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BACKGROUND: Antibodies to Gerbich blood group antigens are exceedingly rare and can cause moderate transfusion reactions. Several deletional variants of the GE-gene, that harbors long sequence repeats, enable alloimmunization and formation of naturally occurring antibodies. SUBJECT AND METHODS: A female blood donor and soldier of the German Army without history of pregnancy or transfusion showed an antibody reactive with all test cells except for GE:-2-3 RBC. Thus, anti-Ge2 was suspected. Molecular analysis including fragment length specific PCR, Sanger sequencing and NGS should reveal the molecular background of the deficiency. Segregation of the variant alleles should be demonstrated by family analysis. RESULTS: Compound heterozygosity for GYPC exon 2 (GE*01.-02) and exon 3 (GE*01.-03) deletion was detected in the donor and her sister. The mother had one exon 3 amplicon of reduced length, while the father heterozygously exhibited a truncated GYPC exon 2. NGS clearly demonstrated reduced coverages within the deletional fragments within each family member. The donor and her sister showed the complete absence of a 640 bp fragment. DISCUSSION AND CONCLUSION: Rare GE deletion variants can induce naturally occurring anti-Ge2 in Caucasians. Because of an enhanced risk of injury as soldier autologous RBC of the donor were cryopreserved. The donor and her sibling can give blood for each other because of identical ABO, Rh, and K antigen blood types.
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Anemia Hemolítica Autoinmune , Antígenos de Grupos Sanguíneos , Humanos , Embarazo , Femenino , Donantes de Sangre , Antígenos de Grupos Sanguíneos/genética , Transfusión Sanguínea , Anticuerpos , FenotipoRESUMEN
BACKGROUND: The Er blood group system was recently shown to be defined by PIEZO1. The system consists of high prevalence antigens Era, Er3, ERSA, and ERAMA; and low prevalence antigen Erb. Era/Erb are antithetical with Er(a-b+) defined by the ER*B allele [c.7180G>A p.(Gly2394Ser)]. A nonsense variant c.5289C>G p.(Tyr1763*) is associated with a predicted Ernull phenotype, and a missense variant c.7174G>A p.(Glu2392Lys) in close proximity to p.2394 causes loss of both Era and Erb expression. STUDY DESIGN AND METHODS: We investigated PIEZO1 in four Er(a-) individuals who presented with anti-Era. Whole genome sequencing (WGS) and Sanger sequencing were performed. The location and structural differences of predicted protein changes were visualized using the predicted 3-D structure of Piezo1 created using AlphaFold2. RESULTS: One individual was homozygous for the reported ER*B. A second had a novel heterozygous nonsense variant c.3331C>T p.(Gln1111*), but a second allelic variant was not found. In the remaining two individuals, two different heterozygous novel missense variants, c.7184C>T p.(Ala2395Val) or c.7195G>A p.(Gly2399Ser), were in trans to the reported c.7180G>A variant, ER*B. AlphaFold2 protein modeling showed that each of the missense variants is predicted to encode an altered structural conformation near Era and Erb. CONCLUSIONS: Investigation of archived samples resulted in the identification of three novel PIEZO1 alleles including a predicted Ernull and two missense variants. Structural modeling suggests that the missense changes potentially alter Era/Erb epitope expression with p.2399Ser resulting in a small increase in the negative electrostatic potential.
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BACKGROUND AND OBJECTIVES: Serologic typing with monoclonal anti-D is mandatory for RHD antigen determination before transfusion, but due to aberrant (weak or partial) variants of RHD, results may be ambiguous and molecular RHD-typing is required. Before that, RHD-negative (RHD -) red blood cells concentrates (RBCs) shall be transfused to avoid anti-D formation, which probably leads to wastage of RHD - RBCs. STUDY DESIGN AND METHODS: All patients with ambiguous results in serologic RHD-typing and molecular RHD-typing were assessed retrospectively. The proportions of patients at risk for anti-D formation and the proportion of RHD - RBCs transfused unnecessarily were evaluated for the following transfusion strategies: (1) RHD-positive (RHD + )RBCs for all patients, (2) RHD + RBCs for patients with at least 2+ reaction with anti-D, (3) RHD + RBCs for patients with C and/or E in their RHCE-phenotype, (4) RHD + RBCs for patients with C and/or E and at least 2+ reaction, and (5) RHD - RBCs for all patients. RESULTS: A total of 112 patients were included. Most had weak D type 1-3 and a minority had other, rare RHD variants. The risk of anti-D formation was 4.5%, 2.9%, 1.8%, 1.0%, and 0% for strategies 1-5, respectively. The proportion of RHD - RBCs transfused unnecessarily was 0%, 49.5%, 0.9%, 50.5%, and 95.5%. CONCLUSION: Transfusing patients with a C and/or E in their RHCE-phenotype with RHD + RBCs resulted in a very low risk of immunization while avoiding wastage of RHD - RBCs. Therefore, this strategy should be used for some patients with ambiguous results in serologic RHD-typing and pending results of molecular RHD-typing.
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Antígenos de Grupos Sanguíneos , Sistema del Grupo Sanguíneo Rh-Hr , Humanos , Estudios Retrospectivos , Sistema del Grupo Sanguíneo Rh-Hr/genética , Transfusión Sanguínea , Fenotipo , Eritrocitos , Alelos , GenotipoRESUMEN
BACKGROUND: Transfusion of red blood cells (RBC) is an important component of treatment for myelodysplastic syndromes (MDS). Patients receiving frequent transfusions are more likely to develop alloimmunization, an immune reaction to minor RBC antigens that increases the risk of complications including delayed hemolysis. Phenotypic matching is believed to reduce alloimmunization although rigorous evidence is lacking. This study examines the association of alloimmunization with clinical and economic outcomes and may give insight into the potential benefit of phenotypic matching in MDS. STUDY DESIGN AND METHODS: This study used data from 1054 hospitals included in the Premier hospital chargemaster dataset. Alloimmunized MDS patients (January 2015 to June 2019) were indirectly identified by ICD-10 codes (antiglobulin crossmatch and RBC antibody identification). The primary objective was assessment of the association between incremental cost per patient encounter and alloimmunization in MDS patients. Secondary objectives were assessment of the association of length of stay, intensive care unit (ICU) admission, and inpatient mortality for alloimmunized versus non-alloimmunized MDS patients. RESULTS: Worse clinical and economic outcomes were observed for the alloimmunized group. Higher costs (14%), more ICU admissions (38%), longer hospital (21%) and ICU stays (55%), and greater mortality (30%) were observed among alloimmunized MDS patients compared to non-alloimmunized (p < .0001 for all comparisons). DISCUSSION: Alloimmunization may be associated with higher costs and greater risk of ICU admission and death in patients with MDS. While further mechanistic research is needed, it seems that MDS patients may benefit substantially from practices that limit risk of alloimmunization, including providing prophylactic antigen matching.
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BACKGROUND: Red cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and associated comorbidities. Despite prophylactic serological matching for ABO, Rh, and K, red cell alloimmunization persists, in part, due to a high frequency of variant RH alleles in patients with SCD and Black blood donors. STUDY DESIGN AND METHODS: We compared RH genotypes and rates of alloimmunization in 342 pediatric and young adult patients with SCD on chronic transfusion therapy exposed to >90,000 red cell units at five sites across the USA. Genotyping was performed with RHD and RHCE BeadChip arrays and targeted assays. RESULTS: Prevalence of overall and Rh-specific alloimmunization varied among institutions, ranging from 5% to 41% (p = .0035) and 5%-33% (p = .0002), respectively. RH genotyping demonstrated that 33% RHD and 57% RHCE alleles were variant in this cohort. Patients with RHCE alleles encoding partial e antigens had higher rates of anti-e identified than those encoding at least one conventional e antigen (p = .0007). There was no difference in anti-D, anti-C, or anti-E formation among patients with predicted partial or altered antigen expression compared to those with conventional antigens, suggesting that variant Rh on donor cells may also stimulate alloimmunization to these antigens. DISCUSSION: These results highlight variability in alloimmunization rates and suggest that a molecular approach to Rh antigen matching may be necessary for optimal prevention of alloimmunization given the high prevalence of variant RH alleles among both patients and Black donors.