Abstract：
Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disorder involving production of autoantibodies against endogenous granulocyte-macrophage colony-stimulating factor (GM-CSF). This study aimed to identify biomarkers that could be used to monitor for aPAP, particularly in patients treated with anti-GM-CSF antibodies. This was an exploratory, prospective, observational, single-center study. Pre-specified biomarkers were evaluated between baseline and Day 120 in serum/plasma, whole blood, sputum and exhaled breath condensate from patients with aPAP, healthy volunteers, and patients with chronic obstructive pulmonary disease (COPD) and asthma (not treated with anti-GM-CSF and with no evidence of aPAP). Pulmonary function tests were also performed. Overall, 144 individuals were enrolled (aPAP: n = 34, healthy volunteers: n = 24, COPD: n = 40 and asthma: n = 46). Plasma GM-CSF levels were lower, and Krebs von den Lungen 6 and GM-CSF autoantibody ranges were higher, in patients with aPAP compared with other populations. Surfactant proteins-A and -D, lactate dehydrogenase and carcinoembryonic antigen ranges partially or completely overlapped across populations. Most plasma biomarkers showed high sensitivity and specificity for detection of aPAP; GM-CSF and GM-CSF autoantibody concentrations demonstrated equivalent sensitivity for differentiating aPAP. In addition to characteristic GM-CSF autoantibodies, assessment of plasma GM-CSF may identify individuals at risk of developing aPAP.Trial registration: EudraCT, 2012-003475-19. Registered 23 July 2012- https://eudract.ema.europa.eu/ .
摘要：
自身免疫性肺泡蛋白沉积症（aPAP）是一种罕见的肺部疾病，涉及产生针对内源性粒细胞-巨噬细胞集落刺激因子（GM-CSF）的自身抗体。这项研究旨在确定可用于监测aPAP的生物标志物，特别是在使用抗GM-CSF抗体治疗的患者中。这是一个探索性的,prospective,观察,单中心研究。在基线和第120天之间评估血清/血浆中预先指定的生物标志物，全血,aPAP患者的痰液和呼出气冷凝液，健康的志愿者,以及慢性阻塞性肺疾病（COPD）和哮喘患者（未使用抗GM-CSF治疗且无aPAP证据）。还进行了肺功能检查。总的来说,144名患者入组（aPAP：n=34，健康志愿者：n=24，COPD：n=40，哮喘：n=46）。血浆GM-CSF水平较低，KrebsvondenLungen6和GM-CSF自身抗体范围更高，与其他人群相比，aPAP患者。表面活性剂-A和-D,乳酸脱氢酶和癌胚抗原的范围在人群中部分或完全重叠.大多数血浆生物标志物显示出检测aPAP的高灵敏度和特异性;GM-CSF和GM-CSF自身抗体浓度显示出用于区分aPAP的同等灵敏度。除了特征性的GM-CSF自身抗体，血浆GM-CSF的评估可以确定有发生aPAP风险的个体。试用登记:EudraCT,2012-003475-19.2012年7月23日注册-https://eudract。EMA.欧罗巴。欧盟/。
