Immunohematology最新文献

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 Lu_null 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.

In pregnancy, D- pregnant women may be at risk of becoming immunized against D when carrying a D+ fetus, which may eventually lead to hemolytic disease of the fetus and newborn. Administrating antenatal and postnatal anti-D immunoglobulin prophylaxis decreases the risk of immunization substantially. Noninvasive fetal RHD genotyping, based on testing cell-free DNA extracted from maternal plasma, offers a reliable tool to predict the fetal RhD phenotype during pregnancy. Used as a screening program, antenatal RHD screening can guide the administration of antenatal prophylaxis in non-immunized D- pregnant women so that unnecessary prophylaxis is avoided in those women who carry a D- fetus. In Europe, antenatal RHD screening programs have been running since 2009, demonstrating high test accuracies and program feasibility. In this review, an overview is provided of current state-of-the-art antenatal RHD screening, which includes discussions on the rationale for its implementation, methodology, detection strategies, and test performance. The performance of antenatal RHD screening in a routine setting is characterized by high accuracy, with a high diagnostic sensitivity of ≥99.9 percent. The result of using antenatal RHD screening is that 97-99 percent of the women who carry a D- fetus avoid unnecessary prophylaxis. As such, this activity contributes to avoiding unnecessary treatment and saves valuable anti-D immunoglobulin, which has a shortage worldwide. The main challenges for a reliable noninvasive fetal RHD genotyping assay are low cell-free DNA levels, the genetics of the Rh blood group system, and choosing an appropriate detection strategy for an admixed population. In many parts of the world, however, the main challenge is to improve the basic care for D- pregnant women.

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.

This extraordinary case showcases the identification of a rare anti-En^a 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. En^a 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.

It has been reported that anti-A and anti-B (ABO antibody) titers decrease with age, but little is known about the association between ABO antibody titers and physiologic/biochemical parameters such as body mass index (BMI), gamma-glutamyl transpeptidase (GGT), and total cholesterol (T-Cho). We investigated the present situation of ABO antibody titers among healthy blood donors in Japan and the physiologic/biochemical factors that may be associated with changes in ABO antibody titers. Plasma from 7450 Japanese blood donors was tested for ABO antibody titers using ABO reverse typing reagents by an automated microplate system; donor samples were classified into low, middle, and high titers according to the agglutination results obtained with diluted plasma samples. Multivariate regression analysis was performed to analyze the association between ABO antibody titers and age, gender, biochemical parameters (alanine transaminase [ALT], GGT, globulin, T-Cho, and glycosylated albumin [GA]), and BMI according to the ABO blood groups. A significant correlation between ABO antibody titers and age/gender, except for gender in anti-A of blood group B donors, was observed. BMI showed significant but negative correlations with anti-A and anti-B (β = -0.085 and -0.062, respectively; p < 0.01) in blood group O donors. In addition, significant but negative correlations between GGT and T-Cho with anti-B of blood group A donors (β = -0.055 and -0.047, respectively; p < 0.05) were observed. Although differences existed among the ABO blood groups, ABO antibody titers seem to be associated with physiologic and biochemical parameters of healthy individuals.

Screening for clinically significant antibodies is crucial in transfusion medicine and is a routine part of pre-transfusion testing. The indirect antiglobulin test (IAT) is the most reliable and effective test for detecting clinically significant alloantibodies reacting at the antihuman globulin phase. Two of the main methods used for antibody detection and identification are solid-phase red cell adherence (SPRCA) and microcolumn agglutination technology (CAT), with or without enzyme-treated red blood cells (RBCs). This study was undertaken to detect and identify alloantibodies by performing antibody screen (ABS) and antibody identification (ABID) testing using SPRCA and CAT, with and without ficin-treated RBCs. Residual patient samples collected between 1 December 2020 and 19 May 2021 were saved, de-identified, and frozen at ≤-30°C before testing for alloantibodies. Seventy antibodies were detected in 53 samples among the 203 samples that underwent an ABS. Of those samples, 150 (73.0%) were nonreactive, 47 (23.1%) yielded positive results with both CAT and SPRCA, and six (3.0%) yielded positive ABS results with SPRCA only. Fifty-three samples that underwent ABID by both methods yielded eight samples with antibodies identified by SPRCA only. Additional enhancement of the CAT method by the use of ficin-treated RBCs was required to detect seven of the eight SPRCA-only antibodies; one sample remained nonreactive regardless. SPRCA testing detected clinically significant antibodies without the addition of enzyme-treated RBCs that was necessary in the CAT testing.

In sub-Saharan Africa, antibody detection tests remain inaccessible because of the high cost and limited shelf life of red blood cell (RBC) reagents. This study aimed at investigating the feasibility and performance of locally prepared RBC reagents for antibody detection in Burkina Faso. We conducted an experimental study comparing commercial RBC panels and a local panel prepared from phenotyped blood donors in Ouagadougou, Burkina Faso. Antibody detection testing was performed by the indirect antiglobulin test using a gel card filtration column in a low-ionic-strength solution. Judgment criteria were the concordance rate and the kappa agreement coefficient of results generated by the two panels. A total of 302 blood donors were phenotyped for the major antigens of the RH, KEL, MNS, FY, JK, LE, and P1PK blood group systems. From this pool of donors, we designed an RBC detection panel that was used to screen for unexpected antibodies in 1096 plasma samples from 832 patients with a history of transfusion and 264 recently delivered or pregnant women with no history of blood transfusion. A positive antibody detection test was observed in 8.1 percent of the samples using the local panel versus 6.4 percent with the commercial panels. A total of 23 samples were negative with the commercial panels and positive with the local panel, while the findings were reversed for four samples. The concordance rate was 97.5 percent, and the kappa agreement coefficient was 0.815. Our results suggest that the development of local RBC panels can be an alternative to commercial panels in countries with limited resources. It could also be a cost-effective intervention, mainly for children under 5 years of age, women of childbearing age, and pregnant women, all of whom are most at risk for malaria and sickle cell disease complications. Blood services could develop and implement appropriate strategies to make phenotyped donor pools available for the design of suitable RBC panels.