Cardiac allotransplantation across major blood group barriers in the baboon

In heterotopic heart transplantation experiments in Chacma baboons, some of the animals were significantly immunosuppressed with cyclosporine, resulting in prolonged cardiac allograft survival. ABO blood group incompatibility between recipient and donor did not significantly influence mean allograft survival, but early hyperacute (vascular) or acute (cellular) rejection occurred only when ABO incompatibility was present.     

Frequencies of ABO, Rh and Kell phenotypes in couples from Han, Kazak, Uyghur and Hui in Xinjiang: an inheritance simulation model for blood group incompatibility in new-born

The Xinjiang region with residents from more than 13 minorities represents an area of many diverse ethnicities. This ethnic diversity in relation to their blood groups and immune status may have a consequential impact on the clinical status of married couples. To evaluate the risks of haemolytic disease in new-born infants, we investigated the rate of blood-group incompatibility among 487 married couples from four ethnic minorities, namely the Han, Hui, Uyghur and Kazak populations. Han minority married couples showed significantly different ABO, Rh and K phenotype frequencies between marrial relationship, whereas there was no significant difference in ABO, Rh and K phenotypes between the Uyghur, Hui and Kazak .There was a significant difference between ABO blood types in Han married couples, in the Kazak Rh-C phenotype and in the Uyghur Rh-D phenotype. The Hui married couples only demonstrated ABO, Rh and K phenotypes. The Hui minority showed the highest incompatibility rate for Rh-C and Rh-E phenotypes between mothers and their new-born infants. The highest incompatibility rate for the ABO phenotype occurred in the Kazak group. These results particularly demonstrate the clinical issues relating to ABO and Rh incompatibility, in the Kazak and Hui minorities, respectively.     

ABO hemolytic disease of the newborn as a selection mechanism at the ABO locus

Data from the period 1951 to 1967 were collected from the records at the Milwaukee Blood Center on 380 cases of ABO hemolytic disease to determine if ABO incompatibility may be regarded as a selection mechanism at the ABO locus. In comparison with infants of ABO compatible parents the affected infants had significantly lower hemoglobin and hematocrit values and higher bilirubin concentrations. Forty-eight percent of the affected showed a positive direct antiglobulin test, 81% showed increased numbers of reticulocytes and 92% had spherocytosis. Since affected infants are considered to be in grave danger when high concentrations of bilirubin are present it is significant that 169 individuals (44%) required exchange transfusions. Compared with the number of live births in Milwaukee for the same period this represents a frequency of one in every 1,654 live births so that ABO incompatibility may be regarded as an important mechanism of natural selection. Since it was found that 98.7% of the mothers of the affected infants are of blood group O, the affected infants are therefore heterozygous (AO or BO) and selection due to ABO incompatibility would have its greatest effect upon the lowest allele frequencies in a population.     

Association of the ABO blood group with certain human diseases

Following the discovery of ABO blood group over 100 years ago, a variety of studies sought to determine whether different disease states are influenced by ABO inheritance. As oligosaccharide antigens, ABO blood group antigens are widely expressed on the membrane of red blood cells and tissue cells, as well as in the saliva and body fluid. It is by far the most important blood group system in human immunohematology and transfusion medicine. While, other than determining blood group phenotype, accumulating evidence indicates that ABO blood group is implicated in the development of a number of human diseases. This review mainly focuses on the association between ABO blood group and cardiovascular system risk, corona virus disease 2019 (COVID-19), affective disorders, allergic diseases, as well as cancers.     

Zur Kenntniss der antifermentativen,lytischen und agglutinierenden Wirkungen des Blutserums und der Lymphe

Following the discovery of ABO blood group over 100 years ago, a variety of studies sought to determine whether different disease states are influenced by ABO inheritance. As oligosaccharide antigens, ABO blood group antigens are widely expressed on the membrane of red blood cells and tissue cells, as well as in the saliva and body fluid. It is by far the most important blood group system in human immunohematology and transfusion medicine. While, other than determining blood group phenotype, accumulating evidence indicates that ABO blood group is implicated in the development of a number of human diseases. This review mainly focuses on the associ-ation between ABO blood group and cardiovascular system risk, corona virus disease 2019 (COVID-19), affective disorders, allergic diseases, as well as cancers.     

Maternal IgG anti-A and anti-B titres predict outcome in ABO incompatibility in the neonate

Hemolytic disease of newborn (HDN) is an alloimmune hemolytic disease which occurs due to red blood type incompatibility between mother and fetus. An AB blood type neonate was admitted to Shengjing hospital with severe anemia. Major crossmatch incompatibility was found with some random donors. Serological tests were administered to the neonate and his parents. The mother was B blood type, while the father was AB blood type. The neonate's direct antiglobulin test (DAT) was negative, but the elution test was positive with A₁ cell and negative with A₂ cell. Titers 64 anti-A₁ and 2 anti-A in the mother's serum were detected after treated by dithiothreitol (DTT). The mother's red cells showed a weak agglutination with anti-A under microscopy. The neonate was diagnosed with HDN. After phototherapy and A₂B red blood cell (RBC) transfusion, the neonate was discharged with a recovery of his hemoglobin and physiological index. This study describes a rare case of HDN caused by anti-A1 allo-antibodies.     

Bone marrow transplantation for leukemia and aplastic anemia: management of ABO incompatibility.

Between February 1971 and October 1980, 34 patients with leukemia or aplastic anemia received bone marrow transplants from HLA-identical siblings whose lymphocytes did not react in a mixed leukocyte culture. The donors of 10 patients were ABO-incompatible, and for five pairs the ABO incompatibility was major. Plasma exchanges followed by a red blood cell exchange transfusion reduced the anti-A titres to 1:4 or less in these patients. The ABO incompatibility had no adverse effect on the results of marrow transplantation. Twenty-two patients, including 16 of the 20 who received their transplant after Jan. 1, 1980, are still living. Seven of the 15 patients with acute leukemia have survived 89 to 466 days, and 4 of the 6 with chronic myelogenous leukemia (CML) have survived 117 to 545 days. Of the 13 patients with aplastic anemia, 11 are alive up to 8 years after transplantation. Marrow transplantation, when possible, is the treatment of choice for young patients with acute leukemia in remission and for patients with aplastic anemia. Marrow transplantation may also prove to be effective in patients with CML.     

Risk Factors for Graft Failure and Death following Geriatric Renal Transplantation

BackgroundPopulation aging is a major health concern in Asian countries and it has affected the age distribution of patients with end-stage renal disease (ESRD). As a consequence, the need for kidney transplantation in the geriatric population has increased, but the shortage of donors is an obstacle for geriatric renal transplantation. The aim of this study was to evaluate risk factors for graft failure and death in geriatric renal transplantation.MethodsKidney transplantations performed in a tertiary hospital in South Korea from May 1995 to December 2014 were retrospectively reviewed. Recipients younger than 60 years of age or who underwent other organ transplantations were excluded. The Kaplan-Meier method was used to assess patient and graft survival. A Cox regression analysis was used to evaluate risk factors for graft failure and patient death.ResultsA total of 229 kidney transplantation patients were included. Graft survival at 1, 5, and 10 years were 93.2%, 82.9%, and 61.2% respectively. Patient survival at 1, 5, and 10 years were 94.6%, 86.9%, and 68.8%, respectively. According to the Cox multivariate analysis, ABO incompatibility (hazard ratio [HR] 3.91, p < 0.002), DGF (HR 3.544, p < 0.004), CMV infection (HR 2.244, p < 0.011), and HBV infection (HR 6.349, p < 0.015) were independent risk factors for graft survival. Recipient age (HR 1.128, p < 0.024), ABO incompatibility (HR 3.014, p < 0.025), CMV infection (HR 2.532, p < 0.010), and the number of HLA mismatches (HR 1.425, p < 0.007) were independent risk factors for patient death.ConclusionKidney transplantation in the geriatric population showed good clinical outcomes. ABO incompatibility, DGF, CMV infection, and HBV infection were risk factors for graft failure and the recipient age, ABO incompatibility, CMV infection, and the number of HLA mismatches were risk factors for patient death in geriatric renal transplantation.     

Advances in ABO gene expression regulation

The ABO blood group system is vital to blood transfusion and organ transplantation. ABO antigens are the most important of all blood group antigens in clinical practice, and are not only present in red blood cells and platelets, but also in most secretions and epithelial tissues. ABO antigens are known to undergo drastic changes during the development, differentiation, and maturation of normal cells. Profound changes have also been documented in pathological processes such as tumorigenesis. To elucidate the molecular basis of how ABO genes are controlled in cell type specific expressions, such as normal cell differentiation or in cancer cells lacking A/B antigens, it is essential to understand the regulatory mechanisms of ABO gene expression. In this review, current knowledge concerning the regulatory mechanisms of ABO gene expression was summarized.     

Acuity of selective mechanisms operating on ABO, Rh, and MN blood groups

Selection in ABO, Rh, and MN blood groups was studied in 216 matings and their children in an endogamous population. Incompatibility status with respect to these three systems was considered simultaneously. There is no effect of incompatibility on number of pregnancies. Analysis of variance between groups confirms that prenatal loss is associated with incompatibility, and it is greater when the matings are incompatible for any two systems. There is no significant intergenerational change in ABO and Rh polymorphisms. Segregation analysis for the ABO system suggests that there is no significant difference in the proportion of A, B, and O children, based on the compatibility of the parents, while analysis for Rh-D system showed a segregation distortion which is not related to the known antigenic specificities (mother-child incompatibility).     

Phenomenon of indirect isoserological incompatibility in experimental transfusion research and its clinical significance

It has been established in experiments on dogs exposed to blood transfusions that if the animals are screened according to the cross-matching testing system and show as a result the lack of red blood cell agglutination, this does not provide evidence in favour of their complete isoserological compatibility. To confirm whether the animals are compatible, it is required to carry out 7 to 8 tests with other species. If the tests reveal red blood cell agglutination, blood transfusion is characterized by demonstrable isoserological incompatibility and the recipient dies. If the cross-matching with the other animals of the group is accompanied by red blood cell agglutination but the latter is absent in the testing of a particular animal pair, such a condition is designated as "indirect" incompatibility, since hemotransfusion in this animal pair is characterized by the manifestations of incompatibility. However, it is not so pronounced and the recipient can be saved by intensive care. The authors conclude that isoserological incompatibility has different grades of intensity and offer methods for the screening of animals for simulation of graver and facilitated grades of incompatibility. It is assumed that the clinical transfusiology also has grades of the severity of hemotransfusion-induced conflicts, particularly in cardiosurgery. The use of large amounts of donor's blood for extracorporeal circulation and making for large blood losses is very likely to entail isoserological incompatibility cases which may remain unrecognized because of the gravity of surgical intervention, provoking at the same time the postoperative acute heart failure.     

DNA immunization against tissue-restricted antigens enhances tumor immunity after allogeneic hemopoietic stem cell transplantation

Malignant relapse remains a major problem for recipients of allogeneic hemopoietic stem cell transplantation (HSCT). We hypothesized that immunization of allogeneic HSCT recipients against tissue-restricted Ags using DNA vaccines would decrease the risk of relapse without enhancing graft-vs-host disease (GVHD). Using the mouse B16 melanoma model, we found that post-HSCT DNA immunization against a single tumor Ag induces tumor rejection that is significantly greater than HSCT alone in a T cell-depleted MHC-matched minor Ag-mismatched allogeneic HSCT model (LP --> B6). In treatment models, post-HSCT DNA immunization provides significantly greater overall survival than the vaccine alone. Donor leukocyte infusion further enhances tumor-free survival, including in treatment models. There was no GVHD in HSCT recipients treated with DNA vaccination and donor leukocyte infusion. Further analysis demonstrated that these effects are dependent on CD8+ T cells of donor origin that recognize multiple epitopes. These results demonstrate that DNA immunization against tissue-restricted Ags after allogeneic T cell-depleted HSCT can induce potent antitumor effects without causing GVHD.     

Do ABO Blood Group Antigens Hamper the Therapeutic Efficacy of Mesenchymal Stromal Cells?

Investigation into predictors for treatment outcome is essential to improve the clinical efficacy of therapeutic multipotent mesenchymal stromal cells (MSCs). We therefore studied the possible harmful impact of immunogenic ABO blood groups antigens – genetically governed antigenic determinants – at all given steps of MSC-therapy, from cell isolation and preparation for clinical use, to final recipient outcome.We found that clinical MSCs do not inherently express or upregulate ABO blood group antigens after inflammatory challenge or in vitro differentiation. Although antigen adsorption from standard culture supplements was minimal, MSCs adsorbed small quantities of ABO antigen from fresh human AB plasma (ABP), dependent on antigen concentration and adsorption time. Compared to cells washed in non-immunogenic human serum albumin (HSA), MSCs washed with ABP elicited stronger blood responses after exposure to blood from healthy O donors in vitro, containing high titers of ABO antibodies. Clinical evaluation of hematopoietic stem cell transplant (HSCT) recipients found only very low titers of anti-A/B agglutination in these strongly immunocompromised patients at the time of MSC treatment. Patient analysis revealed a trend for lower clinical response in blood group O recipients treated with ABP-exposed MSC products, but not with HSA-exposed products.We conclude, that clinical grade MSCs are ABO-neutral, but the ABP used for washing and infusion of MSCs can contaminate the cells with immunogenic ABO substance and should therefore be substituted by non-immunogenic HSA, particularly when cells are given to immunocompentent individuals.     

安徽省宁国县畲族红细胞血型分布

调查１６０名安徽省宁国县畲族村民的ＡＢＯ、Ｒｈ、Ｐ、ＭＮ系统红细胞血型,结果显示ＡＢＯ血型表型频率分布为Ｏ（０．４６８７）〉Ｂ（０．２３７５）〉Ａ（０．２２５０）〉ＡＢ（０．０６８８）,基因频率ｐ＝０．１５００,ｑ＝０．１５７５,ｒ＝０．６９２５;Ｒｈ血型表型频率分布为ＣＣｄｅｅ（０．５３８５）〉ＣＣＤＥ（０．１６６７）〉ＣｃＤＥ（０．１４７４）〉ＣｃＤｅｅ（０．０９６１）〉ｃｃＤＥ（０．０３２１     

Selective mechanisms operating on ABO and MN blood groups with special reference to prezygotic selection

Abstract

There is evidence from diverse sources to indicate that ABO blood groups are subject to natural selection at various developmental stages. This paper reviews the findings on associations between ABO blood groups and diseases and on ABO incompatibility as a major cause of prenatal and perinatal selection; provides evidence for prezygotic selection in ABO blood groups; and discusses selection for heterozygotes in ABO blood groups and in MN blood groups. From the evidence examined, the author concludes that the principal mechanism which maintains the ABO blood groups acts during prenatal and perinatal periods in addition to prezygotic stages; that the effective result of associations between ABO blood groups and adult diseases seems to be small; and that the MN polymorphism is probably maintained by the advantage of heterozygotes, apparently limited to MN mothers.     

Dissection and molecular analysis of alloreactive CD8+ T cell responses in allogeneic haematopoietic stem cell transplantation

We applied a cDNA expression screening procedure with cryopreserved non-clonal CD8+ T cell populations (Lennerz et al., Proc. Natl. Acad. Sci. USA 102:16013-8, 2005) to the identification of candidate antigens for graft-versus-host disease (GvHD) and graft-versus-leukaemia (GvL) effects in allogeneic haematopoietic stem cell transplantation (allo-HSCT). In a patient–donor model system with HLA class I disparities, we identified an HLA-B*44 mismatch allele, HLA-B*4405, as the dominant target of alloreactive T cells expanded in vitro from donor peripheral blood mononuclear cells (PBMC). HLA-B*4405-reactive T cells were detectable after multiple in vitro stimulations in the patient’s post-HSCT PBMC. In a patient–donor model with full HLA compatibility, the major target antigen of donor lymphocytes stimulated in vitro with the respective patient’s pre-HSCT PBMC was restricted by HLA-A*0201 and was encoded by TRIM22-442 C, a newly detected polymorphic allele of the tripartite motif family member TRIM22 (synonym: STAF50), preferentially expressed in cells of the haematopoietic system. An arginine(R)-to-cysteine(C) exchange at position 442 generated an immunogenic T cell epitope equivalent to a minor histocompatibility antigen (mHag). TRIM22-442C-specific T cells persisted long-term in the patient’s post-HSCT PBMC. Approximately, 1.3% of Caucasians carry TRIM22.442 C in association with HLA-A*0201. In particular, the knowledge of a large and diverse panel of such mHags may be crucial for further improvement of donor selection and adoptive T cell transfer strategies. The procedure applied herein will help to accelerate and facilitate their identification.     

Association between the ABO locus and hematological traits in Korean

ABSTRACT: BACKGROUND: Recently, genomewide association studies identified a pleiotropic gene locus, ABO, as being significantly associated with hematological traits. To confirm the effects of ABO on hematological traits, we examined the link between the ABO locus and hematological traits in Korean population-based cohorts. RESULTS: Six tagging SNPs for ABO were analyzed with regard to their effects on hematological traits [white blood cell count (WBC), red blood cell count (RBC), platelet (Plat), mean corpuscular volume (MCV), and mean corpuscular haemoglobin concentration (MCHC)]. Linear regression analyses were performed, controlling for recruitment center, sex, and age as covariates. Of the 6 tagging SNPs, 3 (rs2073823, rs8176720, and rs495828) and 3 (rs2073823, rs8176717, and rs687289) were significantly associated with RBC and MCV, respectively (Bonferroni correction p-value criteria < 0.05/6 = 0.008). rs2073823 and a reported SNP (rs8176746), as well as rs495828 and a reported SNP (rs651007), showed perfect linkage disequilibrium status (r2s = 0.99). Of the remaining 3 SNPs (rs8176720, rs8176717 and rs687289), rs8176717 generated an independent signal with moderate p-value (= 0.045) when it was adjusted for by rs2073823 (the most significant SNP). We also identified a copy number variation (CNV) that was tagged by the SNP rs8176717, the minor allele of which correlated with the deletion allele of CNV. Our haplotype analysis indicated that the haplotype that contained the CNV deletion was significantly associated with MCV (beta +/- se = 0.363 +/- 0.118, p =2.09 x 10-3). CONCLUSIONS: Our findings confirm that ABO is one of the genetic factors that are associated with hematological traits in the Korean population. This result is notable, because GWASs fail to evaluate the link between a CNV and phenotype traits.     

Maternal-fetal interaction in the ABO system: a comparative analysis of healthy mothers and couples with recurrent spontaneous abortion suggests a protective effect of B incompatibility.

We investigated the possible differential effects of A and B blood group materno-fetal incompatibility on human fertility through a comparative analysis of couples with recurrent spontaneous abortion (RSA) and healthy mothers. ABO phenotype was determined in 5180 healthy mothers and their newborn babies from the population of Sassari (Sardinia) and in 1359 healthy puerperae (women who have just given birth) from the population of Rome. Mother-newborn joint ABO distribution in healthy mothers was compared with wife-husband joint ABO distribution in RSA couples. Distortions from expected distribution were evaluated by symmetry analysis. In both RSA couples and healthy mothers significant deviation from expected symmetry patterns were observed. Deviations in RSA are in the opposite direction to those observed in healthy puerperae. The most important difference observed concerned the symmetric joint phenotypes mother (women) A/infant (husband) B (B incompatible) and mother (women) B/infant (husband) A (A incompatible). A low number of B incompatible in RSA couples and a high number of B incompatible in healthy mothers was observed. The phenomenon is much more evident in women aged 24-28 years, a period of maximum fecundity. It is possible that the presence of anti-B immunoglobulin in the mother might have a protective effect against fetal loss in some cases of mother-infant ABO incompatibility.     

ABO blood group and ischaemic heart disease in British men.

OBJECTIVE--To establish whether ABO blood group is related to ischaemic heart disease on an individual and geographic basis in Britain. DESIGN--Prospective study of 7662 men with known ABO blood group selected from age-sex registers in general practices in 24 British towns. MEASUREMENTS--ABO blood group, standard cardiovascular risk factors, social class, and presence or absence of ischaemic heart disease determined at entry to study. END POINTS--Eight year follow up of fatal and nonfatal ischaemic heart disease events achieved for 99% of study population. RESULTS--Towns with a higher prevalence of blood group O had higher incidences of ischaemic heart disease. In individual subjects, however, the incidence of ischaemic heart disease was higher in those with group A than in those with other blood groups (relative risk 1.21, 95% confidence limits 1.01 to 1.46). Total serum cholesterol concentration was slightly higher in subjects of blood group A. No other cardiovascular risk factor (including social class) was related to blood group. CONCLUSIONS--Blood group A is related to the incidence of ischaemic heart disease in individual subjects. Geographic differences in the distribution of ABO blood groups do not explain geographic variation in rates of ischaemic heart disease in Britain. The findings do not support the view that ABO blood group and social class are related.     

应用改良流式法检测猕猴和食蟹猴体内血型抗体水平的分布情况

绝大部分灵长类动物存在与人类相似的ABO血型系统,该研究采用改良流式法(flow cytometry method,FCM)检测猕猴及食蟹猴血清中血型抗体水平的分布情况。以流式细胞术为基础,使用商品化人源红细胞为靶细胞,并通过加入特异性荧光标记的抗人IgM或IgG二抗,对收集的实验用猕猴及食蟹猴的血清样本进行检测,以人类健康受试者的血清样本为对照,比较两者血型抗体水平的差异。结果显示:预先用人O型浓缩红细胞吸附猴血清中所含种属间非特异性抗体后,FCM法能够准确检测其血型抗体水平及分型,并且发现猴血清中天然血型抗体的水平明显低于健康人(P<0.05)。由此得出:通过预处理清除非特异性抗体的干扰后,FCM法同样适用于灵长类动物血清中血型抗体的检测,也为构建灵长类动物模拟人ABO血型不合器官移植模型提供了技术保障和实验数据。