Lessons from rare maladies: leukocyte adhesion deficiency syndromes.
Lessons from rare maladies: leukocyte adhesion deficiency syndromes.
复制标题
罕见疾病的教训：白细胞粘附缺乏综合征。
DOI：
10.1097/moh.0b013e32835a0091
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发表时间：
2013-01
影响因子：
3.2
通讯作者：
Zimmerman GA
中科院分区：
文献类型：
--
作者：
Harris ES;Weyrich AS;Zimmerman GA
白细胞粘附缺陷（LAD）综合征是罕见的遗传决定条件具有挑战性的临床特征。这些免疫缺陷也提供了与白细胞、血小板、细胞间相互作用和细胞内信号传导广泛相关的生物学见解。最近的发现值得在现有知识的背景下进行审查。最近发现了β2整合素的新活性，在ladi中缺乏或缺失，以及中性粒细胞和其他白细胞中新的β2整合素依赖功能。在LAD-II中，导致选择素配体聚焦受损以及选择素结合和信号传导缺陷的遗传缺陷和机制现在已经很明显。LAD-III除了白细胞粘附受损外，还表现出与Glanzmann血栓减少和血小板功能障碍相似的出血，现在已知是由于缺乏KINDLIN-3，一种与TALIN-1协同激活β1、β2和β3整合素的细胞质蛋白。了解白细胞粘附级联和白细胞与炎症内皮的相互作用，这是在每一个LAD综合征受损，继续完善。虽然LAD综合征是罕见的疾病，但它们的研究正在产生新的知识，直接适用于患者的诊断和护理，以及免疫生物学和止血的基本范式。
The leukocyte adhesion deficiency (LAD) syndromes are rare genetically determined conditions with challenging clinical features. These immunodeficiencies also provide insights that are broadly relevant to the biology of leukocytes, platelets, intercellular interactions, and intracellular signaling. Recent discoveries merit their review in the context of existing knowledge. New activities of β2 integrins, which are deficient or absent in LAD-I, and new β2 integrin-dependent functions of neutrophils and other leukocytes have recently been identified. Genetic defects and mechanisms accounting for impaired fucosylation of selectin ligands and defective selectin binding and signaling in LAD-II are now apparent. LAD-III, which presents with bleeding similar to that in Glanzmann thrombasthenia and platelet dysfunction in addition to impaired leukocyte adhesion, is now known to be due to absence of KINDLIN-3, a cytoplasmic protein that acts cooperatively with TALIN-1 in activating β1, β2, and β3 integrins. Understanding of the leukocyte adhesion cascade and interactions of leukocytes with inflamed endothelium, which are impaired in each of the LAD syndromes, continues to be refined. Although LAD syndromes are rare maladies, their investigation is generating new knowledge directly applicable to the diagnosis and care of patients and to fundamental paradigms in immunobiology and hemostasis.