Search

Background and Objectives: In Japan, the prevalence of haptoglobin deficiency is approximately 1 in 4000. Haptoglobin‐deficient individuals may produce anti‐haptoglobin from allo‐immunization, leading to serious transfusion reactions. Therefore, implementation of a consistent supply of haptoglobin‐deficient fresh frozen plasma is crucial. We developed a novel reagent to facilitate large‐scale identification of haptoglobin‐deficient individuals as potential donors of plasma products. Materials and Methods: We established mouse monoclonal anti‐haptoglobin‐producing cell lines (three clones) using the hybridoma method by immunizing mice with the haptoglobin protein. Purified antibodies were conjugated with carboxylate‐modified polystyrene latex beads and used for haptoglobin measurements by the latex agglutination method using an automatic analyser (LABOSPECT008). Samples with low protein concentrations were re‐examined by enzyme‐linked immunosorbent assay to confirm the results. Additionally, the haptoglobin gene was amplified by polymerase chain reaction to confirm the haptoglobin deletion allele (Hpdel). Results: From February to October 2022, 7476 blood donor samples were screened. Two haptoglobin‐deficient and 21 low‐haptoglobin‐expressing individuals were identified. Two haptoglobin‐deficient donors were found homozygous for Hpdel, and 19 (90%) of the 21 low‐haptoglobin‐expressing individuals were heterozygous for Hpdel, which includes the first reported case of heterozygous Hpdel/HpJohnson. Conclusion: We developed a new reagent for the detection of haptoglobin deficiency, which is automatable and inexpensive and appears useful for large‐scale screening of blood donors. [ABSTRACT FROM AUTHOR]

Background and Objectives: The Xg blood group is composed of two antigens, Xga (XG1) and CD99 (XG2 and MIC2). The XG and CD99 are homologous genes located on pseudoautosomal region 1 of the X and Y chromosomes. The expressions of Xga and CD99 are co‐regulated by a single nucleotide polymorphism (rs311103) in the GATA‐1 binding region. Another mechanism of the Xg(a−) phenotype is the genomic deletion of approximately 114 kb, including the XG gene. Anti‐Xga seems to be naturally occurring by detection in males who have never been transfused. Materials and Methods: In this study, we identified 23 anti‐Xga producers among 580,115 donors (0.004%). Additional 12 anti‐Xga producers were also identified from a separate cohort. Results: All 35 anti‐Xga producers were male. Genomic DNA was obtained from 34 of 35 producers, and all 34 producers were confirmed to carry the XG‐gene‐deficient allele (XGdel). The breakpoints of all 34 producers were identical. The XGdel was also identified in 12 non‐producers of anti‐Xga among 860 donors who have no antibodies against RBCs, and the breakpoints were also identical with the anti‐Xga producers. Conclusion: Our results will serve as the basis for a more complete understanding of Xg blood group polymorphisms. [ABSTRACT FROM AUTHOR]

Background: CD36 is a glycoprotein expressed on platelets and monocytes of the blood. There are two types of CD36 deficiency, type I and type II. Individuals with type I‐deficiency do not express CD36 in any cell type and can produce the CD36 antibody, which causes pathological conditions, such as fetal/neonatal alloimmune thrombocytopenia (FNAIT) and platelet transfusion refractory (PTR), through antigenic exposure via transfusion or pregnancy. Case presentation: We experienced a case of Philadelphia‐positive acute lymphoblastic leukaemia with PTR. In addition to the CD36 antibody, multiple‐specificity HLA antibodies were present in the patient's plasma, requiring transfusion of HLA‐compatible and CD36‐negative platelets (PC‐HLA). Since the number of donors was limited, it was necessary to set‐up a blood transfusion schedule so that hyper‐fractionated cyclophosphamide, vincristine and doxorubicin therapy (hyper‐CVAD) and ponatinib combination chemotherapy could be safely administered to achieve molecular remission. Rituximab administration resulted in reduced levels of both CD36 antibody and HLA antibody. Given the expression of CD36 on haematopoietic stem cells and the limited availability of CD36‐negative PC‐HLA, haematopoietic stem cell transplantation (HSCT) was not considered to be an option. Conclusion: If CD36‐negative, allogeneic haematopoietic stem cell donors are unable to be found, the indications for HSCT in patients with type I CD36‐deficiency should be carefully weighed. In the present case, molecular remission has been able to be maintained to the present day after completion of a two‐year maintenance regimen. [ABSTRACT FROM AUTHOR]

Background and Objectives: Antigens of the MNS blood group system are expressed on the red blood cell (RBC) membrane on glycophorin A (GPA) and glycophorin B (GPB) or on hybrid molecules of GPA and GPB. This study investigated the distribution of glycophorin variants and alloantibodies against Hil and MINY among Japanese individuals. Methods: Mi(a+) or Hil+ RBCs were screened using an automated blood grouping machine (PK7300) with monoclonal anti‐Mia or polyclonal anti‐Hil. Glycophorin variants were defined by serology with monoclonal antibodies against Mia, Vw, MUT and Mur, and polyclonal antibodies against Hil, MINY and Hop + Nob (KIPP). The glycophorin variants were further confirmed by immunoblotting and Sanger sequencing. Alloanti‐Hil and alloanti‐MINY in the plasma were screened using GP.Hil RBCs in an antiglobulin test. The specificity of anti‐Hil or anti‐MINY was assessed using GP.Hil (Hil+MINY+) and GP.JL (Hil‒MINY+) RBCs. Results: The GP.HF, GP.Mur, GP.Hut, GP.Vw, GP.Kip and GP.Bun frequencies in 1 005 594 individuals were 0·0357%, 0·0256%, 0·0181%, 0·0017%, 0·0009% and 0·0007%, respectively. GP.Hil was found in as four of the 13 546 individuals (0·0295%). Of 137 370 donors, 10 had anti‐Hil (0·0073%) and three had anti‐MINY (0·0022%). Conclusions: Glycophorin variants were relatively rare in Japanese individuals, with the major variants being GP.HF (0·0357%), GP.Hil (0·0295%) and GP.Mur (0·0256%). Only one example of anti‐MINY was previously reported, but we found three more in this study. [ABSTRACT FROM AUTHOR]

Background and Objectives: Efficiency in mitigating HIV transmission risk by transfusion may vary internationally. We compared HIV prevalence and incidence in blood donors across different jurisdictions in relation to those rates in the general population and differences in deferral practices. Materials and Methods: Data from 2007 to 2016 were collected in Australia, Brazil (São Paulo), Canada, England, France, Italy, Ireland, Japan, the Netherlands, New Zealand, Norway, Spain (Basque Country), USA (Vitalant) and Wales. For each country/region, the number of HIV antibody‐positive donations and nucleic acid testing (NAT)‐only‐positive donations was broken down according to first‐time or repeat donor status, along with the relevant denominators. Results: There is a modest correlation between HIV prevalence among first‐time donors and HIV prevalence in the general population. However, rates of HIV‐positive donations in repeat donors, a proxy for incidence, do not correlate with incidence rates in the general population. Rates in donors from Italy and Basque Country, where deferral criteria for men having sex with men are less stringent, are higher compared with most other jurisdictions. Rates of NAT‐only‐positive donations are extremely low and do not differ significantly after adjustment for multiple comparisons. Conclusion: Donor HIV rates are only weakly associated with those observed in the general population. Countries with less stringent deferral criteria have higher HIV rates in their donor population, but the rates remain very low. [ABSTRACT FROM AUTHOR]

Background: The low‐incidence antigen Sta of the MNS system is usually associated with the GP(B‐A) hybrid molecule, which carries the 'N' antigen at the N terminus. The GP(A‐A) molecule with trypsin‐resistant M antigen has been found in a few St(a+) individuals. Materials and Methods: Among Japanese blood donors, we screened 24 292 individuals for the presence of St(a+) with trypsin‐resistant 'N' antigen and 193 009 individuals for the presence of St(a+) with trypsin‐resistant M antigen. The breakpoints responsible for the Sta antigen were analysed by sequencing the genomic DNAs. Results: A total of 1001 (4·1%) individuals were identified as St(a+) with trypsin‐resistant 'N' antigen. Out of 1001 individuals, 115 were selected randomly for sequencing. Two novel GYP*Sch (GYP*401) variants with new intron 3 breakpoints of GYPA were detected in three cases. Twenty‐five (0·013%) individuals were identified as St(a+) with trypsin‐resistant M antigen. Five individuals had the GYP(A‐ψB‐A) hybrid allele; two of these five individuals were GYP*Zan (GYP*101.01), and the remaining three had a novel GYP(A‐ψB‐A) allele with the first breakpoint in GYPA exon A3 between c.178 and c.203. Nine individuals had a novel GYP(A‐E‐A) allele with GYPE exon E2 and pseudoexon E3 instead of GYPA exon A2 and A3. The 11 remaining individuals had a novel GYP(A‐A) allele with a 9‐bp deletion that included the donor splice site of intron 3 of GYPA. Conclusion: Our finding on diversity of glycophorin genes responsible for Sta antigen provides evidence for further complexity in the MNS system. [ABSTRACT FROM AUTHOR]

We found an individual with weakened S antigen expression on red blood cells (RBCs) during routine blood grouping. The proband was typed S+s+ by polyclonal antibodies, but the RBCs demonstrated different reactivity with three monoclonal anti‐S. The proband did not have alloanti‐S. Cloning and Sanger sequencing revealed that the proband had a c.166A>T (p.Thr56Ser) mutation in exon 4 of GYPB*S. When antibody screening of 60 455 blood donors was performed using the proband RBCs, no antibodies were detected. GYPB*S with c.166T should encode an unusual S antigen but the creation of a novel antigen remains to be investigated. [ABSTRACT FROM AUTHOR]

Malignant tumors are often associated with denervation, suggesting the functional implication of axonal guidance molecules in tumor growth. Here, we assessed the role of semaphorin 3 C (sema3 C) in the progression of gastric cancer. Immunohistochemistry of human samples revealed that sema3 C was strongly expressed in neoplastic cells, especially at the invasion front. Stable transfection of target sequences of sema3C mi RNA did not affect the in vitro proliferative activity of human gastric cancer AZ-521 cells. However, when the tumor growth was examined in vivo using an orthotopic model in nude mice, primary stomach tumors as well as metastatic liver tumors were significantly suppressed by sema3 C silencing with the reduction of microvessel density. Immunostaining of primary tumor indicated the rate of Ki-67 positive carcinoma cells was decreased, whereas that of apoptotic cells was significantly increased in sema3 C-silenced tumor. In addition, capillary-like tubular formation was reduced by the addition of culture media of sema3 C mi RNA cells compared with the media of control mi RNA cells. Semaphorin 3 C is positively expressed in gastric cancer cells and may be involved in tumor progression, presumably through the stimulation of angiogenesis. [ABSTRACT FROM AUTHOR]

Background: The XG blood group system comprises two antigens, Xg a and CD99. CD99 is known to be carried on both the X and Y chromosomes in pseudoautosomal region 1. We identified five unrelated Japanese individuals with anti-CD99 and investigated their genomic background as well as the clinical significance of anti-CD99., Study Design and Methods: Analysis of CD99 expression on RBCs and a modified monocyte monolayer assay was performed using flow cytometry. Genomic DNA was obtained from the five anti-CD99 producers to identify the deleted region responsible for the lack of CD99, and we conducted a long polymerase chain reaction using primer pairs specific for CD99 and GYG2., Results: CD99 expression from the Y chromosome was higher than that from the X chromosome. The five anti-CD99 plasma samples gave varied agglutination strengths with the red blood cells (RBCs) expressing high and low CD99 levels, in the antiglobulin test. The phagocytosis rate of anti-CD99-sensitized RBCs was 76.6% in one case indicating a risk of hemolytic transfusion reactions (HTR), and it correlated with the level of CD99 expression. The deleted region spanned 115 kb, from CD99 exon 3 to GYG2 exon 1. All five anti-CD99 producers were homozygous for the large deletion allele., Discussion: All five anti-CD99 producers were females with a history of pregnancy in Kyushu, Japan, and this deletion allele may thus be endemic. Our results indicated the possibility of HTR due to anti-CD99, and the risk is low when transfusing RBC products from Xg(a-) females with a low expression of CD99., (© 2025 AABB.)