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人类念珠菌病中的组织侵袭性和非酸性pH值与白色念珠菌在“体内”表达新单克隆抗体1H4所识别的碳水化合物表位相关。

Tissue invasiveness and non-acidic pH in human candidiasis correlate with "in vivo" expression by Candida albicans of the carbohydrate epitope recognised by new monoclonal antibody 1H4.

作者信息

Monteagudo C, Viudes A, Lazzell A, Martinez J P, Lopez-Ribot J L

机构信息

Department of Pathology University of Valencia, 46010 - Valencia, Spain.

出版信息

J Clin Pathol. 2004 Jun;57(6):598-603. doi: 10.1136/jcp.2003.013177.

Abstract

BACKGROUND

The morphogenetic conversion between yeast and hyphal growth forms appears to be crucial in the pathogenesis of invasive candidiasis, and can be regulated by environmental signals such as extracellular pH.

AIMS

To characterise the epitope recognised by monoclonal antibody 1H4, and to evaluate the expression of its corresponding epitope in Candida albicans cells under different conditions of pH and temperature, and "in vivo", in tissue samples from patients with human candidiasis.

METHODS

Monoclonal antibody 1H4 was generated against the 58 kDa cell wall mannoprotein of C albicans (mp58), and was further characterised by immunoblot analysis, periodate treatment of the antigenic preparations, and agglutination experiments of C albicans strains 3153A, SC5314, and 412, cultured under different environmental conditions (growth media and pH). An immunohistochemical study was performed in 24 human tissue samples from patients with mucocutaneous and systemic candidiasis.

RESULTS

1H4 recognises a pH sensitive carbohydrate epitope on the surface of C albicans cells, and this epitope is not restricted to mp58, but is shared with other cell wall mannoproteins. Immunohistochemical findings indicated that expression of the 1H4 epitope on C albicans cells in tissue sections from human candidiasis correlates with tissue invasion and pH of the niche. 1H4 immunoreactivity was also found in candida remnants within macrophages.

CONCLUSIONS

The fact that 1H4 epitope expression selectively identifies invasive forms of C albicans, in addition to candida remnants within macrophages, supports its potential value in the diagnosis and management of human candidiasis.

摘要

背景

酵母与菌丝生长形式之间的形态发生转换似乎在侵袭性念珠菌病的发病机制中至关重要,并且可受细胞外pH等环境信号调控。

目的

鉴定单克隆抗体1H4识别的表位,并评估其相应表位在不同pH和温度条件下以及在人类念珠菌病患者组织样本“体内”白色念珠菌细胞中的表达。

方法

针对白色念珠菌58 kDa细胞壁甘露糖蛋白(mp58)产生单克隆抗体1H4,并通过免疫印迹分析、抗原制剂的高碘酸盐处理以及在不同环境条件(生长培养基和pH)下培养的白色念珠菌菌株3153A、SC5314和412的凝集实验进一步进行鉴定。对24例皮肤黏膜和系统性念珠菌病患者的人体组织样本进行免疫组织化学研究。

结果

1H4识别白色念珠菌细胞表面的一个pH敏感碳水化合物表位,该表位不限于mp58,而是与其他细胞壁甘露糖蛋白共有。免疫组织化学结果表明,人类念珠菌病组织切片中白色念珠菌细胞上1H4表位的表达与组织侵袭和微环境的pH相关。在巨噬细胞内的念珠菌残余物中也发现了1H4免疫反应性。

结论

1H4表位表达除了能选择性识别巨噬细胞内的念珠菌残余物外,还能识别白色念珠菌的侵袭形式,这一事实支持了其在人类念珠菌病诊断和管理中的潜在价值。

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The C-terminal antibody binding domain of Candida albicans mp58 represents a protective epitope during candidiasis.
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本文引用的文献

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Fungal morphogenesis and host invasion.真菌形态发生与宿主侵袭。
Curr Opin Microbiol. 2002 Aug;5(4):366-71. doi: 10.1016/s1369-5274(02)00338-7.
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Virulence factors of Candida albicans.白色念珠菌的毒力因子
Trends Microbiol. 2001 Jul;9(7):327-35. doi: 10.1016/s0966-842x(01)02094-7.
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