title: Secretion and immunogenicity of the meningioma-associated antigen TXNDC16.
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.
authors.affiliation: Department of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Harz
authors.affiliation: Department of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
authors.forename: Nicole
authors.initials: N
authors.lastname: Ludwig
authors.affiliation: Buck Institute for Age Research, Novato, CA 94945;
authors.forename: Sven
authors.initials: S
authors.lastname: Lang
authors.affiliation: Department of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
authors.forename: Tamara V
authors.initials: TV
authors.lastname: Werner
authors.affiliation: Department of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany; Chair for Clinical Bioinformatics, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
authors.forename: Valentina
authors.initials: V
authors.lastname: Galata
authors.affiliation: Department of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany; Chair for Clinical Bioinformatics, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.affiliation: Department of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
authors.forename: Katja
authors.initials: K
authors.lastname: Schmitt
authors.affiliation: Institute for Clinical and Experimental Surgery, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
authors.forename: Ruth
authors.initials: R
authors.lastname: Nickels
authors.affiliation: Department of Physiology, Medical School, Saarland University, 66421 Homburg, Germany; and.
authors.forename: Elmar
authors.initials: E
authors.lastname: Krause
authors.affiliation: Medical Biochemistry and Molecular Biology, Medical School, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Jung
authors.affiliation: Department of Physiology, Medical School, Saarland University, 66421 Homburg, Germany; and.
authors.forename: Jens
authors.initials: J
authors.lastname: Rettig
authors.affiliation: Chair for Clinical Bioinformatics, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
authors.affiliation: Institute for Clinical and Experimental Surgery, Medical School, Saarland University, 66421 Homburg/Saar, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Menger
authors.affiliation: Medical Biochemistry and Molecular Biology, Medical School, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: Department of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany; hgemee@uks.eu.
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
mesh_terms: D000595:Amino Acid Sequence; D000936:Antigen-Antibody Complex / Q000097:blood*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D008579:Meningioma / Q000276:immunology*; D008969:Molecular Sequence Data
chemical_list: D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D001323:Autoantibodies; D000939:Epitopes; D008562:Membrane Glycoproteins; C000593135:TXNDC16 protein, human