Nakata Koh, Sugi Tatsuki, Kuroda Keiko, Yoshizawa Kazutaka, Takada Toshinori, Tazawa Ryushi, Ueda Takahiro, Aoki Ami, Abe Mitsuhiro, Tatsumi Koichiro, Eda Ryosuke, Kondoh Shotaro, Morimoto Konosuke, Tanaka Takeshi, Yamaguchi Etsuro, Takahashi Ayumu, Oda Miku, Ishii Haruyuki, Izumi Shinyu, Sugiyama Haruhito, Nakagawa Atsushi, Tomii Keisuke, Suzuki Masaru, Konno Satoshi, Ohkouchi Shinya, Hirano Taizou, Handa Tomohiro, Hirai Toyohiro, Inoue Yoshikazu, Arai Toru, Asakawa Katsuaki, Sakagami Takuro, Tanaka Takahiro, Mikami Ayako, Kitamura Nobutaka
Clinical and Translational Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan.
IVD Development Unit, Ina Laboratory, Medical and Biological Laboratories, Ltd, Nagoya, Japan.
ERJ Open Res. 2020 Jan 27;6(1). doi: 10.1183/23120541.00259-2019. eCollection 2020 Jan.
Very recently, a modest but significant efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation therapy for the treatment of mild to moderate autoimmune pulmonary alveolar proteinosis (aPAP) has been reported. As the ability to measure the level of GM-CSF autoantibody (GMAb) in the serum is required to decide the indication for this therapy, we developed a high-performance GMAb testing kit for clinical use. As the kit succeeded in reducing nonspecific IgG binding to the ELISA plate, the predictive performance shown in the training study to discriminate aPAP patients from healthy subjects was perfect, providing a cut-off value of 1.65 U·mL in 78 patients with aPAP and 90 healthy subjects in an operator-blinded manner using logistic regression analysis. As in the validation study, serum samples from another 213 patients with aPAP were also blinded and evaluated in an operator-blinded manner against external 207 samples from patients with other types of PAP and patients exhibiting various ground-glass opacities on chest high-resolution computed tomography that require discrimination from PAP. The logistic regression analysis of these validation data sets revealed values of 97.6% and 100% for specificity and sensitivity, respectively. Thus, this new GMAb testing kit is reliable for the diagnosis of aPAP and differential diagnosis of other lung diseases.
最近，有报道称粒细胞巨噬细胞集落刺激因子（GM-CSF）吸入疗法治疗轻度至中度自身免疫性肺泡蛋白沉积症（aPAP）具有一定疗效，虽不太显著，但意义重大。由于决定该疗法适应症需要测定血清中GM-CSF自身抗体（GMAb）水平的能力，我们开发了一种供临床使用的高性能GMAb检测试剂盒。该试剂盒成功减少了非特异性IgG与酶联免疫吸附测定（ELISA）板的结合，在训练研究中用于区分aPAP患者和健康受试者的预测性能极佳，通过逻辑回归分析，在78例aPAP患者和90名健康受试者中以操作者盲法得出的临界值为1.65 U·mL。在验证研究中，另外213例aPAP患者的血清样本也进行了盲法处理，并以操作者盲法与来自其他类型肺泡蛋白沉积症（PAP）患者以及胸部高分辨率计算机断层扫描显示各种磨玻璃影且需要与PAP进行鉴别的患者的207份外部样本进行评估。对这些验证数据集进行逻辑回归分析得出，特异性和敏感性值分别为97.6%和100%。因此，这种新型GMAb检测试剂盒对于aPAP的诊断以及其他肺部疾病的鉴别诊断是可靠的。
