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利用流式细胞术评估一种新型药物对多发性硬化症的疗效。

The use of flow cytometry to assess a novel drug efficacy in multiple sclerosis.

作者信息

Benedek Gil, Meza-Romero Roberto, Bourdette Dennis, Vandenbark Arthur A

机构信息

Neuroimmunology Research, Department of Veterans Affairs Medical Center, Portland, OR, USA.

出版信息

Metab Brain Dis. 2015 Aug;30(4):877-84. doi: 10.1007/s11011-014-9634-0. Epub 2014 Dec 12.

Abstract

Applying different technologies to monitor disease activity and treatment efficacy are essential in a complex disease such as multiple sclerosis. Combining current assays with flow cytometry could create a powerful tool for such analyses. The cell surface expression level of CD74, the MHC class II invariant chain, is a potential disease biomarker that could be monitored by FACS analysis in order to assess disease progression and the clinical efficacy of partial MHC class II constructs in treating MS. These constructs, which can bind to and down-regulate CD74 cell-surface expression on monocytes and inhibit macrophage migration inhibitory factor (MIF) effects, can reverse clinical and histological signs of EAE. These properties of partial class II constructs are highly compatible with a flow cytometry approach for monitoring CD74 expression as a possible biomarker for disease activity/progression and as a treatment response marker.

摘要

在诸如多发性硬化症这样的复杂疾病中,应用不同技术监测疾病活动和治疗效果至关重要。将当前检测方法与流式细胞术相结合可为这类分析创造一个强大的工具。MHC II类恒定链CD74的细胞表面表达水平是一种潜在的疾病生物标志物,可通过荧光激活细胞分选分析进行监测,以评估疾病进展以及部分MHC II类构建体治疗多发性硬化症的临床疗效。这些构建体可结合并下调单核细胞上CD74的细胞表面表达,并抑制巨噬细胞迁移抑制因子(MIF)的作用,能够逆转实验性自身免疫性脑脊髓炎的临床和组织学症状。部分II类构建体的这些特性与用于监测CD74表达的流式细胞术方法高度兼容,CD74表达可作为疾病活动/进展的可能生物标志物以及治疗反应标志物。

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本文引用的文献

1
HLA-DRα1 constructs block CD74 expression and MIF effects in experimental autoimmune encephalomyelitis.
J Immunol. 2014 May 1;192(9):4164-73. doi: 10.4049/jimmunol.1303118. Epub 2014 Mar 28.
2
Immune cell subtyping in the cerebrospinal fluid of patients with neurological diseases.
J Neurol. 2014 Jan;261(1):130-43. doi: 10.1007/s00415-013-7145-2. Epub 2013 Oct 27.
3
A novel HLA-DRα1-MOG-35-55 construct treats experimental stroke.
Metab Brain Dis. 2014 Mar;29(1):37-45. doi: 10.1007/s11011-013-9440-0.
4
Partial MHC class II constructs inhibit MIF/CD74 binding and downstream effects.
Eur J Immunol. 2013 May;43(5):1309-21. doi: 10.1002/eji.201243162. Epub 2013 Apr 10.
9
Macrophage migration inhibitory factor and CD74 regulate macrophage chemotactic responses via MAPK and Rho GTPase.
J Immunol. 2011 Apr 15;186(8):4915-24. doi: 10.4049/jimmunol.1003713. Epub 2011 Mar 16.
10
Stoichiometry of HLA class II-invariant chain oligomers.
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