van de Sande Wendy W J, Janse Dirk-Jan, Hira Vishal, Goedhart Heidy, van der Zee Ruurd, Ahmed Abdalla O A, Ott Alewijn, Verbrugh Henri, van Belkum Alex
Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Centre Rotterdam, Rotterdam, The Netherlands.
J Immunol. 2006 Aug 1;177(3):1997-2005. doi: 10.4049/jimmunol.177.3.1997.
About 40 years ago Abs against the fungus Madurella mycetomatis were first demonstrated to be present in eumycetoma patients, a disease characterized by tumorous swellings. To date nothing is known about the individual immunoreactive Ags present in this fungus. In the present study, we identify its first immunogenic Ag, a protein homologous to the translationally controlled tumor protein (TCTP), a well-conserved histamine release factor in a range of eukaryotes. The gene for this Ag was demonstrated to be present in two variants in M. mycetomatis, with 13% aa difference between the two proteins encoded. In vitro, TCTP was secreted into the culture medium. In vivo, it was found to be expressed on hyphae present in developing stages of the eumycetoma-characteristic black grain. Significant IgG and IgM immune responses, against the whole protein and selected M. mycetomatis-specific peptides, were determined. The Ab levels correlated with lesion size and disease duration. Overall, the patients with the largest lesions had the highest Ab level, which lowered with decreasing size of the lesion. After 6-15 years of disease duration the Ab levels were the highest. TCTP is the first well-characterized immunogenic Ag, simultaneously the first monomolecular vaccine candidate, identified for the fungus M. mycetomatis.
大约40年前,首次证明了在足菌肿患者体内存在抗真菌马杜拉足菌肿霉的抗体,足菌肿是一种以肿瘤样肿胀为特征的疾病。迄今为止,对于这种真菌中存在的个体免疫反应性抗原尚一无所知。在本研究中,我们鉴定了其首个免疫原性抗原,一种与翻译调控肿瘤蛋白(TCTP)同源的蛋白质,TCTP是一系列真核生物中一种高度保守的组胺释放因子。已证明该抗原的基因在马杜拉足菌肿霉中以两种变体形式存在,所编码的两种蛋白质之间氨基酸差异为13%。在体外,TCTP分泌到培养基中。在体内,发现它在足菌肿特征性黑色颗粒发育阶段的菌丝上表达。测定了针对全蛋白和选定的马杜拉足菌肿霉特异性肽段的显著IgG和IgM免疫反应。抗体水平与病变大小和疾病持续时间相关。总体而言,病变最大的患者抗体水平最高,随着病变大小减小而降低。疾病持续6至15年后,抗体水平最高。TCTP是首个得到充分表征的免疫原性抗原,同时也是首个为马杜拉足菌肿霉鉴定出的单分子疫苗候选物。