Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Pediatr Pulmonol. 2021 Jul;56(7):2232-2241. doi: 10.1002/ppul.25373. Epub 2021 Mar 23.
The primary immunodeficiency syndromes of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency and lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency present with multisystem immune dysregulation. The aim of this study was to characterize and compare the pulmonary manifestations of these two diseases.
We retrospectively analyzed the pulmonary clinical, radiologic, and histopathologic characteristics of six patients with CTLA-4 haploinsufficiency and four patients with LRBA deficiency with pulmonary involvement followed at a large tertiary care center.
Chronic respiratory symptoms were more frequent in patients with LRBA deficiency versus CTLA-4 haploinsufficiency (3/4 vs. 1/6). Cough was the most common respiratory symptom. Abnormalities in pulmonary exam and pulmonary function testing were more frequent in LRBA deficiency (4/4, 2/4) compared to CTLA-4 haploinsufficiency (1/6, 2/6). Chest computed tomography (CT) findings included mediastinal lymphadenopathy (4/4 in LRBA deficiency vs. 1/4 in CTLA-4 haploinsufficiency), pulmonary nodules (4/4, 3/4), ground-glass opacification (4/4, 3/4), and bronchiectasis (3/4, 1/4). Lymphocytic inflammation, concentrated bronchovasculocentrically and paraseptally, was the predominant pathologic finding and was observed in all patients who had lung biopsies (N = 3 with LRBA deficiency; N = 3 with CTLA-4 haploinsufficiency).
Despite phenotypic overlap amongst these diseases, LRBA deficiency demonstrated greater severity of pulmonary disease, indicated by respiratory symptoms, pulmonary exam, and intrathoracic radiologic findings. Chest CT was the most sensitive indicator of pulmonary involvement in both disorders. Lymphocytic inflammation is the key histologic feature of both disorders. Pediatric pulmonologists should consider these disorders of immune dysregulation in the relevant clinical context to provide earlier diagnosis, comprehensive pulmonary evaluation and treatment.
细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）单倍体不足和脂多糖反应性 beige 样锚蛋白（LRBA）缺乏的原发性免疫缺陷综合征表现为多系统免疫失调。本研究旨在描述和比较这两种疾病的肺部表现。
我们回顾性分析了在一家大型三级保健中心就诊的 6 例 CTLA-4 单倍体不足和 4 例 LRBA 缺陷伴肺部受累患者的肺部临床、影像学和组织病理学特征。
LRBA 缺陷患者比 CTLA-4 单倍体不足患者更常出现慢性呼吸道症状（3/4 比 1/6）。咳嗽是最常见的呼吸道症状。LRBA 缺陷（4/4，2/4）比 CTLA-4 单倍体不足（1/6，2/6）更常出现肺部检查和肺功能测试异常。胸部计算机断层扫描（CT）结果包括纵隔淋巴结病（LRBA 缺陷 4/4，CTLA-4 单倍体不足 1/4）、肺结节（LRBA 缺陷 4/4，3/4）、磨玻璃影（LRBA 缺陷 4/4，3/4）和支气管扩张（LRBA 缺陷 3/4，1/4）。淋巴样炎症，集中在支气管血管中心和旁间隔，是主要的病理发现，所有进行肺活检的患者（LRBA 缺陷 3 例；CTLA-4 单倍体不足 3 例）均可见到。
尽管这些疾病存在表型重叠，但 LRBA 缺陷表现出更严重的肺部疾病，表现为呼吸道症状、肺部检查和胸内放射学发现。胸部 CT 是这两种疾病中最敏感的肺部受累指标。淋巴样炎症是两种疾病的关键组织学特征。儿科肺病专家应在相关临床背景下考虑这些免疫失调疾病，以提供更早的诊断、全面的肺部评估和治疗。
