International Society of Blood Transfusion Working Party on Red Cell Immunogenetics and Blood Group Terminology Report of Basel and three virtual business meetings: Update on blood group systems.

Background And Objectives: Under the ISBT, the Working Party (WP) for Red Cell Immunogenetics and Blood Group Terminology is charged with ratifying blood group systems, antigens and alleles. This report presents the outcomes from four WP business meetings, one located in Basel in 2019 and three held as virtual meetings during the COVID-19 pandemic in 2020 and 2021.

Materials And Methods: As in previous meetings, matters pertaining to blood group antigen nomenclature were discussed.

PIGG defines the Emm blood group system.

Emm is a high incidence red cell antigen with eight previously reported Emm- probands. Anti-Emm appears to be naturally occurring yet responsible for a clinically significant acute hemolytic transfusion reaction. Previous work suggests that Emm is located on a GPI-anchored protein, but the antigenic epitope and genetic basis have been elusive.

Novel variants in Krueppel like factor 1 that cause persistence of fetal hemoglobin in In(Lu) individuals.

Beta-hemoglobinopathies become prominent after birth due to a switch from γ-globin to the mutated β-globin. Haploinsufficiency for the erythroid specific indispensable transcription factor Krueppel-like factor 1 (KLF1) is associated with high persistence of fetal hemoglobin (HPFH). The In(Lu) phenotype, characterized by low to undetectable Lutheran blood group expression is caused by mutations within KLF1 gene.

Development and validation of a universal blood donor genotyping platform: a multinational prospective study.

Each year, blood transfusions save millions of lives. However, under current blood-matching practices, sensitization to non-self-antigens is an unavoidable adverse side effect of transfusion. We describe a universal donor typing platform that could be adopted by blood services worldwide to facilitate a universal extended blood-matching policy and reduce sensitization rates.

Transient and chronic childhood immune thrombocytopenia are distinctly affected by Fc-γ receptor polymorphisms.

In childhood immune thrombocytopenia (ITP), anti-platelet autoantibodies mediate platelet clearance through Fc-γ receptor (FcγR)-bearing phagocytes. In 75% to 90% of patients, the disease has a transient, self-limiting character. Here we characterized how polymorphisms of FcγR genes affect disease susceptibility, response to intravenous immunoglobulin (IVIg) treatment, and long-term recovery from childhood ITP.

Frequency and characterization of RHD variants in serologically D- Surinamese pregnant women and D- newborns.

Background: Numerous RHD variant genes affect the expression of D on the red blood cell surface. In Suriname, 4.3% of pregnant women were D-, ranging from virtually zero to 7% among ethnic groups.

Associations between single nucleotide polymorphisms and erythrocyte parameters in humans: A systematic literature review.

Individual variations in erythrocyte parameters are influenced by factors like sex, age, diet and season. Genetic variations have also been associated with erythrocyte parameters. The aim of this systematic review is to provide an overview of associations between single nucleotide polymorphisms (SNPs) and erythrocyte parameters in humans.

Performance evaluation study of ID RHD XT, a new genotyping assay for the detection of high-prevalence RhD negative and weak D types.

Background And Objectives: Routine serologic D typing does not distinguish between weak D subtypes and partial D phenotypes. The goal of this study was to validate the performance of the ID RHD XT genotyping assay.

Material And Methods: Previously serotyped samples for D antigen (n = 1000; 16% weak D serotyped donors) were analysed.

A Conceptual Framework for Optimizing Blood Matching Strategies: Balancing Patient Complications Against Total Costs Incurred.

Alloimmunization is currently the most frequent adverse blood transfusion event. Whilst completely matched donor blood would nullify the alloimmunization risk, this is practically infeasible. Current matching strategies therefore aim at matching a limited number of blood groups only, and have evolved over time by systematically including matching strategies for those blood groups for which (serious) alloimmunization complications most frequently occurred.

Performance evaluation study of ID CORE XT, a high throughput blood group genotyping platform.

Background: Traditionally, red blood cell antigens have been identified using serological methods, but recent advances in molecular biology have made the implementation of methods for genetic testing of most blood group antigens possible. The goal of this study was to validate the performance of the ID CORE XT blood group typing assay.

Materials And Methods: One thousand independent samples from donors, patients and neonates were collected from three research institutes in Spain and the Netherlands.

Validation of the multiplex ligation-dependent probe amplification assay and its application on the distribution study of the major alleles of 17 blood group systems in Chinese donors from Guangzhou.

Background: Genotyping platforms for common red blood cell (RBC) antigens have been successfully applied in Caucasian and black populations but not in Chinese populations. In this study, a genotyping assay based on multiplex ligation-dependent probe amplification (MLPA) technology was applied in a Chinese population to validate the MLPA probes. Subsequently, the comprehensive distribution of 17 blood group systems also was obtained.

Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis: prospective cohort study of a nationwide programme in the Netherlands.

Objective:  To determine the accuracy of non-invasive fetal testing for the RHD gene in week 27 of pregnancy as part of an antenatal screening programme to restrict anti-D immunoglobulin use to women carrying a child positive for RHD DESIGN:  Prospectively monitoring of fetal RHD testing accuracy compared with serological cord blood typing on introduction of the test. Fetal RHD testing was performed with a duplex real time quantitative polymerase chain reaction, with cell-free fetal DNA isolated from 1 mL of maternal plasma The study period was between 4 July 2011 and 7 October 2012. The proportion of women participating in screening was determined.

Identification of a novel frequent RHCE*ce308T variant allele in Chinese D- individuals, resulting in a C+c- phenotype.

Background: The RHCE allele is highly polymorphic; more than 60 variants have been described leading to diminished expression of C, c, E, and e antigens. Not much is known about the prevalence of RHCE variants in the Chinese population. Individuals carrying a variant are at risk to develop alloantibodies in response to mismatched pregnancy or transfusion.

Fetal RHD genotyping after bone marrow transplantation.

Background: Fetal RHD genotyping allows targeted diagnostic testing, fetal surveillance, and eventually intrauterine treatment to D-alloimmunized pregnant women who carry an RHD+ fetus. However, false-positive and false-negative results of noninvasive prenatal fetal RHD genotyping have been described due to a variety of causes. In this case report we present two cases where noninvasive fetal RHD typing was complicated by a previous bone marrow transplantation (BMT).

Prevalence of RhD status and clinical application of non-invasive prenatal determination of fetal RHD in maternal plasma: a 5 year experience in Cyprus.

Background: After the discovery that cell-free fetal DNA (cffDNA) is circulating in the maternal plasma of pregnant women, non-invasive prenatal diagnosis for fetal RhD in maternal plasma in RhD negative women at risk for haemolytic disease of the newborn (HDN) was clinically established and used by many laboratories. The objectives of this study are: (a) to assess the feasibility and report our experiences of the routine implementation of fetal RHD genotyping by analysis of cffDNA extracted from maternal plasma of RhD negative women at risk of HDN, and (b) to estimate the RhD phenotype frequencies, the RHD genotype frequencies and the RhD zygosity in the Cypriot population.

Methods: cffDNA was extracted from maternal plasma of 73 RhD negative pregnant women.

Frequency and characterization of known and novel RHD variant alleles in 37 782 Dutch D-negative pregnant women.

To guide anti-D prophylaxis, Dutch D- pregnant women are offered a quantitative fetal-RHD-genotyping assay to determine the RHD status of their fetus. This allowed us to determine the frequency of different maternal RHD variants in 37 782 serologically D- pregnant women. A variant allele is present in at least 0·96% of Dutch D- pregnant women The D- serology could be confirmed after further serological testing in only 54% of these women, which emphasizes the potential relevance of genotyping of blood donors.

Multiplex ligation-dependent probe amplification (MLPA) assay for blood group genotyping, copy number quantification, and analysis of RH variants.

The blood group multiplex ligation-dependent probe amplification (MLPA) is a comprehensive assay, developed for genotyping the majority of clinically relevant blood group antigens in both patients and donors. The MLPA is an easy method to apply and only requires a thermal cycler and capillary electrophoresis equipment. Because the molecular basis of blood group antigens can be a single nucleotide polymorphism, an insertion/deletion polymorphism, or genetic recombination, a single assay such as the MLPA to facilitate these different types of genetic variation is a prerequisite in blood group typing.

Novel alleles at the Kell blood group locus that lead to Kell variant phenotype in the Dutch population.

Background: Alloantibodies directed against antigens of the Kell blood group system are clinically significant. In the Netherlands, the KEL1 antigen is determined in all blood donors. In this study, after phenotyping of KEL:1-positive donors, genotyping analysis was conducted in KEL:1,-2 donors to identify possible KEL*02 variant alleles.

Molecular typing of human platelet and neutrophil antigens (HPA and HNA).

Genotyping is an important tool in the diagnosis of disorders involving allo-immunisation to antigens present on the membranes of platelets and neutrophils. To date 28 human platelet antigens (HPAs) have been indentified on six polymorphic glycoproteins on the surface of platelets. Antibodies against HPAs play a role in foetal and neonatal alloimmune thrombocytopenia (FNAIT), post-transfusion purpura (PTP) and refractoriness to donor platelets.