of SCD recipients and to evaluate the frequency of G6PD deficiency in RBCs units from African ancestry donors. Samples of units transfused to SCD patients were analyzed. Transfusion data were collected from institutional databases. The activity of G6PD was measured in the segment of the RBC units. A total of 98 segments of units transfused to 37 SCD recipients in 41 transfusions episodes was collected. Among patients, 35.1% (n = 13) had no antibodies; 10.8% (n = 4) had antibodies against Fya/Fyb, Jka/Jkb, M/N, S/s; 21.6% (n = 8) against RH/K antigens. In all cases, the protocols were in line with the recommendations. G6PD deficiency was observed in 9 units, that were all collected from Afro-Caribbean donors. The transfusion protocol is established to prevent immunological reactions due to disparities in blood group antigens between donors and SCD recipients. However, the units of African ancestry donors, which allowed the best compatibility, displayed a high rate of G6PD deficiency. The storage and recovery impact of this deficiency must be evaluated. [ABSTRACT FROM AUTHOR]

The article discusses the discovery of a new RHCE*CE(c.382G>a) allele in patients of Asian ancestry, specifically in three female patients and one donor. The allele alters the expression of the E antigen and is associated with weak E or weak e typing. The novel allele has been provisionally assigned the designation RHCE*04.03 and may express partial antigens, requiring caution in transfusion scenarios. The findings highlight the importance of considering rare alleles in blood transfusion practices, especially in diverse populations. [Extracted from the article]

L’haplotype r’ S ou (C)ce S (1006)-ce S (1006) du système RH, fréquent chez les personnes d’origine afro-antillaise, induit un phénotype RH : − 1,2,−3,4,5,20. L’antigène RH2 (C) produit est partiel, et l’antigène RH20 (VS) est un antigène privé (spécificité absente du panel de RAI usuel). À l’état homozygote, cet haplotype produit le phénotype rare RH : − 31,−34 (hr B negatif). Des allo-immunisations post-transfusionnelles ou liées à la grossesse peuvent survenir : anti − RH2, −RH20 ou −RH34, considérées comme cliniquement significatives. Cette étude cible des donneurs de phénotype évocateur RH : − 1,2,−3,4,5 (100 % des drépanocytaires ayant ce phénotype ont un haplotype r’ S ), pour établir la prévalence de l’haplotype et rechercher le phénotype rare RH : − 31,−34. L’ADN de 175 donneurs métropolitains RH : − 1,2,−3,4,5 sans affaiblissement antigénique a été extrait et 2 PCR en temps réel (5’ nuclease assay ) ont été réalisées, à la recherche des polymorphismes associés à l’antigène RH2 (C) normal, et de la mutation c.1006G > T du gène RHCE , caractéristique de l’haplotype recherché. Chez 11 donneurs, la mutation c.1006G > T était présente et les polymorphismes de l’antigène RH2 (C) étaient absents, révélant un haplotype r’ S à l’état hétérozygote. Ainsi, 6,3 % des donneurs RH : − 1,2,−3,4,5 expriment l’antigène privé RH20, susceptible d’immuniser les receveurs (les patients drépanocytaires en particulier). La prévalence de l’haplotype est probablement encore plus élevée parmi les donneurs des DOM-TOM. Aucun sang rare RH : − 31,−34 n’a été mis en évidence parmi les 175 donneurs étudiés. Ces résultats permettent aussi d’estimer que 6,3 % des receveurs RH : − 1,2,−3,4,5 ont un antigène RH2 partiel non détecté. [ABSTRACT FROM AUTHOR]

Résumé non communiqué. [ABSTRACT FROM AUTHOR]

Background: Transfusion-transmitted bacterial infections (TTBIs) are the main residual infectious complications of transfusions. Escherichia coli and platelet (PLT) concentrates may be epidemiologically associated, leading to severe, if not lethal, TTBIs. We investigated the genotypic and phenotypic reasons for this clinically deleterious combination.Study Design and Methods: We investigated a French national E. coli strain collection related to six independent episodes of TTBIs. Their phenotypic characterizations included antibiotic susceptibility testing, growth testing under different culture conditions, serum survival assays, and virulence in a sepsis mouse model. Their genotypic characterizations included polymerase chain reaction phylotyping, whole genome sequencing, and a subsequent in silico analysis.Results: We highlighted a selection process of highly extraintestinal virulent strains, mainly belonging to the B2 phylogroup, adapted to the hostile environment (high citrate concentration and a bactericidal serum effect) of apheresis-collected platelet concentrates (PCs). Compared to controls, the E. coli TTBI strains grew faster in the PCs due to a superior ability to capture iron. The in vitro growth performances were highly compatible with blood-derived product real-life conditions, including storage conditions and delays. The consistent serum resistance of TTBI strains promotes their survival in both the donor's and the receiver's blood and in the PCs.Conclusion: This study pointed out that E. coli strains responsible for TTBI exhibit very specific traits. They belong to the extraintestinal pathogenic phylogroups and have a high intrinsic virulence. They can be resistant to complement, capture iron, and grow in the apheresis-collected PCs. These findings therefore support the reinforcement of the postdonation information. [ABSTRACT FROM AUTHOR]

RBC transfusion, immunohematology (RBC serology, blood groups), molecular biology Nucleotide changes or gene rearrangements can lead to RhD and/or RhCE proteins with qualitatively or quantitatively altered expression.1 ISBT lists more than 180 I RHCE i alleles. Keywords: immunohematology (RBC serology, blood groups); molecular biology; RBC transfusion EN immunohematology (RBC serology, blood groups) molecular biology RBC transfusion E59 E60 2 10/13/22 20221001 NES 221001 BACKGROUND Rh is the most complex of the red blood cell (RBC) blood group systems, comprising 56 antigens encoded by two homologous, closely linked genes, I RHD i and I RHCE i . [Extracted from the article]

Objectives: To determine the prevalence of red blood cell (RBC) alloimmunisation and alloantibody specificity in sickle cell disease (SCD) patients in Kisangani, Democratic Republic of Congo (DRC) in comparison with those followed at the Centre Hospitalier Régional (CHR) de la Citadelle of Liège (Belgium). Background: Data regarding RBC alloimmunisation (immune response of the organism to foreign erythrocyte antigens, antigens that lack on its own RBC) in SCD patients are scarce in sub‐Saharan Africa. Methods: We conducted a multi‐site‐based cross‐sectional study among 125 SCD patients at Kisangani and 136 at the CHR de la Citadelle of Liège. The diagnosis of SCD was confirmed by high‐performance liquid chromatography. Alloantibodies were screened using the agglutination technique on gel cards and their specificity determined using 11 and/or 16 cell panels. Statistical analyses were carried out using SPSS. Results: The prevalence of RBC alloimmunisation was 9.6% among SCD patients in Kisangani versus 22.8% in those of Liège. At Kisangani as well as at Liège, the median age of alloimmunised patients was higher than that of non‐alloimmunised patients, 15.5 years (IQR:4.8–19.8) and 24 years (IQR:14–31) versus 10 years (IQR: 6.5–17) and 17 years (IQR:12–24), respectively. The median number of blood units was higher in both Kisangani and Liège immunised patients compared to non‐immunised patients, 8 (IQR:5–11) versus 5 (IQR:3–13) and 41(IQR:6–93) versus 6.5(3–37) respectively. At Kisangani (N = 14), the most frequent antibodies were anti‐D (28.6%) and anti‐C versus anti‐E (13.6%), anti‐S (13.6%) and anti‐Lea (11.4%) at Liège (N = 44). Conclusions: These findings stated that alloimmunisation is a common complication in SCD patients in the DRC. In the resource‐limited setting of this country, blood transfusion with minimal ABO, D, C and E antigen matching in addition to the use of compatibility test could significantly reduce the incidence of this complication. [ABSTRACT FROM AUTHOR]

Background: Cerebral vasculopathy can induce chronic cerebral hypoperfusion leading to stroke in patients with sickle cell disease (SCD) and is treated by blood exchange transfusion (BET). However, no prospective clinical study has demonstrated the benefit of BET in adults with SCD and cerebral vasculopathy. Near Infrared Spectroscopy (NIRS) is a recent non-invasive method complementary to Magnetic Resonance Imaging (MRI). We evaluated cerebral perfusion using NIRS during erythracytapheresis in patients with SCD with and without steno-occlusive arterial disease. Methods: We conducted a monocentric, prospective study in 16 adults with SCD undergoing erythracytapheresis in 2014. Among them, 10 had cerebral steno-occlusive arterial disease. NIRS measured the relative amounts of oxyhemoglobin (OxyHb), deoxyhemoglobin (DeoxyHb) and total hemoglobin (Total Hb) in brain tissue and in muscle. Results: In cerebral hemispheres associated with steno-occlusive arterial disease, we observed a significant increase of OxyHb and Total Hb during BET, without modification of DeoxyHb. Conclusion: Using NIRS during BET showed that BET improves cerebral perfusion in adult patients with SCD with cerebral vasculopathy. [ABSTRACT FROM AUTHOR]

Des transfusions sanguines récurrentes sont indiquées dans de nombreuses pathologies du globule rouge. Dans ce contexte, la nécessité de réaliser des analyses sur les hématies se heurte à la présence de globules rouges (GR) de donneurs dans la circulation. En l'absence de tests à l'échelle unicellulaire, les résultats sont alors sous-estimés car ils reflètent une moyenne de la population totale. Nous avons mis au point une méthode de tri cellulaire permettant d'isoler les GR d'un patient transfusé afin de pouvoir les analyser en s'affranchissant des GR de donneurs. Le protocole transfusionnel d'un patient atteint de drépanocytose été adapté afin d'obtenir une différence antigénique entre les propres GR du patient (RhD +) et les GR des donneurs (RhD −). Ce protocole est déjà appliqué dans 40 % des cas de manière aléatoire, en fonction des ressources disponibles. Cette différence phénotypique permet le tri magnétique positif des GR du patient avec une pureté supérieure à 95 % (vérifiée par cytométrie en flux). Les propriétés biologiques des GR triés ont ensuite été analysées et comparées aux résultats obtenus sur les GR totaux. La population de GR triés montre des niveaux de stress oxydatif plus élevés que ceux observés sur GR totaux. La courbe d'association de l'oxygène montre un profil similaire à celui observé pour des patients non transfusés atteints de drépanocytose. Nos résultats montrent qu'une adaptation du phénotype des poches transfusées permet un tri et une analyse des propriétés biologiques des GR d'un patient transfusé. Ce tri représente un outil important en médecine personnalisée dans le but d'évaluer l'efficacité d'un traitement ou de préciser un diagnostic. [ABSTRACT FROM AUTHOR]

Background: There are two FDA‐approved anti‐CD38 monoclonal antibodies for treatment of multiple myeloma: isatuximab and daratumumab. Owing to expression of CD38 on reagent red blood cells (RBCs), these antibodies interfere with indirect antiglobulin tests (IATs). We sought to understand differences in such interference by performing binding experiments. Study Design and Methods: In vitro experiments to compare the binding to RBCs of isatuximab and daratumumab alone or in the presence of a mouse anti‐human CD38 antibody (HB‐7 or AT13/5) or a nicotinamide adenine dinucleotide‐analog CD38 inhibitor were performed and quantified by flow cytometry, imaging, mass spectrometry, surface plasmon resonance, and LigandTracer technologies. Serologic testing was performed on plasma samples spiked with isatuximab or daratumumab. Results: CD38 expressed on RBCs can be directly bound by daratumumab, whereas isatuximab requires a co‐factor, such as HB‐7, AT13/5, or a CD38 inhibitor, suggesting that the isatuximab epitope on RBCs is masked in vitro. Daratumumab samples more frequently showed interference and had stronger reactions than isatuximab samples. Dithiothreitol treatment was equally effective in mitigating the interference caused by either drug. Discussion: Both isatuximab and daratumumab interfere with IATs but at different magnitudes, reflecting distinct binding to CD38 on RBCs. From the binding studies, we conclude that the isatuximab epitope on RBCs is masked in vitro and binding requires a certain CD38 conformation or co‐factor. This circumstance may explain why interference is seen only in a subset of patients receiving isatuximab when compared with interference seen in most patients on daratumumab therapy. [ABSTRACT FROM AUTHOR]

Red blood cell transfusions have reduced morbidity and mortality for patients with sickle cell disease. Transfusions can lead to erythrocyte alloimmunization, however, with serious complications for the patient Includ-ing life-threatening delayed hemolytic trans-fusion reactions and difficulty in finding compatible units, which can cause transfu-sion delays. In this review, we discuss the risk factors associated with alloimmuniza-tion with emphasis on possible mecha-nisms that can trigger delayed hemolytic transfusion reactions in sickle cell disease, and we describe the challenges in transfu-sion management of these patients, includ-ing opportunities and emerging approaches for minimizing this life-threatening complica-tion. (Blood. 2012;120(3):528-537). [ABSTRACT FROM AUTHOR]

BACKGROUND: Minor histocompatibility antigens have been poorly defined. Whether Duffy (FY) and Kidd (JK), polymorphic and immunogenic blood group antigens, widely distributed in human organs, expressed and functional in the kidney, could function as minor histocompatibility antigens and be implicated in renal allograft rejection was questioned. STUDY DESIGN AND METHODS: A retrospective, homogeneous, single-center cohort of 370 renal transplants was analyzed. In all donor/recipient pairs, FY and JK polymorphisms were identified by real-time polymerase chain reaction. In all donor/recipient pairs the matching (m) or mismatching (mm) status was defined for both systems. All biopsies were reviewed, and historical screening results for FY and JK alloantibodies and graft survival were retrospectively analyzed. RESULTS: Although graft survival was not different between the groups, it was observed that FY mm grafts had significantly more chronic lesions compared to FY m grafts. HLA-DR11 was more frequent in both recipients (p = 0.0081) and donors (p = 0.0104) of FY mm couples without chronic allograft nephropathy, suggesting a protective effect for this molecule. JK mm grafts had more interstitial inflammation than JK m grafts (p = 0.0369). CONCLUSION: This renal model unmasks for the first time the role of FY and—to a lesser extent—JK antigens as minor histocompatibility antigens and suggests their potential role for other clinical transplant settings. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered virus for which remdesivir is the only antiviral available. We report the occurrence of a mutation in RdRP (D484Y) following treatment with remdesivir in a 76-year-old female with post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. A cure was achieved after supplementation with convalescent plasma. [ABSTRACT FROM AUTHOR]

Intraprotein interaction analysis predicted a single hydrophobic interaction for the consensus p.Phe111 residue, while the change to p.Leu111 was predicted to form one hydrophobic interaction with p.Leu115 and hydrogen bonds between main chains and p.Thr109, p.Ile113, p.Arg114, and p.Leu115. Abbreviation RBC red blood cells INTRODUCTION The D (RH1) antigen is a major antigen in immunohematology, both from a transfusion point of view due to its immunogenicity and polymorphism, but also from an obstetrical point of view. By the Biorad ID partial RhD typing set, the RBCs were non-reactive with LHM70/45, weakly reactive (1+ SP w sp ) with LHM59/19, and positive with all other clones (3+). [Extracted from the article]

Déterminer les paramètres âge, sexe, nombre et phénotype des PSL associés au risque d'allo-immunisation dans une population de patients homogènes quant aux caractéristiques des produits transfusés. Les paramètres étudiés ont été collectés sur la base des déclarations d'allo-immunisation anti-érythrocytaires déclarées en IdF entre 2012 et 2017. Le nombre et le phénotype des PSL transfusés avant la déclaration de l'allo-immunisation ont été repris dans la base Receveur de l'EFS IDF. Pour les immunisations RH/K, seuls ont été pris en compte les CGR phéno incompatibles dans ces systèmes. Pour les immunisations dans les autres systèmes, tous les CGR ont été comptabilisés, les phénotypes FY, JK, Ss n'étant pas connus pour ces CGR. Les patients ayant un anti-KEL1 et transfusés entre 2012 et 2017 ont été extraits de cette base pour valider les résultats des anticorps déclarés. Malgré l'absence de déclaration e-FIT dans plus de 50 % des cas et la difficulté d'exploiter des données hétérogènes en terme de saisie, cette étude confirme le rôle du nombre d'expositions aux antigènes de groupes sanguins comme facteur de risque d'immunisation anti-érythrocytaire, avec des immunisations rapides pour le RH/K, et une apparition plus tardive mais néanmoins précoce (5 CGR pour 50 % des allo immunisés) pour les autres systèmes. Ces données montrent que le statut de haut et bas répondeur des patients peut être rapidement connu, et le respect ou non du phénotype adapté en conséquence chez les patients de plus de 70 ans. Enfin, le risque d'allo immunisation vis-à-vis des antigènes mineurs (FY, JK, MNS) par exposition aux produits plaquettaires est faible (Tableaux 1, 2, 3). [ABSTRACT FROM AUTHOR]

Keywords: CCR7 receptor; CXCR4 receptor; whole blood; chemoattraction; red blood cell alloimmunization; Treg EN CCR7 receptor CXCR4 receptor whole blood chemoattraction red blood cell alloimmunization Treg 477 481 5 07/19/21 20210715 NES 210715 Understanding the mechanisms of the human immune response against red blood cell (RBC) antigens is a major issue for transfused patients.1,2 CD4 SP + sp T lymphocytes (TLs) play a key role in these reactions.3,4 Previously described by our group and others, several information are available about TL phenotypes and functions [regulatory T cells (Treg), T-helper cells type 17 (Th17) and follicular helper T cells (Tfh)],5-10 but little is known about the encounter of T cells with B cells leading to B-cell differentiation and antibody production in this context. Interleukin-6 receptor-alpha signaling drives anti-RBC alloantibody production and T-follicular helper cell differentiation in a murine model of red blood cell alloimmunization. (A) RBC alloantibody numbers in alloimmunized sickle cell disease (SCD) patients, and (B) RBC alloantibody specificities in these patients. [Extracted from the article]

Context: Sickle cell disease (SCD) is a severe hematological disorder. The most common acute complication of SCD is vaso-occlusive crisis (VOC), but SCD is a systemic disease potentially involving all organs. SCD prevalence estimates rely mostly on extrapolations from incidence-based newborn screening programs, although recent improvements in survival may have led to an increase in prevalence, and immigration could account for a substantial number of prevalent patients in Europe. The primary objective of this study was to estimate SCD prevalence in France. Methods: A cross-sectional observational study was conducted using a representative sample of national health insurance data. SCD patients followed up in France between 2006 and 2011 were captured through hydroxyurea reimbursement and with the International Classification of Diseases (ICD-10) SCD specific code D570.1.2, excluding code D573 (which corresponds to sickle cell trait (SCT)). Nevertheless, we assumed that ICD-10 diagnosis coding for inpatient stays could be imperfect, with the possibility of SCT being miscoded as SCD. Therefore, prevalence was analyzed in two groups of patients [with at least one (G1) or two (G2) inpatient stay] based on the number of SCD-related inpatient stays in the six-year study period, assuming that SCT patients are rarely rehospitalized compared to SCD. The prevalence of SCD in the sample, which was considered to be representative of the French population, was then extrapolated to the general population. The rate of vaso-occlusive crisis (VOC) events was estimated based on hospitalizations, emergencies, opioid reimbursements, transfusions, and sick leave. Results: Based on the number of patients identified for G1 and G2, the 2016 French prevalence was estimated to be between 48.6 per 100,000 (G1) or 32,400 patients and 29.7 per 100,000 (G2) or 19,800 patients. An average of 1.51 VOC events per year were identified, with an increase frequency of 15 to 24 years of age. The average annual number of hospitalizations was between 0.70 (G1) and 1.11 (G2) per patient. Intensive care was observed in 7.6% of VOC-related hospitalizations. Fewer than 34% of SCD patients in our sample received hydroxyurea at any point in their follow-up. The annual average cost of SCD care is €5,528.70 (G1) to €6,643.80 (G2), with most costs arising from hospitalization and lab testing. Conclusion: Our study estimates SCD prevalence in France at between 19,800 and 32,400 patients in 2016, higher than previously published. This study highlights the significant disease burden associated with vaso-occlusive events. [ABSTRACT FROM AUTHOR]

Background: Platelet (PLT) transfusions are an essential treatment for bleeding disorders. However, immunologic complications can occur, including alloantibody production against Class I HLA molecules. The principal source of HLA molecules in PLT concentrates (PCs) is the PLTs themselves. However, extracellular microparticles (MPs) present in PCs may express HLA molecules.Study Design and Methods: We used nanoscale flow cytometry to explore the expression of HLA-A2, HLA-B7, and HLA-B57 on the surface of cells, PLT-derived MPs (PMPs), lymphocyte-derived MPs (LMPs), and monocyte-derived MPs (MMPs) present in PCs. Expression was studied during 7 days of storage.Results: Platelets were not the only source of HLA molecules in PCs. HLA molecules were present on PMPs, LMPs, and MMPs. The level of HLA Class I molecule expression varied between haplotypes and MPs of different origins and during storage.Conclusion: Platelets or residual cells remaining after leukoreduction are not the only source of HLA Class I molecules in PCs, highlighting the contribution of MPs to alloimmunization mechanisms. These data may be relevant for the development of new transfusion guidelines. [ABSTRACT FROM AUTHOR]

Two prevalent ~100-kb GYPB deletions causative of the GPB-deficient blood group MNS phenotype S-s-U- in black Africans. The antigens of the MNS blood group system (ISBT002) are carried by glycophorin A and glycophorin B, encoded by I GYPA i and I GYPB i genes, respectively.1,2 A third gene, I GYPE i , located at the same 4q31.21 locus as I GYPA i and I GYPB i , does not express known antigens but participates in gene rearrangements.3 With 50 recognized antigens and over 50 alleles reported, including many hybrids, the MNS system is the second-most polymorphic and complex after RH. Multiple GYPB gene deletions associated with the U- phenotype in those of African ancestry. [Extracted from the article]

To the Editor, The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for coronavirus disease 2019 (COVID-19), has resulted in a global pandemic. COVID-19 occurring in patients with CVID has been reported in 5 patients and seems to confer an increased risk of severe COVID-19 [[2]]. In addition, for patient 2, mitogen-stimulated T cell proliferation was normal and SARS-CoV-2-specific T cell response evaluated by enzyme-linked immunoSpot (ELISPOT) was positive (Table 1) and similar to what is usually seen in non-ID patients with COVID-19 (data not shown). We describe the first two cases of severe COVID-19 in patients with hypogammaglobulinemia and absence of B lymphocytes and of efficacy of convalescent plasma in one patient with prolonged SARS-CoV-2 infection. [Extracted from the article]

Background: Patients with hematologic malignancies require prophylactic or curative platelet transfusions to prevent or treat bleeding. Treatments such as chemotherapy, radiotherapy, and hematopoietic stem cell transplantation cause persistent thrombocytopenia, necessitating platelet transfusions. However, class I HLA antibodies can cause a serious complication: immune‐mediated platelet refractoriness. The mechanisms of alloimmunization are incompletely understood. We explored the immunogenicity of HLA molecules and the phenotype of the HLA‐specific CD4+ T cells involved in alloimmunization. Study Design and Methods: We investigated the role of HLA molecules in platelet transfusion immunogenicity in a retrospective cohort study on men with specific anti‐HLA who had undergone transfusion. We investigated the presence and phenotypic profile of HLA‐specific CD4+ T cells in alloimmunized patients included in long‐term platelet transfusion programs for hematologic malignancies. Results: More than 50% of the transfused subjects displayed an antibody response against HLA‐B57 or ‐B58. HLA‐B57–specific CD4+ T‐cell responses were observed in patients alloimmunized against HLA‐B57. Following specific stimulation, the patients presented HLA‐specific CD4+ T cells producing tumor necrosis factor‐α, interleukin (IL)‐13, IL‐17A, IL‐2, IL‐10, and IL‐21. Conclusion: These results shed light on posttransfusion class I anti‐HLA alloimmunization mechanisms and constitute a first step toward developing new strategies for reducing refractoriness. [ABSTRACT FROM AUTHOR]

Background: CD36 glycoprotein is expressed by various cell types, including platelets (PLTs), monocytes, and erythroid precursors, and is also the receptor for several ligands. However, absence of CD36 expression seems asymptomatic and is poorly described in Caucasians. In contrast, the frequency reaches 7% and 11% in African Caribbean and Asian persons, respectively. Lack of CD36 expression exposes to the risk of immunization in case of pregnancy or PLT transfusion. Two types of deficiency have been described: in Type I, PLTs and monocytes lack CD36 expression and the subjects are homozygous or compound heterozygous for CD36 mutations, whereas in Type II, only PLTs (Type IIa), and rarely also erythroid cells (Type IIb), are affected. Molecular events leading to Type II deficiency are poorly understood. Case Report: An African girl, diagnosed with homozygous sickle cell disease and regularly transfused, was assessed for PLT CD36 expression by immunofluorescence microscopy. The deficiency was then confirmed by monoclonal antibody immobilization of PLT antigen (MAIPA) assay, and the subtype was assessed by flow cytometry. The underlying molecular basis was characterized by DNA sequencing. Furthermore, we tested the serum for possible anti‐CD36 immunization. Results and Conclusion: Flow cytometric analysis on the patient's blood samples allowed the diagnosis of Type I CD36 deficiency. CD36 antibodies, probably due to her past history of red blood cell transfusions, were identified by MAIPA and by Luminex technology assay. Interestingly, we identified through sequencing a new molecular basis involved in CD36 deficiency: two adenines were replaced by one guanine in Exon 4 (c.367_368delAAinsG) leading to a stop codon at Position 76. [ABSTRACT FROM AUTHOR]

Background: Blood transfusion is the cornerstone treatment to reduce the clinical severity of sickle cell disease (SCD), but we need to maintain the haematocrit (Hct) within an acceptable range to avoid a deleterious increase in blood viscosity. The aim of this study was to compare the effects of manual versus automated red blood cell (RBC) Exchange on haematological parameters and blood viscosity. Study design and methods: This prospective, single‐centre, open nonrandomized observational study included forty‐three sickle cell patients: 12 had automated RBC Exchange and 31 manual RBC Exchange. Samples were collected in EDTA tubes just before and within one hour after the end of the RBC Exchange to measure the haematological parameters and blood viscosity. Results: Both automated and manual RBC Exchange decreased haemoglobin S levels and leucocyte and platelet counts, but the decrease was greater for automated RBC Exchange. Manual RBC Exchange caused a significant rise in haematocrit and haemoglobin levels and did not change blood viscosity. In contrast, automated RBC Exchange decreased blood viscosity without any significant change in haematocrit and only a very slight increase in haemoglobin levels. The change in blood viscosity correlated with the modifications of haematocrit and haemoglobin levels, irrespective of the RBC Exchange procedure. When adjusted for the volume of RBC Exchange, the magnitude of change in each biological parameter was not different between the two procedures. Conclusion: Our study demonstrates that the automated RBC Exchange provided greater haematological and haemorheological benefits than manual RBC Exchange, mainly because of the higher volume exchanged, suggesting that automated RBC Exchange should be favoured over manual RBC Exchange when possible and indicated. [ABSTRACT FROM AUTHOR]

Depuis la découverte des bases moléculaires du système de groupe sanguin RH dans les années 1990, des centaines d'articles rapportent régulièrement de nouveaux allèles RH ainsi que des données hétérogènes : moléculaire, sérologique.. Les listes d'allèles existantes (Tables d'allèles de l'ISBT, site internet Rhesus Base), ne sont pas exhaustives et proposent très peu de fonctionnalités. Nous avons mis en place une base de données moderne, RHeference, basée sur BioDjango, un cadre de développement web en Python, contenant toutes les connaissances relatives aux allèles RHD, sans décalage du cadre de lecture, grâce à une revue exhaustive de la littérature scientifique. RHeference recense les bases moléculaires des allèles, les nomenclatures, l'expression des antigènes RH, les alloimmunisations associées décrites, le caractère faible ou partiel de l'antigène Rh1 (D).. L'origine de chaque information est indiquée dans la fiche de l'allèle, notamment la référence bibliographique de sa première description. RHeference permet une navigation aisée par requêtes pré-calculées : à partir de données moléculaires (mutations ou au contraire absence de mutations à certaines positions), par nom, par expression antigénique, par référence bibliographique. Des liens dédiés permettent de parcourir les données de manière transversale. Avec plusieurs centaines de références et 443 allèles, RHeference permet une vue d'ensemble des connaissances actuelles sur le gène RHD et a pour vocation à devenir son portail d'entrée principal. L'évolution de la base se fera par l'intégration des données scientifiques issues de la littérature, et de nouvelles fonctionnalités en lien avec la structure 3D. [ABSTRACT FROM AUTHOR]