Translationally Controlled Tumor Protein from Madurella mycetomatis, a Marker for Tumorous Mycetoma Progression

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...

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Bibliographic Details
Published in:	Journal of Immunology Vol. 177; no. 3; pp. 1997 - 2005
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	United States Am Assoc Immnol 01-08-2006
Subjects:	Adult Amino Acid Sequence Animals Antibodies, Fungal - biosynthesis Antibodies, Fungal - blood Antibodies, Neoplasm - biosynthesis Antibodies, Neoplasm - blood Antigens, Fungal - biosynthesis Antigens, Fungal - genetics Antigens, Fungal - isolation & purification Antigens, Neoplasm - biosynthesis Antigens, Neoplasm - genetics Antigens, Neoplasm - isolation & purification Bacteriophage lambda - genetics Bacteriophage lambda - immunology Base Sequence Biomarkers, Tumor - biosynthesis Biomarkers, Tumor - genetics Biomarkers, Tumor - isolation & purification Disease Progression Edible Grain - microbiology Female Gene Library Humans Madurella - genetics Madurella - pathogenicity Madurella mycetomatis Mice Mice, Inbred BALB C Molecular Sequence Data Mycetoma - immunology Mycetoma - microbiology Mycetoma - pathology Protein Biosynthesis - genetics Protein Biosynthesis - immunology Sequence Homology, Amino Acid
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-1767 1550-6606 1365-2567
DOI:	10.4049/jimmunol.177.3.1997