Roles of the autoantibody against GM-CSF in the pathogenesis, diagnosis, and treatment for idiopathic pulmonary alveolar proteinosis

肺泡蛋白沉积症（PAP）是一种罕见的临床综合征，目前有三种公认的形式；先天性、继发性和后天性。超过90%的病例属于后一种类型，最近被定性为获得性自身免疫性疾病。在PAP中，表面活性剂的过量积累导致胸片上特征性的双侧空域混浊，计算机断层扫描上显示广泛的肺泡密度和小叶间隔增厚。PAP通常出现在先前健康的个体中，他们表现为几个月的呼吸困难和不同程度的肺气体转移受损。支气管肺泡灌洗液显示“乳状”，富含脂质的液体是特征性的，而肺活检显示轻度炎症肺泡均匀充满无定形嗜酸性物质，在电子显微镜下含有特征性的片层状体。目前关于获得性PAP发病机制的概念是，由于内源性细胞因子粒细胞-巨噬细胞集落刺激因子（GM-CSF）的营养生理信号被特异性多克隆自身抗体抑制，肺泡巨噬细胞清除功能受损，导致表面活性剂过量。目前的治疗包括全身麻醉下的全肺灌洗，根据临床情况需要反复进行，而一些成年患者也对重组人GM-CSF的反复给药有反应。

Pulmonary alveolar proteinosis (PAP) is a rare clinical syndrome with currently three recognised forms ; congenital, secondary and acquired. More than 90% of cases are of the latter type, which recently has been characterized as an acquired autoimmune disorder. In PAP excess accumulation of surfactant leads to characteristic bilateral airspace opacities on chest radiograph and extensive alveolar densities with thickened interlobular septa on computed tomography scan. PAP typically appears in previously healthy individuals, who present with several months of dyspnoea and impaired pulmonary gas transfer of variable severity. "Milky" appearing, lipid-rich fluid recovered at bronchoalveolar lavage is characteristic, while lung biopsy, when performed, shows minimally inflamed alveoli uniformly filled with amorphous eosinophilic material that on electron microscopy contains characteristic lamellar bodies. Current concepts of pathogenesis in acquired PAP are that the excess surfactant results from impaired clearance by alveolar macrophages, as a result of inhibition by specific polyclonal autoantibodies of trophic physiological signals from the endogenous cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). Current therapy consists of whole-lung lavage under general anesthesia, repeated as needed by clinical status, while some adult patients also respond to the repeated administration of recombinant human GM-CSF.