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，目前公认的三种类型：先天性、继发性和获得性。超过90%的病例是后一种类型，最近被描述为获得性自身免疫性疾病。在PAP中，表面活性物质的过度积聚导致胸部X线片上特征性的双侧空域混浊和CT扫描上广泛的肺泡密度和小叶间隔增厚。PAP通常出现在以前健康的人身上，他们有几个月的呼吸困难和不同严重程度的肺气体转运障碍。“乳白色”出现，在支气管肺泡灌洗中恢复的富脂液体是特征，而肺活检时，肺活检显示轻度炎症的肺泡均匀填充无定形嗜酸性物质，在电子显微镜下含有特征性的板层小体。目前关于获得性PAP发病机制的观点是，肺泡巨噬细胞对内源性细胞因子粒细胞-巨噬细胞集落刺激因子(GM-CSF)的营养生理信号的特异性多克隆自身抗体抑制，导致肺泡巨噬细胞清除功能受损。目前的治疗方法是在全身麻醉下进行全肺灌洗，根据临床情况重复使用，而一些成人患者也对重复使用重组人GM-CSF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.