Serological diagnosis of idiopathic pulmonary alveolar proteinosis

Serological diagnosis of idiopathic pulmonary alveolar proteinosis
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DOI:
10.1164/ajrccm.162.2.9910032
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发表时间:
2000-08-01
影响因子:
24.7
通讯作者:
Nakata, K
Nakata, K
中科院分区:
医学1区
文献类型:
--
作者:
Kitamura, T;Uchida, K;Nakata, K

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在此之前,我们报告了11例日本特发性肺泡蛋白沉积症(I-PAP)患者支气管肺泡损伤液中抗粒细胞-巨噬细胞集落刺激因子(GM-CSF)的中和性自身抗体的特异性发生。在所有5例I-PAP患者的血清中也检测到自身抗体。为了确定自身抗体的存在并不局限于日本患者,我们检查了来自五个国家的24名I-PAP患者的血清,结果表明,这种自身抗体在这些患者中始终特异性存在。因此,检测血清中的自身抗体可用于诊断I-PAP。为了建立一种简便的诊断I-PAP的方法,我们建立了一种新的胶乳凝集试验,使用胶乳珠与重组人CM-CSF偶联。使用乳胶珠从血清中分离的GM-CSF结合蛋白被鉴定为IgG(1)和IgG(2)的自身抗体。通过该试验测定的自身抗体滴度与通过ELISA测定的自身抗体滴度相关。所有24例I-PAP患者的300倍稀释血清中凝集反应均为阳性,但4例继发性PAP患者、2例先天性PAP患者、40例其他肺部疾病患者和40例正常人中的38例血清中凝集反应为阴性。结果表明,乳胶凝集试验是一种可靠的诊断I-PAP的血清学方法,具有较高的敏感性(100%)和特异性(98%)。
Previously, we reported the specific occurrence of neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchoalveolar ravage fluid from 11 Japanese patients with idiopathic pulmonary alveolar proteinosis (I-PAP). The autoantibody was also detected in sera from all 5 I-PAP patients examined. To determine that the existence of the autoantibody is not limited to the Japanese patients, we examined sera from 24 I-PAP patients in five countries and showed that the autoantibody was consistently and specifically present in such patients. Thus, detection of the autoantibody in sera can be used for diagnosis of I-PAP. To establish a simple and convenient method for diagnosis of I-PAP, we developed a novel latex agglutination test using latex beads coupled with recombinant human CM-CSF. GM-CSF binding proteins isolated from the sera using the latex beads were identified as the autoantibodies of IgG(1) and IgG(2). The titer of the autoantibody determined by this test correlated with that determined by ELISA. Agglutination was positive in 300-fold diluted sera from all 24 I-PAP patients, but negative in sera from four secondary PAP patients, two congenital PAP patients, 40 patients with other lung diseases, and 38 of 40 normal subjects. These results establish that the latex agglutination test is a reliable method for serological diagnosis of I-PAP with high sensitivity (100%) and specificity (98%).