Advanced

Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer

Pin, Elisa; Henjes, Frauke; Hong, Mun Gwan; Wiklund, Fredrik LU ; Magnusson, Patrik; Bjartell, Anders LU ; Uhlén, Mathias; Nilsson, Peter and Schwenk, Jochen M. (2017) In Journal of Proteome Research 16(1). p.204-216
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antigen, autoimmunity, epitope mapping, Human Protein Atlas, peptide, planar microarray, profiling, prostate cancer, prostein, suspension bead array
in
Journal of Proteome Research
volume
16
issue
1
pages
13 pages
publisher
The American Chemical Society
external identifiers
  • scopus:85017653060
  • wos:000391782100019
ISSN
1535-3893
DOI
10.1021/acs.jproteome.6b00620
language
English
LU publication?
yes
id
1fbf1d13-a25b-41e0-87f5-acc3f1dd97b0
date added to LUP
2017-05-08 14:57:06
date last changed
2017-09-18 11:35:26
@article{1fbf1d13-a25b-41e0-87f5-acc3f1dd97b0,
  abstract     = {<p>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.</p>},
  author       = {Pin, Elisa and Henjes, Frauke and Hong, Mun Gwan and Wiklund, Fredrik and Magnusson, Patrik and Bjartell, Anders and Uhlén, Mathias and Nilsson, Peter and Schwenk, Jochen M.},
  issn         = {1535-3893},
  keyword      = {antigen,autoimmunity,epitope mapping,Human Protein Atlas,peptide,planar microarray,profiling,prostate cancer,prostein,suspension bead array},
  language     = {eng},
  month        = {01},
  number       = {1},
  pages        = {204--216},
  publisher    = {The American Chemical Society},
  series       = {Journal of Proteome Research},
  title        = {Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer},
  url          = {http://dx.doi.org/10.1021/acs.jproteome.6b00620},
  volume       = {16},
  year         = {2017},
}