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抗粒细胞-巨噬细胞集落刺激因子自身抗体阳性隐球菌性脑膜炎患者的临床特征分析

Clinical characteristics of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor autoantibodies
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摘要 目的探讨抗粒细胞-巨噬细胞集落刺激因子(GM-CSF)自身抗体阳性隐球菌性脑膜炎患者的临床特征和预后影响因素。方法回顾性纳入2014年1月至2021年12月于复旦大学附属华山医院住院治疗且隐球菌培养阳性的非艾滋病相关隐球菌性脑膜炎确诊病例216例, 采用酶联免疫吸附测定法检测血清抗GM-CSF自身抗体水平, 比较抗体阳性和阴性隐球菌性脑膜炎患者的临床表现和预后。统计学比较主要采用χ2检验或Fisher确切概率法。采用Cox回归模型分析患者预后相关危险因素。结果 216例患者中, 抗GM-CSF自身抗体阳性者23例(10.6%)。23例患者中格特隐球菌感染者7例, 新型隐球菌感染者16例。抗GM-CSF自身抗体阳性组中格特隐球菌感染占30.4%(7/23), 高于抗体阴性组的1.6%(3/193), 差异有统计学意义(χ2=38.82, P<0.001)。抗GM-CSF自身抗体阳性组患者肺部有肿块型病灶(直径>3 cm)的比例为30.0%(6/20), 1年全因死亡率为50.0%(10/20), 分别高于抗体阴性组的3.4%(5/145)和16.1%(29/180), 差异均有统计学意义(均Fisher确切概率法, P<0.01)。年龄≥60岁[风险比(HR)=4.146, P=0.002]、合并免疫低下因素(HR=3.160, P=0.021)、癫痫(HR=6.129, P=0.002)、抗GM-CSF自身抗体阳性(HR=2.675, P=0.034)、脑脊液白细胞计数<100 ×106/L(HR=2.736, P=0.039)、脑脊液隐球菌荚膜多糖抗原效价≥1∶1 280(HR=4.361, P=0.009)是隐球菌性脑膜炎患者1年全因死亡的独立危险因素。结论在非艾滋病相关隐球菌性脑膜炎患者中, 抗GM-CSF自身抗体阳性率高达10.6%,抗体阳性患者可感染新型隐球菌和格特隐球菌, 其肺部出现肿块型病灶的比例显著多于抗体阴性患者。抗GM-CSF自身抗体阳性患者1年生存率下降, 为影响隐球菌性脑膜炎预后的独立危险因素。 Objective To investigate the clinical characteristics and prognosis of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor(GM-CSF)autoantibodies.Methods A total of 216 non-acquired immunodeficiency syndrome(AIDS)related cryptococcal meningitis cases with positive cultures of Cryptococcus,hospitalized at Huashan Hospital,Fudan University during January 2014 and December 2021,were retrospectively included.The serum anti-GM-CSF autoantibodies were detected by enzyme linked immunosorbent assay,and the clinical characteristics and prognosis were compared between patients with and without anti-GM-CSF autoantibodies.Statistical comparisons were mainly performed using the chi-square test or Fisher′s exact test.Cox proportional-hazards model was used to analyze the risk factors associated with prognosis.Results Among 216 enrolled patients,23 patients were positive of anti-GM-CSF autoantibodies,with a positive rate of 10.6%.Among 23 patients,seven cases were infected with Cryptococcus gattii,and 16 cases were infected with Cryptococcus neoformans.In the group with positive anti-GM-CSF autoantibodies,30.4%(7/23)of the patients were infected with Cryptococcus gattii,which was higher than that of 1.6%(3/193)in the group with negative anti-GM-CSF autoantibodies,and the difference was statistically significant(χ2=38.82,P<0.001).In the group with positive anti-GM-CSF autoantibodies,30.0%(6/20)had mass lesions with a diameter greater than three centimeters in the lungs,and the one-year all-cause mortality rate was 50.0%(10/20),which were both higher than those of 3.4%(5/145)and 16.1%(29/180)in the negative group,respectively.The differences were both statistically significant(both Fisher′s exact test,P<0.01).Age≥60 years(hazard ratio(HR)=4.146,P=0.002),predisposing factors(HR=3.160,P=0.021),epilepsy(HR=6.129,P=0.002),positive anti-GM-CSF autoantibodies(HR=2.675,P=0.034),white blood cell count of cerebrospinal fluid(CSF)<100×106/L(HR=2.736,P=0.039),the titers of cryptococcal capsular polysaccharide antigen of CSF≥1∶1280(HR=4.361,P=0.009)were independent risk factors for one-year all-cause mortality in patients with cryptococcal meningitis.Conclusions In non-AIDS related cryptococcal meningitis patients,the positive rate of serum anti-GM-CSF autoantibodies is as high as 10.6%.Patients with anti-GM-CSF autoantibodies could be infected with both Cryptococcus neoformans and Cryptococcus gattii,and they have higher proportion of lung mass lesions than patients with negative anti-GM-CSF autoantibodies.The one-year survival rate decreases significantly in patients with anti-GM-CSF autoantibodies,which is an independent risk factor for the prognosis of cryptococcal meningitis.
作者 罗钰 朱榕生 程家卉 周泠宏 邱文佳 黄钧天 江英骙 王璇 赵华真 朱利平 Luo Yu;Zhu Rongsheng;Cheng Jiahui;Zhou Linghong;Qiu Wenjia;Huang Juntian;Jiang Yingkui;Wang Xuan;Zhao Huazhen;Zhu Liping(Department of Infectious Diseases,Huashan Hospital,Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response,Shanghai Institute of Infectious Diseases and Biosecurity,National Medical Center for Infectious Diseases,Fudan University,Shanghai 200040,China)
出处 《中华传染病杂志》 CAS CSCD 2023年第8期495-501,共7页 Chinese Journal of Infectious Diseases
基金 国家重点研发计划(2021YFC2300400) 国家自然科学基金(81971911) 上海市市级科技重大专项(HS2021SHZX001)。
关键词 脑膜炎 隐球菌性 抗粒细胞-巨噬细胞集落刺激因子自身抗体 格特隐球菌 临床特征 预后 Meningitis,cryptococcal Anti-granulocyte-macrophage colony-stimulating factor autoantibody Cryptococcus gattii Clinical characteristics Prognosis
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