THE SEVERE AND MODERATE PHENOTYPES OF HERITABLE MAC-1, LFA-1 DEFICIENCY - THEIR QUANTITATIVE DEFINITION AND RELATION TO LEUKOCYTE DYSFUNCTION AND CLINICAL-FEATURES
THE SEVERE AND MODERATE PHENOTYPES OF HERITABLE MAC-1, LFA-1 DEFICIENCY - THEIR QUANTITATIVE DEFINITION AND RELATION TO LEUKOCYTE DYSFUNCTION AND CLINICAL-FEATURES
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DOI：
10.1093/infdis/152.4.668
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发表时间：
1985-01-01
影响因子：
6.4
通讯作者：
SPRINGER, TA
中科院分区：
文献类型：
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作者：
ANDERSON, DC;SCHMALSTEIG, FC;SPRINGER, TA
在4名男性和4名女性患者中发现一种遗传性综合征，其特征为复发性或进行性坏死性软组织感染、脓液形成减少、伤口愈合受损、粒细胞增多和/或脐带脱落延迟。如免疫荧光流式细胞术中亚单位特异性单克隆抗体以及¹²⁵I免疫沉淀技术所示，除了NaB³H₄ - 半乳糖氧化酶标记测定外，这些个体的粒细胞、单核细胞或淋巴细胞存在Mac - 1、LFA - 1或p150,95（或其组合）的“中度”或“重度”缺陷——这三种结构相关的“黏附性”表面糖蛋白。根据所表达抗原的量确定了两种不同的表型。3名重度缺陷患者和4名中度缺陷患者在粒细胞表面分别表达这些分子的量为正常量的<0.3%和2.5% - 31%。这些患者临床感染并发症的严重程度与糖蛋白缺陷程度直接相关。与中度缺陷患者相比，重度缺陷患者在组织白细胞动员、粒细胞定向迁移、过度黏附、iC3b调理颗粒的吞噬作用以及补体或抗体依赖性细胞毒性方面存在更严重的异常。据推测，白细胞动员的体内异常反映了Mac - 1糖蛋白在内皮边缘化和组织渗出所需的黏附事件中的关键作用。认识到Mac - 1、LFA - 1缺陷患者的表型差异对于治疗策略可能很重要。
An inherited syndrome characterized by recurrent or progressive necrotic soft-tissue infections, diminished pus formation, impaired wound healing, granulocytosis, and/or delayed umbilical cord severance was recognized in four male and four female patients. As shown with subunit-specific monoclonal antibodies in immunofluorescence flow cytometry and 125I immunoprecipitation techniques, in addition to a NaB3H4-galactose oxidase labeling assay, granulocytes, monocytes, or lymphocytes from these individuals had a "moderate" or "severe" deficiency of Mac-1, LFA-1, or p150,95 (or a combination)-three structurally related "adhesive" surface glycoproteins. Two distinct phenotypes were defined on the basis of the quantity of antigen expressed. Three patients with severe deficiency and four patients with moderate deficiency expressed < 0.3% and 2.5%-31% of normal amounts of these molecules on granulocyte surfaces, respectively. The severity of clinical infectious complications among these patients was directly related to the degree of glycoprotein deficiency. More profound abnormalities of tissue leukocyte mobilization, granulocyte-directed migration, hyperadherence, phagocytosis of iC3b-opsonized particles, and complement- or antibody-dependent cytotoxicity were found in individuals with severe, as compared with moderate, deficiency. It is proposed that in vivo abnormalities of leukocyte mobilization reflect the critical roles of Mac-1 glycoproteins in adhesive events required for endothelial margination and tissue exudation. The recognition of phenotypic variation among patients with Mac-1, LFA-1 deficiency may be important with respect to therapeutic strategies.