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糖基化研究在异基因造血干细胞移植后移植物抗宿主病中的潜力。

Potential of glycosylation research in graft versus host disease after allogeneic hematopoietic stem cell transplantation.

作者信息

Prenc Ema, Pulanic Drazen, Pucic-Bakovic Maja, Pezer Marija, Desnica Lana, Vrhovac Radovan, Nemet Damir, Pavletic Steven Z

机构信息

Croatian Cooperative Group for Hematologic Diseases, Zagreb, Croatia.

Division of Haematology, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia; University of Zagreb School of Medicine, Zagreb, Croatia; Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia.

出版信息

Biochim Biophys Acta. 2016 Aug;1860(8):1615-22. doi: 10.1016/j.bbagen.2016.02.015. Epub 2016 Feb 26.

Abstract

BACKGROUND

Glycans, complex oligosaccharides, are directly involved in almost every biological process, have a fundamental role in the immune system, and are probably involved in nearly every human disease. However, glycosylation has been greatly ignored in the area of allogeneic hematopoietic stem cell transplantation (alloHSCT) and graft versus host disease (GVHD). Both acute and chronic GVHD are multisystemic debilitating immunological disturbances arising after alloHSCT.

SCOPE OF REVIEW

In this paper, we review the glycosylation research already done in the field of alloHSCT and GVHD and evaluate further potential of glycan analysis in GVHD by looking into resembling inflammatory and autoimmune conditions.

MAJOR CONCLUSIONS

Glycan research could bring significant improvement in alloHSCT procedure with reduction in following complications, such as GVHD. Identifying glycan patterns that induce self-tolerance and the ones that cause the auto- and allo-immune response could lead to innovative and tissue-specific immunomodulative therapy instead of the current immunosuppressive treatment, enabling preservation of the graft-versus-tumor effect. Moreover, improved glycan pattern analyses could offer a more complete assessment and greatly needed dynamic biomarkers for GVHD.

GENERAL SIGNIFICANCE

This review is written with a goal to encourage glycan research in the field of alloHSCT and GVHD as a perspective tool leading to improved engraftment, discovery of much needed biomarkers for GVHD, enabling an appropriate therapy and improved monitoring of therapeutic response. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.

摘要

背景

聚糖,即复杂的寡糖,几乎直接参与了每一个生物过程,在免疫系统中发挥着重要作用,并且可能与几乎所有人类疾病都有关联。然而,在异基因造血干细胞移植(alloHSCT)和移植物抗宿主病(GVHD)领域,糖基化一直被极大地忽视。急性和慢性GVHD都是alloHSCT后出现的多系统衰弱性免疫紊乱。

综述范围

在本文中,我们回顾了在alloHSCT和GVHD领域已经开展的糖基化研究,并通过研究类似的炎症和自身免疫性疾病来评估聚糖分析在GVHD中的进一步潜力。

主要结论

聚糖研究可以显著改善alloHSCT程序,减少诸如GVHD等后续并发症。识别诱导自身耐受的聚糖模式以及引发自身免疫和同种异体免疫反应的聚糖模式,可能会带来创新的组织特异性免疫调节疗法,而非目前的免疫抑制治疗,从而保留移植物抗肿瘤效应。此外,改进的聚糖模式分析可以为GVHD提供更全面的评估和急需的动态生物标志物。

普遍意义

撰写本综述的目的是鼓励在alloHSCT和GVHD领域开展聚糖研究,将其作为一种有望改善植入、发现GVHD急需的生物标志物、实现适当治疗并改进治疗反应监测的工具。本文是名为“个性化医学中的聚糖”特刊的一部分,客座编辑:戈尔丹·劳克教授。

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Mechanisms of disease: The human N-glycome.疾病机制:人类N-糖组
Biochim Biophys Acta. 2016 Aug;1860(8):1574-82. doi: 10.1016/j.bbagen.2015.10.016. Epub 2015 Oct 21.
3
The Structural Role of Antibody N-Glycosylation in Receptor Interactions.抗体N-糖基化在受体相互作用中的结构作用
Structure. 2015 Sep 1;23(9):1573-1583. doi: 10.1016/j.str.2015.06.015. Epub 2015 Jul 23.

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