Abstract：
OBJECTIVE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients.
METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients.
RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated.
CONCLUSIONS: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.
METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients.
RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated.
CONCLUSIONS: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.
摘要：
目的：抗粒细胞-巨噬细胞集落刺激因子自身抗体（抗GM-CSFAb）与加替隐球菌的发病机理有关（C.gattii）感染和肺泡蛋白沉积症（PAP）。它们的存在也被注意到在诺卡症病例中，尤其是那些患有疾病的人。这项研究描述了一系列病例，这些病例描述了抗GM-CSFAb在诺卡心症患者中的临床特征和特异性。
方法：在本研究中，招募了8例患者以确定是否存在抗GM-CSFAb.除了临床过程的详细描述，我们彻底调查了自身抗体的特征，同种型,子类，滴度,和中和能力通过利用来自患者的血浆样品。
结果：在8名患者中，五个抗GM-CSF抗体检测呈阳性，所有患者均有中枢神经系统（CNS）受累；这些抗体阴性的患者均未发生CNS诺卡心病。与以前记录的案件不同，我们的抗GM-CSFAb患者均未出现PAP症状。在我们的队列中，抗GM-CSFAb的滴度和中和活性与在隐球菌和PAP患者中发现的那些没有显着偏离。独特的,一个个体（患者3）显示抗GM-CSFAb的最小滴度和中和作用，与疾病严重程度无关。此外，IgM自身抗体在所研究的所有CNS诺卡尼病病例中均显着存在。
结论：抗GM-CSFAbs的存在提示个体有固有的免疫缺陷倾向于中枢神经系统诺卡心病。抗GM-CSFAb的存在有助于阐明中枢神经系统诺卡心病的脆弱性，即使自身抗体滴度低。因此,系统筛查抗GM-CSFAb应被视为诺卡心症患者的关键诊断步骤.
方法：在本研究中，招募了8例患者以确定是否存在抗GM-CSFAb.除了临床过程的详细描述，我们彻底调查了自身抗体的特征，同种型,子类，滴度,和中和能力通过利用来自患者的血浆样品。
结果：在8名患者中，五个抗GM-CSF抗体检测呈阳性，所有患者均有中枢神经系统（CNS）受累；这些抗体阴性的患者均未发生CNS诺卡心病。与以前记录的案件不同，我们的抗GM-CSFAb患者均未出现PAP症状。在我们的队列中，抗GM-CSFAb的滴度和中和活性与在隐球菌和PAP患者中发现的那些没有显着偏离。独特的,一个个体（患者3）显示抗GM-CSFAb的最小滴度和中和作用，与疾病严重程度无关。此外，IgM自身抗体在所研究的所有CNS诺卡尼病病例中均显着存在。
结论：抗GM-CSFAbs的存在提示个体有固有的免疫缺陷倾向于中枢神经系统诺卡心病。抗GM-CSFAb的存在有助于阐明中枢神经系统诺卡心病的脆弱性，即使自身抗体滴度低。因此,系统筛查抗GM-CSFAb应被视为诺卡心症患者的关键诊断步骤.
