Augustine Blood Group System and Equilibrative Nucleoside Transporter 1

IF 1.9 4区 医学 Q3 HEMATOLOGY Transfusion Medicine and Hemotherapy Pub Date : 2021-12-07 DOI:10.1159/000520596
G. Daniels
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引用次数: 3

Abstract

Augustine (AUG) is a blood group system comprising four antigens: AUG1, AUG2 (Ata), and AUG4 are of very high frequency; AUG3 is of very low frequency. These antigens are located on ENT1, an equilibrative nucleoside transporter encoded by SLC19A1. AUG antibodies are of clinical relevance in blood transfusion and pregnancy: anti-AUG2 have caused haemolytic transfusion reactions; the only anti-AUG3 was associated with severe haemolytic disease of the fetus and newborn. ENT1 is present in almost all human tissues. It facilitates the transfer of purine and pyrimidine nucleosides and is responsible for the majority of adenosine transport across plasma membranes. Adenosine transport appears to be an important factor in the regulation of bone metabolism. The AUGnull phenotype (AUG:–1,–2,–3,–4) has been found in three siblings, who are homozygous for an inactivating splice-site mutation in SLC29A1. Although ENT1 is very likely to be absent from all cells in these three individuals, they were apparently healthy with normal lifestyles. However, they suffered frequent attacks of pseudogout, a form of arthritis, in various joints with multiple calcifications around their hand joints. Ectopic calcification in the hips, pubic symphysis, and lumbar discs was present in the propositus. The three AUGnull individuals had misshapen red cells with deregulated protein phosphorylation, but no anaemia or shortening of red cell lifespan. Defective in vitro erythropoiesis in the absence of ENT1 was confirmed by shRNA-mediated knockdown of ENT1 during in vitro erythropoiesis of CD34+ progenitor cells from individuals with normal ENT1. Nucleoside transporters, such as ENT1, are vital in the uptake of synthetic nucleoside analogue drugs, used in cancer and viral chemotherapy. It is feasible that the efficacy of these drugs would be compromised in patients with the extremely rare AUGnull phenotype.
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奥古斯丁血型系统与平衡核苷转运蛋白1
AUG1 (AUG2 (Ata))和AUG4是一个由四种抗原组成的血型系统,其中AUG1、AUG2 (Ata)和AUG4出现频率很高;AUG3的频率很低。这些抗原位于由SLC19A1编码的平衡核苷转运蛋白ENT1上。AUG抗体在输血和妊娠中具有临床意义:抗aug2已引起溶血性输血反应;唯一的抗aug3与胎儿和新生儿的严重溶血性疾病有关。ENT1几乎存在于所有人体组织中。它促进嘌呤和嘧啶核苷的转移,并负责大部分腺苷跨质膜的运输。腺苷转运似乎是调节骨代谢的一个重要因素。AUGnull表型(AUG: -1, -2, -3, -4)在三个兄弟姐妹中被发现,他们是SLC29A1剪接位点失活突变的纯合子。虽然这三个人的细胞中很可能都没有ENT1,但他们显然是健康的,生活方式正常。然而,他们经常遭受假性关节炎的袭击,这是一种关节炎,在他们的手关节周围有多种钙化。髋部、耻骨联合和腰椎间盘出现异位钙化。三名AUGnull个体的红细胞畸形,蛋白磷酸化失调,但没有贫血或红细胞寿命缩短。在来自正常ENT1个体的CD34+祖细胞的体外红细胞生成过程中,shrna介导的ENT1敲低证实了缺乏ENT1的体外红细胞生成缺陷。核苷转运体,如ENT1,在摄取用于癌症和病毒化疗的合成核苷类似物药物中至关重要。这是可行的,这些药物的疗效将损害患者极其罕见的AUGnull表型。
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来源期刊
CiteScore
4.00
自引率
9.10%
发文量
47
审稿时长
6-12 weeks
期刊介绍: This journal is devoted to all areas of transfusion medicine. These include the quality and security of blood products, therapy with blood components and plasma derivatives, transfusion-related questions in transplantation, stem cell manipulation, therapeutic and diagnostic problems of homeostasis, immuno-hematological investigations, and legal aspects of the production of blood products as well as hemotherapy. Both comprehensive reviews and primary publications that detail the newest work in transfusion medicine and hemotherapy promote the international exchange of knowledge within these disciplines. Consistent with this goal, continuing clinical education is also specifically addressed.
期刊最新文献
Erratum. Autoimmune Hemolytic Anemias: Challenges in Diagnosis and Therapy. Classical Haematology: Dynamic Development at the Interface of Transfusion Medicine and Haematology. Paroxysmal Nocturnal Hemoglobinuria, Pathophysiology, Diagnostics, and Treatment. Sickle Cell Disease.
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