目的:白细胞粘附缺陷(LAD)是一组罕见的以细菌感染为特征的遗传性先天性免疫错误(IEI),脐带残端延迟分离,和自身免疫。这项单中心研究旨在描述临床,免疫学,34名LAD-I埃及儿科患者的分子特征。
方法:34名患者的个人病史,记录了临床和实验室检查结果;研究了28例患者的遗传物质。通过Sanger测序进行突变分析。
结果:囊炎,皮肤和软组织感染,溃疡愈合不良,脐带残端延迟掉落,复发性或未解决的肺炎是最常见的表现,其次是慢性中耳炎,肠病,牙周炎;复发性口腔鹅口疮。所有患者均报告了持续的白细胞增多和中性粒细胞增多,以及CD18和CD11b缺乏。在约90%的患者中CD18表达<2%。在28例接受ITGβ2基因测序的患者中检测到16种不同的病理基因变异,其中,十个是小说,六个是以前报道的。三个家庭接受了产前诊断。患者根据培养结果服用抗菌药物,和预防性甲氧苄啶-磺胺甲恶唑5mg/kg,每天一次,定期临床随访。为4例患者提供造血干细胞移植(HSCT)。然而,由于疾病的严重程度和诊断的延误,58%的患者在生命的前2年内去世。
结论:本研究强调了在埃及儿童中早期诊断和分布ITGβ2基因突变的重要性。进一步的分子研究,然而,在该地区更好的疾病表征仍然是一个具有挑战性的必要性。
OBJECTIVE: Leukocyte adhesion deficiency (LAD) represents a rare group of inherited inborn errors of immunity (IEI) characterized by bacterial infections, delayed umbilical stump separation, and autoimmunity. This single-center study aimed at describing the clinical, immunological, and molecular characterizations of 34 LAD-I Egyptian pediatric patients.
METHODS: Details of 34 patients\' personal medical history, clinical and laboratory findings were recorded; Genetic material from 28 patients was studied. Mutational analysis was done by Sanger sequencing.
RESULTS: Omphalitis, skin and soft tissue infections with poorly healing ulcers, delayed falling of the umbilical stump, and recurrent or un-resolving pneumonia were the most common presentations, followed by chronic otitis media, enteropathy, periodontitis; and recurrent oral thrush. Persistent leukocytosis and neutrophilia were reported in all patients, as well as CD18 and CD11b deficiency. CD18 expression was < 2% in around 90% of patients. Sixteen different pathological gene variants were detected in 28 patients who underwent ITGß2 gene sequencing, of those, ten were novel and six were previously reported. Three families received a prenatal diagnosis. Patients were on antimicrobials according to culture\'s results whenever available, and on prophylactic Trimethoprim-Sulfamethoxazole 5 mg/kg once daily, with regular clinical follow up. Hematopoietic stem cell transplantation (HSCT) was offered for 4 patients. However due to severity of the disease and delay in diagnosis, 58% of the patients passed away in the first 2 years of life.
CONCLUSIONS: This study highlights the importance of early diagnosis and distribution of ITGß2 gene mutation in Egyptian children. Further molecular studies, however, remain a challenging necessity for better disease characterization in the region.