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J Immunol. 2014 Sep 15;193(6):3146-54. doi: 10.4049/jimmunol.1303098. Epub 2014 Aug 13.

Secretion and immunogenicity of the meningioma-associated antigen TXNDC16.

Author information

1
Department of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
2
Buck Institute for Age Research, Novato, CA 94945;
3
Department of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany; Chair for Clinical Bioinformatics, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
4
Institute for Clinical and Experimental Surgery, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
5
Department of Physiology, Medical School, Saarland University, 66421 Homburg, Germany; and.
6
Medical Biochemistry and Molecular Biology, Medical School, Saarland University, 66421 Homburg/Saar, Germany.
7
Chair for Clinical Bioinformatics, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
8
Department of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany; hgemee@uks.eu.

Abstract

In a previous study, we identified thioredoxin domain containing 16 (TXNDC16) as a meningioma-associated Ag by protein macroarray screening. Serological screening detected autoantibodies against TXNDC16 exclusively in meningioma patients' sera and not in sera of healthy controls. TXNDC16 was previously found to be an endoplasmic reticulum (ER)-luminal glycoprotein. In this study, we show an additional ER-associated localization of TXNDC16 in the cytosol by in vitro synthesis, molecular mass shift assay, and flow cytometry. We were able to show TXNDC16 secretion in different human cell lines due to masked and therefore nonfunctional ER retrieval motif. A previously indicated exosomal TXNDC16 secretion could not be confirmed in HEK293 cells. The secreted serum protein TXNDC16 is bound in circulating immune complexes, which were found both in meningioma and healthy blood donor sera. Employing a customized array with 163 overlapping TXNDC16 peptides and measuring autoantibody reactivity, we achieved discrimination of meningioma sera from healthy controls with an accuracy of 87.2% using a set of only five immunogenic TXNDC16 epitopes.

PMID:
25122923
DOI:
10.4049/jimmunol.1303098
[Indexed for MEDLINE]
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