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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]

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]

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]

Background: Recent reports have indicated that the risk of anti-D alloimmunization following D-incompatible platelet (PLT) transfusion is low in hematology and oncology patients. We investigated the rate of anti-D alloimmunization in RhD-negative (D- ) patients with chronic liver disease transfused with D+ platelet concentrates (PCs) and the factors involved, at a liver transplant (LT) center.Study Design and Methods: We reviewed the blood bank database from January 2003 to October 2016. D- patients who had received D+ PLT transfusions were eligible if they had undergone antibody screening at least 28 days after the first D+ PC transfusion, had no previous or concomitant exposure to D+ blood products, and had not received anti-D immunoglobulins.Results: Six of the 56 eligible patients (10.7%) had anti-D antibodies. All had received whole blood-derived PCs. Four of 20 patients (20%) untransplanted or transfused before LT and only two of 36 patients (5.6%) transfused during or after LT produced anti-D antibodies. These two patients were on maintenance immunosuppression based on low-dose steroids and tacrolimus. The factors identified as significantly associated with anti-D immune response were the presence of red blood cell immune alloantibodies before D+ PLT transfusion (p = 0.003), and D+ PLT transfusion outside the operative and postoperative (5 days) periods for LT (p = 0.023).Conclusion: D- patients with chronic liver disease transfused with D+ PLTs before LT are at high risk of developing anti-D antibodies. Preventive measures should be considered for these patients. [ABSTRACT FROM AUTHOR]

Background: Partial D status is a major concern for transfusion and pregnancy, due to the possibility of carriers becoming immunized. When known carriers of a D variant have never been exposed to complete D, they are assumed to have D partial status based on the position of the amino acid substituted. New approaches for predicting immunization risk are required. We built a three-dimensional (3D) structural model to investigate the consequences of substitutions of Amino Acid 223 involved in a large number of D variants.Study Design and Methods: Homology modeling was performed with multiple templates. The model was evaluated by comparing the interactions of the known p.Phe223Val variant (RHD*08.01) and a new p.Phe223Ser variant (RHD*52) to RhD reference allele (p.Phe223). The consequences predicted by modeling the variants were compared with serologic data.Results: The 3D structural model was generated from two related protein structures and assessed with state-of-the-art approaches. An analysis of the interactions of the variant Residue 223 in the proposed 3D model highlighted the importance of this position. Modeling predictions were consistent with the serologic and clinical data obtained for the D antigen with a substitution of Amino Acid 223.Conclusion: We used a 3D structural model to evaluate the effect of the p.Phe223 substitution on the conformation of the RhD protein. This model shed light on the influence of substitutions on the structure of the RhD protein and the associated alloimmunization risk. These initial findings indicate that the p.Phe223Ser variant can be considered partial. [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]

Background Pneumococcal hemolytic uremic syndrome ( P- HUS) is a rare but severe complication of invasive pneumococcal disease ( IPD) in young children. Consensual biologic diagnosis criteria are currently lacking. Study Design and Methods A prospective study was conducted on 10 children with culture-confirmed IPD. Five presented with full-blown P- HUS, three had an incomplete form with hemolytic anemia and mild or no uremia ( P- HA), and two had neither HUS nor HA. Thomsen- Friedenreich ( T), Th, and Tk cryptantigens and sialic acid expression were determined on red blood cells (RBCs) with peanut ( PNA), Glycine soja (SBA), Bandeiraea simplicifolia II, and Maackia amurensis lectins. Plasma concentrations of the major endogenous T-antigen-binding protein, galectin-3 ( Gal-3), were analyzed. Results We found that RBCs strongly reacted with PNA and SBA lectins in all P- HUS and P- HA patients. Three P- HUS and three P- HA patients showed also concomitant Tk activation. Direct antiglobulin test ( DAT) was positive in three P- HUS (one with anti- C3d and two with anti- IgG) and two P- HA patients (one with anti- C3d and one with anti- IgG). RBCs derived from the two uncomplicated IPD patients reacted with PNA but not with SBA lectin. Gal-3 plasma concentrations were increased in all P- HUS patients. Conclusions The results indicate high levels of neuraminidase activity and desialylation in both P- HUS and P- HA patients. T-antigen activation is more sensitive than DAT for P- HUS diagnosis. Combining PNA and SBA lectins is needed to improve the specificity of T-antigen activation. High concentrations of Gal-3 in P- HUS patients suggest that Gal-3 may contribute to the pathogenesis of P- HUS. [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]

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]

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]

Background: Recent reports have indicated that the risk of anti-D alloimmunization following D-incompatible platelet (PLT) transfusion is low in hematology and oncology patients. We investigated the rate of anti-D alloimmunization in RhD-negative (D - ) patients with chronic liver disease transfused with D + platelet concentrates (PCs) and the factors involved, at a liver transplant (LT) center., Study Design and Methods: We reviewed the blood bank database from January 2003 to October 2016. D - patients who had received D + PLT transfusions were eligible if they had undergone antibody screening at least 28 days after the first D + PC transfusion, had no previous or concomitant exposure to D + blood products, and had not received anti-D immunoglobulins., Results: Six of the 56 eligible patients (10.7%) had anti-D antibodies. All had received whole blood-derived PCs. Four of 20 patients (20%) untransplanted or transfused before LT and only two of 36 patients (5.6%) transfused during or after LT produced anti-D antibodies. These two patients were on maintenance immunosuppression based on low-dose steroids and tacrolimus. The factors identified as significantly associated with anti-D immune response were the presence of red blood cell immune alloantibodies before D + PLT transfusion (p = 0.003), and D + PLT transfusion outside the operative and postoperative (5 days) periods for LT (p = 0.023)., Conclusion: D - patients with chronic liver disease transfused with D + PLTs before LT are at high risk of developing anti-D antibodies. Preventive measures should be considered for these patients., (© 2019 AABB.)