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Identification of a...
Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer
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- Pin, Elisa (author)
- KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab
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- Henjes, Frauke (author)
- KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab
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- Hong, Mun-Gwan (author)
- KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab
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- Wiklund, Fredrik (author)
- Karolinska Institutet,Karolinska Institute
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- Magnusson, Patrik (author)
- Karolinska Institutet,Karolinska Institute
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- Bjartell, Anders (author)
- Lund University,Lunds universitet,Urologisk cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Urological cancer, Malmö,Lund University Research Groups,Skåne University Hospital
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- Uhlén, Mathias (author)
- KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab
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- Nilsson, Peter (author)
- KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab
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- Schwenk, Jochen M. (author)
- KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2016-10-24
- 2017
- English.
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 16:1, s. 204-216
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- autoimmunity
- prostate cancer
- prostein
- planar microarray
- suspension bead array
- profiling epitope mapping
- Human Protein Atlas
- antigen
- peptide
- antigen
- autoimmunity
- epitope mapping
- Human Protein Atlas
- peptide
- planar microarray
- profiling
- prostate cancer
- prostein
- suspension bead array
Publication and Content Type
- ref (subject category)
- art (subject category)
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