Immunology Department, Armed Forces Institute of Pathology, Rawalpindi, Pakistan.
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Immunobiology. 2020 May;225(3):151938. doi: 10.1016/j.imbio.2020.151938. Epub 2020 Apr 2.
Leukocyte adhesion deficiency I (LADI) is an autosomal recessive type of primary immunodeficiency characterized by occurrence of repeated bacterial infections, impaired pus formation and wound healing. Genetic variations in the β-2 integrin subunit encoding gene ITGB2 have been implicated in causing the disorder. In the present study, we have investigated twelve patients presenting LAD1 features. After collecting clinical and family history, flow cytometry was used to determine levels of CD18 in the patients. Clinical history revealed that umbilical cord separation occurred mostly after 19 days in the patients. Recurrent skin infections were found in seven patients. Eight patients had at least one elder sibling who died due to repeated infections. All patients had marked neutrophilia with only 0.77% of neutrophils expressing CD18. Total 12 patients suffering from LAD1 were Sanger sequenced for ITGB2 gene. Five variants, including a novel p.(Cys286Phe) and four previously reported [p.(Gly273Arg), p.(Asp128Tyr), p.(Cys62*), IVS7 + 1G > A] were identified in 8 cases, while no pathogenic variant was observed in remaining four cases. This study represents the first comprehensive clinical and genetic characterization of LAD1 in Pakistani population. This will facilitate diagnosis and genetic counselling of patients with immunodeficiency disorders in Pakistani population.
白细胞黏附缺陷 I 症（LADI）是一种常染色体隐性遗传的原发性免疫缺陷病，其特征为反复发生细菌性感染、脓液形成和伤口愈合受损。编码β-2 整合素亚基的基因 ITGB2 的遗传变异与该疾病的发生有关。在本研究中，我们调查了 12 名表现出 LADI 特征的患者。在收集临床和家族病史后，使用流式细胞术来确定患者 CD18 的水平。临床病史显示，患者的脐带分离大多发生在 19 天后。7 名患者出现反复皮肤感染。8 名患者至少有一位因反复感染而死亡的年长兄弟姐妹。所有患者均有明显的中性粒细胞增多，仅有 0.77%的中性粒细胞表达 CD18。共有 12 名患有 LAD1 的患者接受了 ITGB2 基因的 Sanger 测序。在 8 例中发现了 5 种变异，包括一种新的 p.(Cys286Phe)和 4 种先前报道的 [p.(Gly273Arg)、p.(Asp128Tyr)、p.(Cys62*)、IVS7 + 1G > A]，而在其余 4 例中未观察到致病变异。本研究代表了对巴基斯坦人群中 LADI 的首次全面临床和遗传特征描述。这将有助于巴基斯坦人群中免疫缺陷疾病患者的诊断和遗传咨询。
