Dimanche-Boitrel M T, Guyot A, De Saint-Basile G, Fischer A, Griscelli C, Lisowska-Grospierre B
INSERM U132, Hôpital des Enfants-Malades, Paris, France.
Eur J Immunol. 1988 Oct;18(10):1575-9. doi: 10.1002/eji.1830181016.
Leukocyte adhesion deficiency (LAD) is a recessive autosomal disease characterized by life-threatening recurrent bacterial infections, by defective functions of leukocytes and by deficient membrane expression of leukocyte adhesion glycoproteins. These proteins, LFA-1, Mac-1 and p150,95, are alpha 1/beta 1 heterodimers composed of different alpha chains and of a common beta chain. Patients with the severe phenotype of the disease completely lack the three glycoproteins on cell surface. Previous studies showed a conserved synthesis of the LFA-1 alpha chain precursor in cytosol of patients' cells and an inconstant presence of the beta chain precursor. When present, precursors are in free form and not associated to alpha/beta complexes in the cells of patients with the severe phenotype. The availability of the beta chain cDNA probe allowed us to examine the beta chain gene expression in the lymphoblastoid cell lines of 4 patients. On the basis of the results obtained both at protein and RNA levels we can distinguish 3 types of mutations characterized by (a) barely detectable beta subunit messenger RNA and undetectable beta precursor, (b) decreased level of beta subunit mRNA and undetectable beta precursor and (c) normal beta subunit mRNA level and detectable beta precursor of normal size.
白细胞黏附缺陷症（LAD）是一种常染色体隐性疾病，其特征为危及生命的复发性细菌感染、白细胞功能缺陷以及白细胞黏附糖蛋白的膜表达不足。这些蛋白，即淋巴细胞功能相关抗原-1（LFA-1）、巨噬细胞抗原-1（Mac-1）和p150,95，是由不同的α链和一条共同的β链组成的α1/β1异二聚体。患有该疾病严重表型的患者在细胞表面完全缺乏这三种糖蛋白。先前的研究表明，患者细胞胞质溶胶中LFA-1α链前体的合成是保守的，而β链前体的存在则不稳定。当存在时，前体以游离形式存在，在具有严重表型的患者细胞中不与α/β复合物结合。β链cDNA探针的可用性使我们能够检测4名患者淋巴母细胞系中的β链基因表达。根据在蛋白质和RNA水平获得的结果，我们可以区分出3种类型的突变，其特征分别为：（a）几乎检测不到β亚基信使RNA且未检测到β前体；（b）β亚基mRNA水平降低且未检测到β前体；（c）β亚基mRNA水平正常且可检测到正常大小的β前体。
