Division of Allergy and Clinical Immunology, Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
J Allergy Clin Immunol. 2012 Jun;129(6):1588-93. doi: 10.1016/j.jaci.2012.02.003. Epub 2012 Mar 10.
Inherited defects in the function of adenosine deaminase (ADA) cause severe combined immunodeficiency (SCID) and affect many other cells and tissues.
We sought to characterize the frequency and features of pulmonary alveolar proteinosis (PAP) in patients with ADA deficiency.
Clinical and laboratory features of all patients with SCID caused by ADA deficiency in a single center were analyzed. Bronchoalveolar lavage (BAL) fluid and lung biopsy specimens were stained with hematoxylin and eosin and periodic acid-Schiff, visualized by means of electron microscopy, and studied for associated infections. As a control group, BAL fluid and biopsy specimens from 22 patients with SCID caused by other genetic abnormalities were similarly assessed.
Among 16 consecutive patients with ADA deficiency, 7 had BAL fluid containing periodic acid-Schiff-positive surfactant-like material with macrophages engulfing degenerating lamellar bodies and/or lung biopsy specimens with alveolar spaces filled with homogeneous granular eosinophilic material and large macrophages. The lung pathology was typical of PAP. Identification of various pathogens coincided with PAP in 3 of these patients. We have diagnosed PAP among patients with ADA deficiency more commonly in the last 10 years than previously (P= .05), likely reflecting increased awareness of this condition. There were no significant differences in the clinical or immunologic characteristics between patients with ADA deficiency with or without PAP. Similar findings of PAP were not found among patients with SCID caused by other genetic abnormalities (P= .001). ADA coupled to polyethylene glycol or allogeneic hematopoietic stem cell transplantation rapidly corrected this pulmonary complication. PAP seems to have contributed to the death of only 1 patient with ADA deficiency.
ADA deficiency predisposes to the development of PAP, which could be reversed after enzyme replacement or transplantation.
腺苷脱氨酶（ADA）功能遗传缺陷导致严重联合免疫缺陷（SCID），并影响许多其他细胞和组织。
我们旨在描述 ADA 缺乏症患者发生肺泡蛋白沉积症（PAP）的频率和特征。
分析单中心所有因 ADA 缺乏导致 SCID 的患者的临床和实验室特征。对支气管肺泡灌洗液（BAL）和肺活检标本进行苏木精和伊红及过碘酸希夫染色，电子显微镜下观察，并研究相关感染。作为对照组，同样评估了 22 例因其他遗传异常导致 SCID 的 BAL 液和活检标本。
在 16 例连续的 ADA 缺乏症患者中，7 例 BAL 液中含有过碘酸希夫阳性的表面活性剂样物质，巨噬细胞吞噬变性板层小体，或肺活检标本中肺泡腔充满均匀颗粒状嗜酸性物质和大巨噬细胞。肺部病理表现为典型的 PAP。在这 3 例患者中，发现了各种病原体的存在与 PAP 相一致。与以前相比，我们在过去 10 年中更常见地在 ADA 缺乏症患者中诊断 PAP（P=.05），这可能反映出对这种情况的认识提高。ADA 缺乏症患者中有无 PAP 的临床或免疫特征无显著差异。在因其他遗传异常导致 SCID 的患者中未发现 PAP 的类似发现（P=.001）。与 PEG 偶联的 ADA 或同种异体造血干细胞移植可迅速纠正这种肺部并发症。PAP 似乎仅导致 1 例 ADA 缺乏症患者死亡。
ADA 缺乏症易发生 PAP，经酶替代或移植后可逆转。
