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甘露糖结合凝集素在小儿血液肿瘤疾病感染并发症中的作用。

The Role of Mannose-binding Lectin in Infectious Complications of Pediatric Hemato-Oncologic Diseases.

机构信息

From the Department of Hematology, Heim Pál National Pediatric Institute, Budapest, Hungary.

Department of Internal Medicine, Research Laboratory, Semmelweis University, Budapest, Hungary.

出版信息

Pediatr Infect Dis J. 2021 Feb 1;40(2):154-158. doi: 10.1097/INF.0000000000002919.

Abstract

The complement system is essential for protection against infections in oncologic patients because of the chemotherapy-induced immunosuppression. One of the key elements in the activation of the complement system via the lectin pathway is the appropriate functioning of mannose-binding lectin (MBL) and mannose-binding lectin-associated serine protease 2 (MASP2) complex. The objective of our study was to find an association between polymorphisms resulting in low MBL level and activation of the MBL-MASP2 complex. Also, we aimed at finding a connection between these abnormalities and the frequency and severity of febrile neutropenic episodes in children suffering from hemato-oncologic diseases. Ninety-seven patients had been enrolled and followed from the beginning of the therapy for 8 months, and several characteristics of febrile neutropenic episodes were recorded. Genotypes of 4 MBL2 polymorphisms (-221C/G, R52C, G54D, G57E) were determined by real-time polymerase chain reaction. Activation of the MBL-MASP2 complex was evaluated by enzyme-linked immunosorbent assay at the time of diagnosis and during an infection. The number of febrile neutropenic episodes was lower, and the time until the first episode was longer in patients with normal MBL level than in patients with low MBL level coding genotypes. The MBL-MASP2 complex activation level correlated with the MBL genotype and decreased significantly during infections in patients with low MBL level. Our results suggest that infections after immunosuppression therapy in children suffering from hemato-oncologic diseases are associated with the MBL2 genotype. Our results may contribute to the estimation of risk for infections in the future, which may modify therapeutic options for individuals.

摘要

补体系统对于因化疗引起的免疫抑制而处于肿瘤患者的抗感染至关重要。凝集素途径中补体系统的激活的关键因素之一是甘露糖结合凝集素(MBL)和甘露糖结合凝集素相关丝氨酸蛋白酶 2(MASP2)复合物的正常功能。我们的研究目的是寻找导致 MBL 水平降低的多态性与 MBL-MASP2 复合物激活之间的关联。此外,我们旨在发现这些异常与患有血液肿瘤疾病的儿童发热性中性粒细胞减少症的发作频率和严重程度之间的联系。我们纳入了 97 名患者,并从治疗开始进行了 8 个月的随访,记录了发热性中性粒细胞减少症的几个特征。通过实时聚合酶链反应确定了 4 种 MBL2 多态性(-221C/G、R52C、G54D、G57E)的基因型。在诊断时和感染期间通过酶联免疫吸附试验评估 MBL-MASP2 复合物的激活。与低 MBL 水平编码基因型的患者相比,MBL 水平正常的患者的发热性中性粒细胞减少症发作次数更少,首次发作的时间更长。MBL-MASP2 复合物的激活水平与 MBL 基因型相关,并且在低 MBL 水平的患者感染期间显著降低。我们的结果表明,患有血液肿瘤疾病的儿童在免疫抑制治疗后的感染与 MBL2 基因型有关。我们的结果可能有助于未来对感染风险的评估,这可能会改变个体的治疗选择。

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