Laboratory of Human Immunology and Infectious Diseases, Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
J Clin Immunol. 2022 Nov;42(8):1730-1741. doi: 10.1007/s10875-022-01341-2. Epub 2022 Aug 10.
Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are a predisposing factor for pulmonary alveolar proteinosis (PAP) and Cryptococcus gattii cryptococcosis. This study aimed to investigate clinical manifestations in anti-GM-CSF Ab-positive patients with C. gattii cryptococcosis and analyze the properties of anti-GM-CSF Abs derived from these patients and patients with PAP.
Thirty-nine patients diagnosed with cryptococcosis (caused by C. neoformans or C. gattii) and 6 with PAP were enrolled in the present study. Clinical information was obtained from medical records. Blood samples were collected for analysis of autoantibody properties. We also explored the National Health Insurance Research Database (NHIRD) of Taiwan to investigate the epidemiology of cryptococcosis and PAP.
High titers of neutralizing anti-GM-CSF Abs were identified in 15 patients with cryptococcosis (15/39, 38.5%). Most anti-GM-CSF Ab-positive cryptococcosis cases had central nervous system (CNS) involvement (14/15, 93.3%). Eleven out of 14 (78.6%) anti-GM-CSF Ab-positive CNS cryptococcosis patients were confirmed to be infected with C. gattii, and PAP did not occur synchronously or metachronously in a single patient from our cohort. Exploration of an association between HLA and anti-GM-CSF Ab positivity or differential properties of autoantibodies from cryptococcosis patients and PAP yielded no significant results.
Anti-GM-CSF Abs can cause two diseases, C. gattii cryptococcosis and PAP, which seldom occur in the same subject. Current biological evidence regarding the properties of anti-GM-CSF Abs cannot provide clues regarding decisive mechanisms. Further analysis, including more extensive cohort studies and investigations into detailed properties, is mandatory to better understand the pathogenesis of anti-GM-CSF Abs.
抗粒细胞-巨噬细胞集落刺激因子自身抗体（anti-GM-CSF Abs）是肺泡蛋白沉积症（PAP）和新型隐球菌隐球菌病的易感因素。本研究旨在探讨抗 GM-CSF Ab 阳性新型隐球菌隐球菌病患者的临床表现，并分析这些患者和 PAP 患者来源的抗 GM-CSF Abs 的特性。
本研究纳入了 39 例诊断为隐球菌病（由新型隐球菌或新型隐球菌引起）和 6 例 PAP 的患者。从病历中获取临床信息。采集血样分析自身抗体特性。我们还探索了台湾全民健康保险研究数据库（NHIRD），以调查隐球菌病和 PAP 的流行病学。
在 39 例隐球菌病患者中（15/39，38.5%）发现了高滴度的中和抗 GM-CSF Abs。大多数抗 GM-CSF Ab 阳性隐球菌病患者有中枢神经系统（CNS）受累（14/15，93.3%）。14 例抗 GM-CSF Ab 阳性 CNS 隐球菌病患者中有 11 例（78.6%）被确认为感染了新型隐球菌，且在我们的队列中，单一患者并未同时或先后发生 PAP。对 HLA 与抗 GM-CSF Ab 阳性或隐球菌病患者和 PAP 患者来源的自身抗体的差异特性之间的相关性进行探索，未得出显著结果。
抗 GM-CSF Abs 可引起两种疾病，新型隐球菌隐球菌病和 PAP，这两种疾病很少在同一患者中同时发生。目前关于抗 GM-CSF Abs 特性的生物学证据不能提供关于决定性机制的线索。需要进一步分析，包括更广泛的队列研究和对详细特性的调查，以更好地了解抗 GM-CSF Abs 的发病机制。
