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方法学评价文献关于分析补体成分的遗传变异或蛋白水平对感染锥虫易感性的影响:系统综述。

Methodological Appraisal of Literature Concerning the Analysis of Genetic Variants or Protein Levels of Complement Components on Susceptibility to Infection by Trypanosomatids: A Systematic Review.

机构信息

Laboratório de Biologia Celular, Instituto Carlos Chagas, Fundação Oswaldo Cruz (FIOCRUZ), Curitiba, Brazil.

Laboratório de Biologia Básica de Células-Tronco, Instituto Carlos Chagas, Fundação Oswaldo Cruz (FIOCRUZ), Curitiba, Brazil.

出版信息

Front Immunol. 2021 Nov 25;12:780810. doi: 10.3389/fimmu.2021.780810. eCollection 2021.

Abstract

BACKGROUND

Trypanosomatids are protozoa responsible for a wide range of diseases, with emphasis on Chagas Disease (CD) and Leishmaniasis, which are in the list of most relevant Neglected Tropical Diseases (NTD) according to World Health Organization (WHO). During the infectious process, immune system is immediately activated, and parasites can invade nucleated cells through a broad diversity of receptors. The complement system - through classical, alternative and lectin pathways - plays a role in the first line of defense against these pathogens, acting in opsonization, phagocytosis and lysis of parasites. Genetic modifications in complement genes, such as Single Nucleotide Polymorphisms (SNPs), can influence host susceptibility to these parasites and modulate protein expression.

METHODS

In March and April 2021, a literature search was conducted at the PubMed and Google Scholar databases and the reference lists obtained were verified. After applying the inclusion and exclusion criteria, the selected studies were evaluated and scored according to eleven established criteria regarding their thematic approach and design, aiming at the good quality of publications.

RESULTS

Twelve papers were included in this systematic review: seven investigating CD and five focusing on Leishmaniasis. Most articles presented gene and protein approaches, careful determination of experimental groups, and adequate choice of experimental techniques, although several of them were not up-to-date. Ten studies explored the association of polymorphisms and haplotypes with disease progression, with emphasis on lectin complement pathway genes. Decreased and increased patient serum protein levels were associated with susceptibility to CD and Visceral Leishmaniasis, respectively.

CONCLUSION

This systematic review shows the influence of genetic alterations in complement genes on the progression of several infectious diseases, with a focus on conditions caused by trypanosomatids, and contributes suggestions and evidence to improve experimental design in future research proposals.

摘要

背景

动基体原虫是一类引起广泛疾病的原生动物,主要包括恰加斯病(CD)和利什曼病,它们被世界卫生组织(WHO)列为最重要的被忽视热带病(NTD)之一。在感染过程中,免疫系统会立即被激活,寄生虫可以通过广泛的受体侵入有核细胞。补体系统 - 通过经典、替代和凝集素途径 - 在抵御这些病原体的第一线中发挥作用,作用包括寄生虫的调理作用、吞噬作用和溶解作用。补体基因的遗传改变,如单核苷酸多态性(SNP),可以影响宿主对这些寄生虫的易感性,并调节蛋白表达。

方法

2021 年 3 月至 4 月,在 PubMed 和 Google Scholar 数据库中进行了文献检索,并对获得的参考文献进行了验证。在应用纳入和排除标准后,根据十一项既定标准评估和评分所选研究,旨在评估出版物的质量。

结果

本系统评价共纳入 12 篇论文:7 篇研究 CD,5 篇研究利什曼病。大多数文章都采用了基因和蛋白方法,仔细确定了实验组,并选择了合适的实验技术,尽管其中一些技术已经过时。有 10 项研究探讨了遗传多态性和单倍型与疾病进展的相关性,重点是凝集素补体途径基因。降低和增加患者血清蛋白水平分别与 CD 和内脏利什曼病的易感性相关。

结论

本系统评价表明,补体基因遗传改变对几种传染病的进展有影响,重点是动基体原虫引起的疾病,并为未来的研究建议提供了改进实验设计的建议和证据。

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