title: Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer.
abstract: There is a demand for novel targets and approaches to diagnose and treat prostate cancer (PCA). In this context, serum and plasma samples from a total of 609 individuals from two independent patient cohorts were screened for IgG reactivity against a sum of 3833 human protein fragments. Starting from planar protein arrays with 3786 protein fragments to screen 80 patients with and without PCA diagnosis, 161 fragments (4%) were chosen for further analysis based on their reactivity profiles. Adding 71 antigens from literature, the selection of antigens was corroborated for their reactivity in a set of 550 samples using suspension bead arrays. The antigens prostein (SLC45A3), TATA-box binding protein (TBP), and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) showed higher reactivity in PCA patients with late disease compared with early disease. Because of its prostate tissue specificity, we focused on prostein and continued with mapping epitopes of the 66-mer protein fragment using patient samples. Using bead-based assays and 15-mer peptides, a minimal peptide epitope was identified and refined by alanine scanning to the KPxAPFP. Further sequence alignment of this motif revealed homology to transmembrane protein 79 (TMEM79) and TGF-beta-induced factor 2 (TGIF2), thus providing a reasoning for cross-reactivity found in females. A comprehensive workflow to discover and validate IgG reactivity against prostein and homologous targets in human serum and plasma was applied. This study provides useful information when searching for novel biomarkers or drug targets that are guided by the reactivity of the immune system against autoantigens.
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology , 171 65 Solna, Sweden.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pin
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology , 171 65 Solna, Sweden.
authors.forename: Frauke
authors.initials: F
authors.lastname: Henjes
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology , 171 65 Solna, Sweden.
authors.forename: Mun-Gwan
authors.initials: MG
authors.lastname: Hong
authors.affiliation: Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet , 171 77 Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.affiliation: Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet , 171 77 Stockholm, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Magnusson
authors.affiliation: Department of Translational Medicine, Division of Urological Cancers, Skåne University Hospital Malmö, Lund University , 205 02 Malmö, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology , 171 65 Solna, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology , 171 65 Solna, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology , 171 65 Solna, Sweden.
authors.forename: Jochen M
authors.initials: JM
authors.lastname: Schwenk
mesh_terms: D000368:Aged; D020816:Amino Acid Motifs; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000737:chemistry; D015551:Autoimmunity; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000276:immunology; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D003429:Cross Reactions; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000737:chemistry; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D040081:Protein Array Analysis; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D035181:TATA-Box Binding Protein / Q000235:genetics* / Q000276:immunology
chemical_list: D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D000939:Epitopes; D018398:Homeodomain Proteins; D007074:Immunoglobulin G; D008565:Membrane Proteins; D012097:Repressor Proteins; D035181:TATA-Box Binding Protein; C509817:TBP protein, human; C414585:TGIF2 protein, human; C585426:Tmem79 protein, human; C422655:prostein; D007335:Insulin-Like Growth Factor II
keywords: Human Protein Atlas; antigen; autoimmunity; epitope mapping; peptide; planar microarray; profiling; prostate cancer; prostein; suspension bead array