Meeting the transfusion needs of a patient with anti-Ena requires an international effort.

This extraordinary case showcases the identification of a rare anti-Ena specificity that was assisted by DNA-based red blood cell antigen typing and collaboration between the hospital blood bank in the United States, the home blood center in Qatar, the blood center Immunohematology Reference Laboratory, as well as the American Rare Donor Program (ARDP) and the International Society for Blood Transfusion (ISBT) International Rare Donor Panel. Ena is a high-prevalence antigen, and blood samples from over 200 individuals of the extended family in Qatar were crossmatched against the patient's plasma with one compatible En(a-) individual identified. The ISBT International Rare Donor Panel identified an additional donor in Canada, resulting in a total of two En(a-) individuals available to donate blood for the patient.

An update to Kidd blood group system.

Since publication of the original Immunohematology review of the Kidd blood group system in 2015 (Hamilton JR. Kidd blood group system: a review. Immunohematology 2015;31:29-34), knowledge has mushroomed pertaining to gene structure, alleles causing variant and null phenotypes, clinical significance in renal transplant and hemolytic disease of the fetus and newborn, and physiologic functions of urea transporters in non-renal tissues. This review will detail much of this new information.

Impact of transcription factors KLF1 and GATA1 on red blood cell antigen expression: a review.

KLF transcription factor 1 (KLF1) and GATA binding protein 1 (GATA1) are transcription factors (TFs) that initiate and regulate transcription of the genes involved in erythropoiesis. These TFs possess DNA-binding domains that recognize specific nucleotide sequences in genes, to which they bind and regulate transcription. Variants in the genes that encode either KLF1 or GATA1 can result in a range of hematologic phenotypes-from benign to severe forms of thrombocytopenia and anemia; they can also weaken the expression of blood group antigens. The Lutheran (LU) blood group system is susceptible to TF gene variations, particularly KLF1 variants. Individuals heterozygous for KLF1 gene variants show reduced Lutheran antigens on red blood cells that are not usually detected by routine hemagglutination methods. This reduced antigen expression is referred to as the In(Lu) phenotype. For accurate blood typing, it is important to distinguish between the In(Lu) phenotype, which has very weak antigen expression, and the true Lunull phenotype, which has no antigen expression. The International Society of Blood Transfusion blood group allele database registers KLF1 and GATA1 variants associated with modified Lutheran expression. Here, we review KLF1 and recent novel gene variants defined through investigating blood group phenotype and genotype discrepancies or, for one report, investigating cases with unexplained chronic anemia. In addition, we include a review of the GATA1 TF, including a case report describing the second GATA1 variant associated with a serologic Lu(a-b-) phenotype. Finally, we review both past and recent reports on variations in the DNA sequence motifs on the blood group genes that disrupt the binding of the GATA1 TF and either remove or reduce erythroid antigen expression. This review highlights the diversity and complexity of the transcription process itself and the need to consider these factors as an added component for accurate blood group phenotyping.

Histo-Blood Group Antigen-Producing Bacterial Cocktail Reduces Rotavirus A, B, and C Infection and Disease in Gnotobiotic Piglets.

The suboptimal performance of rotavirus (RV) vaccines in developing countries and in animals necessitates further research on the development of novel therapeutics and control strategies. To initiate infection, RV interacts with cell-surface O-glycans, including histo-blood group antigens (HBGAs). We have previously demonstrated that certain non-pathogenic bacteria express HBGA- like substances (HBGA+) capable of binding RV particles in vitro. We hypothesized that HBGA+ bacteria can bind RV particles in the gut lumen protecting against RV species A (RVA), B (RVB), and C (RVC) infection in vivo. In this study, germ-free piglets were colonized with HBGA+ or HBGA- bacterial cocktail and infected with RVA/RVB/RVC of different genotypes. Diarrhea severity, virus shedding, immunoglobulin A (IgA) Ab titers, and cytokine levels were evaluated. Overall, colonization with HBGA+ bacteria resulted in reduced diarrhea severity and virus shedding compared to the HBGA- bacteria. Consistent with our hypothesis, the reduced severity of RV disease and infection was not associated with significant alterations in immune responses. Additionally, colonization with HBGA+ bacteria conferred beneficial effects irrespective of the piglet HBGA phenotype. These findings are the first experimental evidence that probiotic performance in vivo can be improved by including HBGA+ bacteria, providing decoy epitopes for broader/more consistent protection against diverse RVs.

Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood.

Matching donor and recipient blood groups based on red blood cell (RBC) surface ABO glycans and antibodies in plasma is crucial to avoid potentially fatal reactions during transfusions. Enzymatic conversion of RBC glycans to the universal group O is an attractive solution to simplify blood logistics and prevent ABO-mismatched transfusions. The gut symbiont Akkermansia muciniphila can degrade mucin O-glycans including ABO epitopes. Here we biochemically evaluated 23 Akkermansia glycosyl hydrolases and identified exoglycosidase combinations which efficiently transformed both A and B antigens and four of their carbohydrate extensions. Enzymatic removal of canonical and extended ABO antigens on RBCs significantly improved compatibility with group O plasmas, compared to conversion of A or B antigens alone. Finally, structural analyses of two B-converting enzymes identified a previously unknown putative carbohydrate-binding module. This study demonstrates the potential utility of mucin-degrading gut bacteria as valuable sources of enzymes for production of universal blood for transfusions.

Haemolytic transfusion reactions caused by non-ABO red cell antibodies reported to the Norwegian Haemovigilance System 2004-2020.

BACKGROUND AND OBJECTIVES: The aim of this study was to analyse the reports received in the Norwegian Haemovigilance System from 2004 to 2020 on acute and delayed haemolytic transfusion reactions caused by non-ABO red cell antibodies. MATERIALS AND METHODS: Antibody specificity, clinical symptoms and outcomes were included when available. RESULTS: After transfusion of 3.7 million red cell concentrates, reports on 78 cases of haemolytic transfusion reactions caused by non-ABO red cell antibodies were received, corresponding to an incidence of 1 in 47,000 transfused red cell concentrates. There were 30 acute and 48 delayed haemolytic transfusion reactions. A total of 113 red cell antibodies were found: 82 alloantibodies, 6 autoantibodies and 25 cases where the antibody specificity could not be determined. Two fatalities occurred: one caused by anti-Wra and one caused by an unidentified red cell antibody. The most frequently reported antibody specificities were those in the Rh and Kidd blood group systems, representing 24% and 14%, respectively, of all the antibodies identified. In six cases, errors occurred, leading to the issuing of blood units without the required phenotype match. CONCLUSIONS: Despite the possible underreporting, the low number of serious haemolytic transfusion reactions reflects an adequate pre-transfusion practice by the Norwegian blood banks.

Blood donation screening for hepatitis B virus core antibodies: The importance of confirmatory testing and initial implication for rare blood donor groups.

BACKGROUND AND OBJECTIVES: Exclusion of blood donors with hepatitis B virus (HBV) core antibodies (anti-HBc) prevents transfusion-transmitted HBV infection but can lead to significant donor loss. As isolated anti-HBc positivity does not always indicate true past HBV infection, we have investigated the effectiveness of confirmatory anti-HBc testing and the representation of rare blood groups in anti-HBc-positive donors. MATERIALS AND METHODS: Three hundred ninety-seven HBV surface antigen-negative and anti-HBc initially reactive blood donor samples were tested by five different anti-HBc assays. RESULTS: Eighty percentage of samples reactive in Architect anti-HBc assay were positive by the Murex assay and anti-HBc neutralization. Eleven out of 397 samples showed discordant results in supplementary testing from the Murex confirmatory test result, and five remained undetermined following extensive serological testing. Thirty-eight percentage of anti-HBc-positive donors identified as minority ethnic groups compared with 11% representation in anti-HBc-negative donors (p < 0.0001); the frequency of the Ro blood group in anti-HBc-positive donors was 18 times higher in non-white ethnic groups. CONCLUSION: Using two anti-HBc assays effectively enabled the identification of HBV-exposed and potentially infectious donors, their deferral and potential clinical follow-up. However, the exclusion of confirmed anti-HBc-positive donors will still impact the supply of rare blood such as Ro.

A Rare Case of Hemolytic Disease of the Fetus and Newborn Caused by Anti-s Antibody in a Chinese Patient.

BACKGROUND: Anti-s is a rare alloantibody, and the reported cases of hemolytic disease of the fetus and newborn (HDFN) caused by anti-s are limited to non-Asian populations. METHODS: Here, we report the case of a Chinese woman with a history of multiple pregnancies who developed an alloantibody with anti-s specificity. RESULTS: Her newborn developed HDFN caused by anti-s but the clinical symptoms were not serious. After supportive treatment and bilirubin light phototherapy, the baby was discharged with a good prognosis. CONCLUSIONS: This is the first reported case of anti-s-induced HDFN in a Chinese patient, highlighting the need for further research in the Asian population.

The role of RBC antigen transgene integration sites on RBC biology in mice.

BACKGROUND: Transgenic mice expressing RBC specific antigens are widely used in mechanistic studies of RBC alloimmunization. Existing RBC donor strains have random transgene integration, potentially disrupting host elements that can confound biological interpretation. STUDY DESIGN AND METHODS: Integration site and genomic alterations were characterized by both targeted locus amplification and congenic backcrossing in the five most commonly used RBC alloantigen donor strains (KEL-K2hi , KEL-K2med , and KEL-K2lo , and KEL-K1). A targeted transgenic approach was developed to allow RBC specific transgene expression from a safe harbor locus (ROSA26). Alloimmune responses were assessed by transfusing alloantigen expressing RBCs into wild-type recipients and measuring alloantibodies by flow cytometry. RESULTS/FINDINGS: Four of the five analyzed strains had at least one gene disrupted by the transgene integration but none of the disrupted genes are known to be involved in RBC biology. The integration of KEL-K2med potentially altered the immunological properties of RBCs, although the biological significance of the observed changes is unclear. The ROSA26 targeted approach resulted in a single copy of the transgene that maintains RBC specific expression without random disruption of genomic elements. CONCLUSION: These findings provide a detailed characterization of genomic disruption by transgene integration found in commonly used RBC donor strains that is relevant to numerous previous publications as well as future studies. With the possible exception of KEL-K2med , transgene integration is not predicted to affect RBC biology in existing models, and new models can avoid this concern using the described targeted transgenic approach.

Assessment of Minor Blood Group System Antigens and Their Phenotype among Voluntary Blood Donors in Ethiopian Blood and Tissue Bank Service, Addis Ababa, Ethiopia.

Background: Red blood cell antigens are numerous in structural and functional diversity; some are proteins while others are carbohydrates. The international society of blood transfusion currently recognized 43 blood group systems containing 349 red cell antigens. It also acknowledged 9 blood group systems (ABO, Rhesus, Kell, Duffy, Kidd, MNS, P, Lewis, and Lutheran) that are clinically significant and associated with hemolytic transfusion reactions as well as hemolytic disease of fetuses and newborns. The objective of this study was to assess the distribution of minor blood group antigens and their phenotype among voluntary blood donors in Ethiopian blood and tissue bank service in Addis Ababa. Method: A cross-sectional study was conducted from January to March 2022 among 260 volunteer blood donors to determine minor blood group antigens and their phenotype at EBTBS, Addis Ababa, Ethiopia. Tests were performed using Galileo Neo Immucor, which is fully automated Immunohematology analyzer. Result: A total of 260 blood donors were screened of which 153 (59%) were males. The antigen frequencies of minor blood group systems were: Fy(a), Fy(b), Jk(a), Jk(b), k, S, s were 33.5%, 43.5%, 97.7%), 40.4%), 100%, 45%, 90%, respectively. Regarding phenotype distribution, the most common phenotypes were: Duffy Fy (a-b+) 36.9%, MNS S-s+ 55% and Kidd Jk (a+b-) 59.6%. Conclusion: This study highlights the frequencies of Fy(a), Fy(b), Jk(a), Jk(b), k, S and s blood group antigens and their phenotypes in volunteer blood donors at EBTBS, Addis Ababa. For the management of alloimmunization cases in transfused patients, knowledge of these minor blood group antigens is relevant.

Is it reasonable for the use of Rh-ee blood? A hospital-based survey from a southern medical center in Taiwan.

Identification of alloantibodies and achieving a reduction in the rate of red blood cell (RBC) alloimmunization are important issues to prevent transfusion complications. The aim of this study was to identify the antigen and alloantibodies in our patients and to study the association of alloimmunization with previous transfusion. Transfusion records from the blood bank of Kaohsiung Medical University Hospital between 2015 and 2017 were retrospectively enrolled in the study. Antigen and antibody identification was performed using routine blood bank methods. In total, 56,422 transfusion records from 2015 to 2017 were included in the study. Among them, 1858 alloantibody episodes were found in the pre-transfusion survey, and anti-Mia, anti-E, and cold antibodies were the most common alloantibodies, with a prevalence of 3.29% (1858/56,422). Among them, 130 episodes involved newly found alloantibodies with no alloantibodies found in the previous transfusion survey. Tracing back to these newly transfusion-induced alloantibodies, the antibody was found with a mean of 10.8 ± 7.8 units of packed RBC transfusion, a mean of 66.3 ± 52.8 days, and with a mean of 4.3 ± 2.7 times of transfusion from the first transfusion therapy. An antibody survey revealed that Rh-ee (62.1%) was the most common phenotype in these newly identified antibodies. In summary, this hospital-based study revealed that RBC alloantibody rates were present at rates of 3.29%, with anti-Mia, anti-E, and cold antibodies being the most common alloantibodies. Among them, anti-E was the most commonly developed alloantibody. Given that the Rh-ee group is the most common phenotype in our population, the strategy of using Rh-ee blood for Rh-ee recipients is reasonable for transfusion safety.

How to avoid the problem of erythrocyte alloimmunization in sickle cell disease.

Erythrocyte alloimmunization is a major barrier to transfusion in sickle cell disease (SCD) because it can lead to transfusion deadlock and the development of life-threatening hemolytic transfusion reactions (HTRs). Several risk factors have been identified, such as blood group polymorphism in these patients of African ancestry frequently exposed to antigens they do not carry and an inflammatory clinical state of the disease. The most important preventive measure is prophylactic red blood cell antigen matching, and there is a consensus that matching for Rh (D, C, E, c, e) and K antigens should be performed for all SCD patients. However, some patients are high responders and more at risk of developing antibodies and HTRs. For these patients, the extension of matching to other blood groups, including variant antigens of the RH blood group, the use of genotyping rather than serology to characterize significant blood groups, and the prophylactic administration of immunosuppressive treatments remain a matter of debate due to low levels of certainty concerning their effects and the difficulty of determining which patients, other than those already immunized, are at high risk. These issues were recently addressed by a panel of experts established by the American Society of Hematology. Here, we review and stratify the various interventions for preventing alloimmunization, based on the literature and our experience and taking into account the obstacles to their implementation and any future developments required.

The Role of Host Glycobiology and Gut Microbiota in Rotavirus and Norovirus Infection, an Update.

Rotavirus (RV) and norovirus (NoV) are the leading causes of acute gastroenteritis (AGE) worldwide. Several studies have demonstrated that histo-blood group antigens (HBGAs) have a role in NoV and RV infections since their presence on the gut epithelial surfaces is essential for the susceptibility to many NoV and RV genotypes. Polymorphisms in genes that code for enzymes required for HBGAs synthesis lead to secretor or non-secretor and Lewis positive or Lewis negative individuals. While secretor individuals appear to be more susceptible to RV infections, regarding NoVs infections, there are too many discrepancies that prevent the ability to draw conclusions. A second factor that influences enteric viral infections is the gut microbiota of the host. In vitro and animal studies have determined that the gut microbiota limits, but in some cases enhances enteric viral infection. The ways that microbiota can enhance NoV or RV infection include virion stabilization and promotion of virus attachment to host cells, whereas experiments with microbiota-depleted and germ-free animals point to immunoregulation as the mechanism by which the microbiota restrict infection. Human trials with live, attenuated RV vaccines and analysis of the microbiota in responder and non-responder individuals also allowed the identification of bacterial taxa linked to vaccine efficacy. As more information is gained on the complex relationships that are established between the host (glycobiology and immune system), the gut microbiota and intestinal viruses, new avenues will open for the development of novel anti-NoV and anti-RV therapies.

The human gut symbiont Ruminococcus gnavus shows specificity to blood group A antigen during mucin glycan foraging: Implication for niche colonisation in the gastrointestinal tract.

The human gut symbiont Ruminococcus gnavus displays strain-specific repertoires of glycoside hydrolases (GHs) contributing to its spatial location in the gut. Sequence similarity network analysis identified strain-specific differences in blood-group endo-ß-1,4-galactosidase belonging to the GH98 family. We determined the substrate and linkage specificities of GH98 from R. gnavus ATCC 29149, RgGH98, against a range of defined oligosaccharides and glycoconjugates including mucin. We showed by HPAEC-PAD and LC-FD-MS/MS that RgGH98 is specific for blood group A tetrasaccharide type II (BgA II). Isothermal titration calorimetry (ITC) and saturation transfer difference (STD) NMR confirmed RgGH98 affinity for blood group A over blood group B and H antigens. The molecular basis of RgGH98 strict specificity was further investigated using a combination of glycan microarrays, site-directed mutagenesis, and X-ray crystallography. The crystal structures of RgGH98 in complex with BgA trisaccharide (BgAtri) and of RgGH98 E411A with BgA II revealed a dedicated hydrogen network of residues, which were shown by site-directed mutagenesis to be critical to the recognition of the BgA epitope. We demonstrated experimentally that RgGH98 is part of an operon of 10 genes that is overexpresssed in vitro when R. gnavus ATCC 29149 is grown on mucin as sole carbon source as shown by RNAseq analysis and RT-qPCR confirmed RgGH98 expression on BgA II growth. Using MALDI-ToF MS, we showed that RgGH98 releases BgAtri from mucin and that pretreatment of mucin with RgGH98 confered R. gnavus E1 the ability to grow, by enabling the E1 strain to metabolise BgAtri and access the underlying mucin glycan chain. These data further support that the GH repertoire of R. gnavus strains enable them to colonise different nutritional niches in the human gut and has potential applications in diagnostic and therapeutics against infection.

Prevalence of COVID-19 among blood donors: The Jordan University of Science and Technology experience.

ABSTRACT: The corona virus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, had health and economic results that profoundly affected communities worldwide. Investigating the seroprevalence of SARS-Cov-2 in blood donors is of a significant clinical and scientific value as it adds to knowledge about local herd immunity levels.To study the prevalence of SARS-Cov-2 infection among blood donors at a tertiary referral hospital in the north of Jordan.This is a prospective study that included all blood donors between September 2020 and March 2021. Donors' IgG antibodies were qualitatively immunoassayed to determine the antibody status against SARS-CoV-2. The Elecsys Anti-SARS-CoV-2 technique was utilized.One thousand samples were tested by total antibody against SARS-CoV-2. The median age was 29 years, 96.7% were males. The seroprevalence was 14.5%, and 80% of the positive participants did not report previous COVID-19 infection. The seroprevalence of COVID-19 antibodies was less among smokers and those with an O blood group and higher among donors with an AB blood group.The prevalence of COVID-19 among healthy young blood donors at a tertiary teaching health facility in the north of Jordan was 14.5%. Smokers and those with an O blood group were less likely to be seropositive, as opposed to donors with an AB blood group.

Structural basis of P[II] rotavirus evolution and host ranges under selection of histo-blood group antigens.

Group A rotaviruses cause severe gastroenteritis in infants and young children worldwide, with P[II] genogroup rotaviruses (RVs) responsible for >90% of global cases. RVs have diverse host ranges in different human and animal populations determined by host histo-blood group antigen (HBGA) receptor polymorphism, but details governing diversity, host ranges, and species barriers remain elusive. In this study, crystal structures of complexes of the major P[II] genogroup P[4] and P[8] genotype RV VP8* receptor-binding domains together with Lewis epitope-containing LNDFH I glycans in combination with VP8* receptor-glycan ligand affinity measurements based on NMR titration experiments revealed the structural basis for RV genotype-specific switching between ßß and ßα HBGA receptor-binding sites that determine RV host ranges. The data support the hypothesis that P[II] RV evolution progressed from animals to humans under the selection of type 1 HBGAs guided by stepwise host synthesis of type 1 ABH and Lewis HBGAs. The results help explain disease burden, species barriers, epidemiology, and limited efficacy of current RV vaccines in developing countries. The structural data has the potential to impact the design of future vaccine strategies against RV gastroenteritis.

Alloimmunization in transfused patients with constitutional anemias in Norway.

BACKGROUND AND OBJECTIVES: The status of red blood cell alloimmunization in patients with constitutional anemias including hemoglobinopathies is not known in Norway. The study objective was to investigate the impact of a strategy based on phenotype-matching for C, c, E, e, K, Jka, Jkb, Fya, Fyb, S and s on alloimmunization. MATERIALS AND METHODS: We reviewed transfusions of 40 patients retrospectively using the computerized blood bank management system and medical records; including diagnosis, age at start of transfusion therapy, gender, number and age of packed red blood cell units transfused, follow-up time, phenotypes of the donors and patients, antigen-negative patients exposed to antigen-positive packed red blood cell units, transfusion reactions and alloantibody specificities. RESULTS: Forty patients received 5402 packed red blood cell units. Alloimmunization frequency was 20 % for the whole group, being 7%, 25 % and 30 % in patients with sickle cell disease (n = 14), thalassemia (n = 16) and other conditions (n = 10), respectively. The alloantibodies detected were anti-E, -c, -C, -Cw, -K, -Jka and -Lua. CONCLUSION: Good communication between the clinicians and the transfusion services is essential for successful management of patients with constitutional anemias. Providing full phenotype-matched units was not always possible. Extended pheno-/genotyping before the first transfusion and providing antigen-negative units for antigen-negative patients for at least C, c, E and K in every red cell transfusion would probably have reduced the alloimmunization rate. Non-phenotype-matched transfusions seem to be the main reason for alloimmunization. Finding markers for identifying responders prone to alloimmunization will ensure targeted transfusion strategies.

Effect of Infant and Maternal Secretor Status on Rotavirus Vaccine Take-An Overview.

Histo-blood group antigens, which are present on gut epithelial surfaces, function as receptors or attachment factors and mediate susceptibility to rotavirus infection. The major determinant for susceptibility is a functional FUT2 enzyme which mediates the presence of α-1,2 fucosylated blood group antigens in mucosa and secretions, yielding the secretor-positive phenotype. Secretors are more susceptible to infection with predominant rotavirus genotypes, as well as to the commonly used live rotavirus vaccines. Difference in susceptibility to the vaccines is one proposed factor for the varying degree of efficacy observed between countries. Besides infection susceptibility, secretor status has been found to modulate rotavirus specific antibody levels in adults, as well as composition of breastmilk in mothers and microbiota of the infant, which are other proposed factors affecting rotavirus vaccine take. Here, the known and possible effects of secretor status in both infant and mother on rotavirus vaccine take are reviewed and discussed.

Non-transfusion dependent thalassemia is independently associated with higher alloimmunization risk than transfusion dependent thalassemia and would benefit the most from extended red cell antigen-matching.

BACKGROUND: Alloimmunization prevalence is conventionally used to identify RBCs alloimmunization risk factors among thalassemia patients, but it may be confounded by differences in transfusion exposure especially between non-transfusion dependent thalassemia (NTDT) and transfusion dependent thalassemia (TDT) patients. To better identify thalassemia patients with high alloimmunization risks, we used cumulative incidence of first alloimmunization as a function of RBCs transfused to compare alloimmunization risks between TDT and NTDT and to evaluate other risk factors. We also proposed practical strategies to prevent alloimmunization in thalassemia. STUDY DESIGN AND METHODS: Adult TDT and NTDT patients who had received ≥2 transfusions and no alloimmunization before their first transfusion were included. Alloimmunization was defined as the development of clinically significant alloantibodies. We estimated the first alloimmunization incidence from transfusion by Kaplan-Meier analysis with the horizontal axis expressed as cumulative non-antigen-matched RBC units transfused. We compared this incidence between TDT and NTDT, and analyzed for other alloimmunization risk factors and the alloantibody specificities/frequencies. RESULTS: The alloimmunization prevalence was similar between TDT and NTDT (27% vs. 30% respectively, p = .726). However, for the same transfusion exposure, NTDT had higher alloimmunization incidence than TDT (hazard ratio 8.59, 95% confidence interval [2.25-32.74], p = .002), independent of age at first transfusion and last follow-up, gender, and splenectomy. Anti-E, anti-c, anti-Mia , and anti-Jka were most frequent. DISCUSSION: NTDT has the highest alloimmunization risk and would benefit the most from extended RBC antigen-matching, especially C, c, E, and e. Other blood group antigen-matching should be guided by the patient/donor disparities and alloantibody frequencies in different populations.