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Chronic Disseminated Candidiasis During Hematological Malignancies: An Immune Reconstitution Inflammatory Syndrome With Expansion of Pathogen-Specific T Helper Type 1 Cells.
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2020-05-11 , DOI: 10.1093/infdis/jiz688
Sophie Candon 1, 2 , Blandine Rammaert 3, 4, 5 , Anne Perrine Foray 1 , Baptiste Moreira 1 , Maria Pilar Gallego Hernanz 6 , Lucienne Chatenoud 1 , Olivier Lortholary 3, 7
Affiliation  

BACKGROUND Chronic disseminated candidiasis (CDC) is a rare disease that mostly occurs after chemotherapy-induced prolonged neutropenia in patients with hematological malignancies. It is believed to ensue from Candida colonization, breach of the intestinal epithelial barrier, and venous translocation to organs. Fungal blood or liver biopsy cultures are generally negative, suggesting the absence of an ongoing invasive fungal disease. METHODS To unravel the contribution of the immune system to CDC pathogenesis, we undertook a prospective multicentric exploratory study in 44 CDC patients at diagnosis and 44 matched controls. RESULTS Analysis of Candida-specific T-cell responses using enzyme-linked immunospot assays revealed higher numbers of interferon (IFN)γ-producing T cells reactive to mp65 or candidin in 27 CDC cases compared with 33 controls. Increased plasma levels of soluble CD25, interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and IL-10 and lower levels of IL-2 were observed in CDC patients versus controls. Neutrophilia and higher levels of CD4 and CD8 T-cell activation were found in CDC patients as well as increased proportions of CXCR3-expressing TCRγδ +Vδ2+ cells. CONCLUSIONS The expansion of Candida-specific IFNγ-producing T cells together with features of T-cell activation and systemic inflammation identified here support the view that CDC belongs to the broad spectrum of fungal-associated immune reconstitution inflammatory syndromes.

中文翻译:

血液系统恶性肿瘤中的慢性传播性念珠菌病:一种免疫重建炎症综合症,伴有病原体特异性T辅助1型细胞的扩增。

背景技术慢性传播性念珠菌病(CDC)是一种罕见疾病,多发生于化疗导致血液系统恶性肿瘤患者长期嗜中性白血球减少后。据信,这是由于念珠菌定植,破坏肠上皮屏障和静脉向器官移位而引起的。真菌血液或肝活检培养物通常为阴性,表明没有正在进行的侵袭性真菌病。方法为了揭示免疫系统对CDC发病机制的影响,我们对44例诊断为CDC的患者和44例相匹配的对照组进行了一项前瞻性多中心探索性研究。结果使用酶联免疫斑点法对念珠菌特异性T细胞反应的分析显示,与33例对照相比,在27例CDC病例中,产生对mp65或candidin有反应性的产生干扰素(IFN)γ的T细胞数量更高。在CDC患者中,与对照组相比,血浆可溶性CD25,白介素(IL)-6,IL-1β,肿瘤坏死因子-α和IL-10升高,IL-2降低。在CDC患者中发现中性粒细胞增多,CD4和CD8 T细胞活化水平升高,以及表达CXCR3的TCRγδ+Vδ2+细胞比例增加。结论此处确定的产生念珠菌特异性IFNγ的T细胞的扩增以及T细胞活化和全身性炎症的特征支持了CDC属于广泛的真菌相关免疫重建炎症综合征的观点。在CDC患者中发现中性粒细胞增多,CD4和CD8 T细胞活化水平升高,以及表达CXCR3的TCRγδ+Vδ2+细胞比例增加。结论此处确定的产生念珠菌特异性IFNγ的T细胞的扩增以及T细胞活化和全身性炎症的特征支持了CDC属于广泛的真菌相关免疫重建炎症综合症的观点。在CDC患者中发现中性粒细胞增多,CD4和CD8 T细胞活化水平升高,以及表达CXCR3的TCRγδ+Vδ2+细胞比例增加。结论此处确定的产生念珠菌特异性IFNγ的T细胞的扩增以及T细胞活化和全身性炎症的特征支持了CDC属于广泛的真菌相关免疫重建炎症综合征的观点。
更新日期:2019-12-27
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