自身免疫性肺泡蛋白沉积症患者临床影像学特征与生物学标志的关系

Relationship of Biomarkers with Clinical and Radiographic Characteristics in Autoimmune Pulmonary Alveolar Proteinosis

目的探讨自身免疫性肺泡蛋白沉积症（PAP）患者的临床特征及影像学与血清粒-巨细胞集落刺激因子自身抗体（GMAb）和血清细胞角蛋白碎片（CYFRA21-1）等生物学标志的关系。方法连续选取南京大学医学院附属鼓楼医院2006年1月至2012年12月血清GMAb阳性的PAP患者，收集患者临床影像学及CYFRA21—1等生物学标志资料，进行分析比较。结果共纳入26例肺泡蛋白沉积症患者，血清GMAb水平为28．64（19．2—75．4）μg／mL，均超过诊断界值2．39μg／mL，诊断为自身免疫性PAP。30例正常对照组的血清GMAb水平为0．10（0．05～0．15）Ixg／mL，均低于诊断界值。26例自身免疫性PAP中34．6％有职业吸入暴露史，血清GMAb水平与患者的疾病严重评分（DSS）、肺功能指标、高分辨率CT（HRCT）评分及血气分析等参数无显著相关性（P〉0．05），患者DSS与Pa02、FVC％pred、TLCO％pred及HRCT评分中的病灶范围评分（OE）和病灶严重度评分（OS）具有显著相关性（P〈0．05），患者的血清细胞角蛋白碎片（CYFRA21-1）水平为9．9（4．3—19．5）ng／mL，较正常对照组明显升高（P〈0．05），但升高水平与DSS、肺功能、影像学各指标无显著相关性（P〉0．05）。患者胸部HRCT表现为铺路石征比例为92．3％，表现为病灶地图样分布比例为100％。结论血清GMAb及血清CYFRA21—1可作为自身免疫性PAP患者的重要血清学诊断性标记，职业吸入暴露在自身免疫性PAP中较为常见。opacitysevefityscoreofchestHRCT（P〈0．05）．

Objective To describe the clinical,radiographic,and laboratory features of autoimmune pulmonary alveolar proteinosis （PAP） from a single center. Methods Consecutive autoimmune PAP cases diagnosed in the Nanjing Drum Tower Hospital between January 2006 and December 2012 were recruited in the study. The clinical, radiographic and laboratory data of the PAP patients were analyzed to explore the clinical significance of serum GM-CSF autoantibody （GMAb） and serum cytokeratin （CYFRA21-1）. Results The median serum GMAb level of the 26 cases was 28.64 μg/mL （ interquartile range, 19.2- 75.4 μg/mL） ,which were diagnosed as autoimmune PAP based on the serum GMAb levels of these patients all above the cut-off value of 2. 39 μg/mL while the serum GMAb levels of 30 normal controls were 0. 10 （0. 05-0. 15） μg/mL and all below the cut-off value. 34. 6% of all recruited 26 autoimmune PAP patients had identified occupational inhalational exposure. There was no significant correlation in the serum GMAb in autoimmune PAP patients with disease severity scores （DSS） ,lung function parameters, chest high resolution computed tomography （ HRCT ） scores, or PaO2 （ P 〉 0.05 ）. There was significant correlation of DSS of autoimmune PAP patients with PaO2, FVC% pred, TLCO% pred, opacity extent score of chest HRCT, and opacity severity score of chest HRCT （P 〈 0. 05 ）. The median serum level of CYFRA21-1 of the autoimmune PAP patients was 9.9 （4. 3-19. 5） ng/mL, which was significant higher than that of the normal control group （P 〈 0. 05）. However there was no significant correlation in the serum CYFRA21-1 in the autoimmune PAP patients with DSS,lung function parameters, and chest HRCT scores. 92. 3% of the chest HRCT of 26 autoimmune PAP patients had crazy paving sign,while 100% of them had geographic sparing sign. Conclusions Serum GMAb and CYFRA21-1 may be important biomarkers for diagnosis of autoimmane PAP. The PAP with occupational inhalational exposure constitutes a high proportion of autoimmune PAP patients.