白细胞粘附缺陷(LAD)是由白细胞(尤其是中性粒细胞)与血管壁粘附的缺陷引起的免疫缺陷。因此,LAD患者患有严重的细菌感染和伤口愈合受损,伴有嗜中性粒细胞增多症。在LAD-I,出生后直接表现为脐带延迟分离,在ITGB2中发现了突变,ITGB2是编码β2整合素的β亚基(CD18)的基因。在罕见的LAD-II病中,选择素配体的岩藻糖基化受到干扰,由SLC35C1中的突变引起,该基因编码高尔基体系统的GDP岩藻糖转运蛋白。LAD-II患者缺乏H和LewisLea和Leb血型抗原。最后,在LAD-III中,造血表达的β整合素的构象激活受到干扰,导致白细胞和血小板功能障碍。最后一种综合征是由FERMT3突变引起的,在所有血细胞中编码kindlin-3蛋白,参与β整合素构象的调节。本文包含我们认为与各种形式的LAD相关的突变的更新。
Leukocyte adhesion deficiency (LAD) is an immunodeficiency caused by defects in the adhesion of leukocytes (especially neutrophils) to the blood vessel wall. As a result, patients with LAD suffer from severe bacterial infections and impaired wound healing, accompanied by neutrophilia. In LAD-I, characterized directly after birth by delayed separation of the umbilical cord, mutations are found in ITGB2, the gene that encodes the β subunit (CD18) of the β2 integrins. In the rare LAD-II disease, the fucosylation of selectin ligands is disturbed, caused by mutations in SLC35C1, the gene that encodes a GDP-fucose transporter of the Golgi system. LAD-II patients lack the H and Lewis Lea and Leb blood group antigens. Finally, in LAD-III, the conformational activation of the hematopoietically expressed β integrins is disturbed, leading to leukocyte and platelet dysfunction. This last syndrome is caused by mutations in FERMT3, encoding the kindlin-3 protein in all blood cells, involved in the regulation of β integrin conformation. This article contains an update of the mutations that we consider to be relevant for the various forms of LAD.