Adenosine deaminase deficiency and severe combined immunodeficiency disease.
Adenosine deaminase deficiency and severe combined immunodeficiency disease.
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腺苷脱氨酶缺乏症和严重联合免疫缺陷病。
DOI：
10.1002/9780470122969.ch4
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
Seegmiller,JE
中科院分区：
文献类型：
--
作者：
Thompson,LF;Seegmiller,JE
1972年，Eloise Giblett博士和她的同事（1）报道了一种遗传性腺苷脱氨酶（腺苷氨基水解酶，EC 3.5）缺乏症。4.4)两名患有严重联合免疫缺陷病（SCID）的无血缘关系的女性儿童的红细胞溶血产物。与许多重大的科学发现一样，围绕腺苷脱氨酶（ADA）缺乏症的描述的事件是偶然的。1972年，骨髓移植是治疗严重联合免疫缺陷症的唯一已知方式。Giblett博士在使用ADA同工酶作为遗传标记方面的专业知识被第一名患者的初级保健医生要求作为他们寻找合适的组织相容性骨髓供体的一部分。出乎意料的是，患者溶血产物的淀粉凝胶电泳显示未检测到ADA，尽管先前已检查了数千名其他个体的红细胞的ADA同工酶模式，未报告ADA缺乏症病例。第二个患有ADA缺乏症和SCID的孩子的发现促使Giblett和她的同事报告了他们的发现（1）。这是酶异常与特异性免疫疾病之间关联的第一个实例，也是维持正常免疫功能需要完整嘌呤分解代谢途径的第一个证据。酶缺乏和免疫系统缺陷（如SCID）之间的因果关系对大多数免疫学家来说是陌生的，这导致了另一种解释的建议，即DNA的小缺失包括HL-A基因座的免疫应答基因和。一个被认为与ADA相邻的结构基因（2）。然而，随着随后鉴定出20多名ADA缺乏症和SCID患者（3-5），其中一些患者在各种组织中具有低残留ADA活性（5），这一主张变得越来越不可能，并且随后将组织相容性基因座分配到6号染色体（6）和ADA基因座分配到20号染色体（7），这一主张完全站不住脚。完整的嘌呤补救途径对免疫系统正常发育的必要性的进一步证据来自Giblett博士随后报告的T细胞免疫缺陷儿童嘌呤核苷磷酸化酶缺乏症（8）。在这两种特异性免疫的遗传性疾病中发现结构改变的酶作为异常基因产物（9- 11）为生物化学家提供了线索
In 1972 Dr. Eloise Giblett and her colleagues (1) reported an inherited deficiency of the enzyme adenosine deaminase (adenosine aminohydrolase, EC 3.5. 4.4) in red blood cell hemolysates of two unrelated female children with severe combined immunodeficiency disease (SCID). As with many significant scientific discoveries, events surrounding the description of adenosine deaminase (ADA) deficiency were serendipitous. In 1972 bone marrow transplantation was the only known mode of therapy for severe combined immunodeficiency. Dr. Giblett’s expertise in the use of isozymes of ADA as genetic markers was requested by the primary care physicians of the first patient as part of their search for a suitable histocompatible bone marrow donor. Unexpectedly, starch gel electrophoresis of the patient’s hemolysate showed no detectable ADA, even though the red cells of thousands of other individuals had been previously examined for ADA isozyme patterns with no reported cases of ADA deficiency. The discovery of a second child with ADA deficiency and SCID prompted Giblett and her colleagues to report their findings (1). This was the first instance of an association between an enzyme abnormality and a disease of specific immunity and represented the first evidence for the necessity of an intact purine catabolic pathway for maintenance of normal immune function. A causal relationship between an enzyme deficiency and a defect in the immune system such as SCID was foreign to the thinking of most immunologists, which led to a proposal of an alternative explanation in which a small deletion of DNA included both the immune response genes of the HL-A locus and. a supposedly adjacent structural gene for ADA (2). However, this proposition became increasingly unlikely with the subsequent identification of over two dozen additional individuals with ADA deficiency and SCID (3-5), some of whom had low residual ADA activity in a variety of tissues (5), and was completely untenable with the subsequent assignment of the histocompatibility locus to chromosome No. 6 (6) and the ADA locus to chromosome No. 20 (7). Further evidence for the necessity of an intact purine salvage pathway for the normal development of the immune system came from Dr. Giblett’s subsequent report of a deficiency of purine nucleoside phosphorylase in a child with T-cell immunodeficiency (8). The discovery of structurally altered enzymes as the abnormal gene products in both these inherited diseases of specific immunity (9-1 1) provided biochemists with clues