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粒细胞集落刺激因子治疗的严重先天性中性粒细胞减少症患者的蛋白质网络改变和口腔健康干预的有益效果。

Protein Network Alterations in G-CSF Treated Severe Congenital Neutropenia Patients and Beneficial Effects of Oral Health Intervention.

机构信息

Division of Oral Health and Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.

Functional Genomics Center Zurich, ETH Zurich and University of Zurich, Zurich, Switzerland.

出版信息

Proteomics Clin Appl. 2024 Nov;18(6):e202400064. doi: 10.1002/prca.202400064. Epub 2024 Aug 3.

Abstract

PURPOSE

Severe congenital neutropenia (SCN) is a raredisorder characterized by diminished neutrophil levels. Despite granulocytecolony-stimulating factor (G-CSF) treatment, SCN patients remain still prone tosevere infections, including periodontal disease-a significant oral healthrisk. This study investigates the host proteome and metaproteome in saliva andgingival crevicular fluid (GCF) of G-CSF-treated patients.

EXPERIMENTAL DESIGN

We used label-free quantitative proteomics on saliva and GCF samples from SCN patients before (n = 10, mean age: 10.7 ± 6.6 years) and after a 6-month oral hygiene intervention (n = 9,mean age: 11.6 ± 5.27 years), and from 12 healthy controls.

RESULTS

We quantified 894 proteins in saliva (648 human,246 bacterial) and 756 proteins in GCF (493 human, 263 bacterial). Predominant bacterial genera included Streptococcus, Veillonella, Selenomonas, Corynebacterium, Porphyromonas, and Prevotella. SCN patients showed reduced antimicrobial peptides (AMPs) and elevated complement proteins compared tohealthy controls. Oral hygiene intervention improved oral epithelial conditionsand reduced both AMPs and complement proteins.

CONCLUSIONS AND CLINICAL RELEVANCE

SCN patients have aunique proteomic profile with reduced AMPs and increased complement proteins, contributing to infection susceptibility. Oral hygiene intervention not onlyimproved oral health in SCN patients but also offers potential overall therapeuticbenefits.

摘要

目的

严重先天性中性粒细胞减少症(SCN)是一种罕见疾病,其特征是中性粒细胞水平降低。尽管使用了粒细胞集落刺激因子(G-CSF)治疗,但 SCN 患者仍然容易发生严重感染,包括牙周病——这是一个重大的口腔健康风险。本研究调查了 G-CSF 治疗患者唾液和龈沟液(GCF)中的宿主蛋白质组和代谢蛋白质组。

实验设计

我们使用无标记定量蛋白质组学方法分析了 SCN 患者在接受 6 个月口腔卫生干预(n=9,平均年龄:11.6±5.27 岁)前后的唾液(n=10,平均年龄:10.7±6.6 岁)和 GCF 样本,以及 12 名健康对照者的样本。

结果

我们在唾液中定量了 894 种蛋白质(648 种人类蛋白质,246 种细菌蛋白质),在 GCF 中定量了 756 种蛋白质(493 种人类蛋白质,263 种细菌蛋白质)。主要的细菌属包括链球菌、韦荣球菌、唾液杆菌、棒状杆菌、卟啉单胞菌和普雷沃氏菌。与健康对照组相比,SCN 患者表现出抗菌肽(AMPs)减少和补体蛋白升高。口腔卫生干预改善了口腔上皮状况,同时降低了 AMPs 和补体蛋白。

结论和临床相关性

SCN 患者具有独特的蛋白质组学特征,表现为 AMPs 减少和补体蛋白增加,这导致了感染易感性。口腔卫生干预不仅改善了 SCN 患者的口腔健康,而且还提供了潜在的整体治疗益处。

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