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

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Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer. / Pin, Elisa; Henjes, Frauke; Hong, Mun Gwan; Wiklund, Fredrik; Magnusson, Patrik; Bjartell, Anders; Uhlén, Mathias; Nilsson, Peter; Schwenk, Jochen M.

In: Journal of Proteome Research, Vol. 16, No. 1, 06.01.2017, p. 204-216.

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Pin, E, Henjes, F, Hong, MG, Wiklund, F, Magnusson, P, Bjartell, A, Uhlén, M, Nilsson, P & Schwenk, JM 2017, 'Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer', Journal of Proteome Research, vol. 16, no. 1, pp. 204-216. https://doi.org/10.1021/acs.jproteome.6b00620

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Pin, Elisa ; Henjes, Frauke ; Hong, Mun Gwan ; Wiklund, Fredrik ; Magnusson, Patrik ; Bjartell, Anders ; Uhlén, Mathias ; Nilsson, Peter ; Schwenk, Jochen M. / Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer. In: Journal of Proteome Research. 2017 ; Vol. 16, No. 1. pp. 204-216.

RIS

TY - JOUR

T1 - Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer

AU - Pin, Elisa

AU - Henjes, Frauke

AU - Hong, Mun Gwan

AU - Wiklund, Fredrik

AU - Magnusson, Patrik

AU - Bjartell, Anders

AU - Uhlén, Mathias

AU - Nilsson, Peter

AU - Schwenk, Jochen M.

PY - 2017/1/6

Y1 - 2017/1/6

N2 - 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.

AB - 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.

KW - antigen

KW - autoimmunity

KW - epitope mapping

KW - Human Protein Atlas

KW - peptide

KW - planar microarray

KW - profiling

KW - prostate cancer

KW - prostein

KW - suspension bead array

UR - http://www.scopus.com/inward/record.url?scp=85017653060&partnerID=8YFLogxK

U2 - 10.1021/acs.jproteome.6b00620

DO - 10.1021/acs.jproteome.6b00620

M3 - Article

VL - 16

SP - 204

EP - 216

JO - Journal of Proteome Research

T2 - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 1

ER -