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SpotLight Proteomics—A IgG-Enrichment Phenotype Profiling Approach with Clinical Implications

Sarcoidosis is a systemic interstitial lung disease of unknown aetiology. Less invasive diagnostics are needed to decipher disease pathology and to distinguish sub-phenotypes. Here we test if SpotLight proteomics, which combines de novo MS/MS sequencing of enriched IgG and co-extracted proteins with...

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Autores principales: Lundström, Susanna L., Heyder, Tina, Wiklundh, Emil, Zhang, Bo, Eklund, Anders, Grunewald, Johan, Zubarev, Roman A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540603/
https://www.ncbi.nlm.nih.gov/pubmed/31052352
http://dx.doi.org/10.3390/ijms20092157
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author Lundström, Susanna L.
Heyder, Tina
Wiklundh, Emil
Zhang, Bo
Eklund, Anders
Grunewald, Johan
Zubarev, Roman A.
author_facet Lundström, Susanna L.
Heyder, Tina
Wiklundh, Emil
Zhang, Bo
Eklund, Anders
Grunewald, Johan
Zubarev, Roman A.
author_sort Lundström, Susanna L.
collection PubMed
description Sarcoidosis is a systemic interstitial lung disease of unknown aetiology. Less invasive diagnostics are needed to decipher disease pathology and to distinguish sub-phenotypes. Here we test if SpotLight proteomics, which combines de novo MS/MS sequencing of enriched IgG and co-extracted proteins with subsequent label-free quantification of new and known peptides, can differentiate controls and sarcoidosis phenotypes (Löfgrens and non-Löfgrens syndrome, LS and nonLS). Intra-individually matched IgG enriched from serum and bronchial lavage fluid (BALF) from controls (n = 12), LS (n = 11) and nonLS (n = 12) were investigated. High-resolution mass-spectrometry SpotLight proteomics and uni- and multivariate-statistical analyses were used for data processing. Major differences were particularly observed in control-BALF versus sarcoidosis-BALF. However, interestingly, information obtained from BALF profiles was still present (but less prominent) in matched serum profiles. By using information from orthogonal partial least squares discriminant analysis (OPLS-DA) differentiating 1) sarcoidosis-BALF and control-BALF and 2) LS-BALF vs. nonLS-BALF, control-serum and sarcoidosis-serum (p = 0.0007) as well as LS-serum and nonLS-serum (p = 0.006) could be distinguished. Noteworthy, many factors prominent in identifying controls and patients were those associated with Fc-regulation, but also features from the IgG-Fab region and novel peptide variants. Differences between phenotypes were mostly IgG-specificity related. The results support the analytical utility of SpotLight proteomics which prospectively have potential to differentiate closely related phenotypes from a simple blood test.
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spelling pubmed-65406032019-06-04 SpotLight Proteomics—A IgG-Enrichment Phenotype Profiling Approach with Clinical Implications Lundström, Susanna L. Heyder, Tina Wiklundh, Emil Zhang, Bo Eklund, Anders Grunewald, Johan Zubarev, Roman A. Int J Mol Sci Article Sarcoidosis is a systemic interstitial lung disease of unknown aetiology. Less invasive diagnostics are needed to decipher disease pathology and to distinguish sub-phenotypes. Here we test if SpotLight proteomics, which combines de novo MS/MS sequencing of enriched IgG and co-extracted proteins with subsequent label-free quantification of new and known peptides, can differentiate controls and sarcoidosis phenotypes (Löfgrens and non-Löfgrens syndrome, LS and nonLS). Intra-individually matched IgG enriched from serum and bronchial lavage fluid (BALF) from controls (n = 12), LS (n = 11) and nonLS (n = 12) were investigated. High-resolution mass-spectrometry SpotLight proteomics and uni- and multivariate-statistical analyses were used for data processing. Major differences were particularly observed in control-BALF versus sarcoidosis-BALF. However, interestingly, information obtained from BALF profiles was still present (but less prominent) in matched serum profiles. By using information from orthogonal partial least squares discriminant analysis (OPLS-DA) differentiating 1) sarcoidosis-BALF and control-BALF and 2) LS-BALF vs. nonLS-BALF, control-serum and sarcoidosis-serum (p = 0.0007) as well as LS-serum and nonLS-serum (p = 0.006) could be distinguished. Noteworthy, many factors prominent in identifying controls and patients were those associated with Fc-regulation, but also features from the IgG-Fab region and novel peptide variants. Differences between phenotypes were mostly IgG-specificity related. The results support the analytical utility of SpotLight proteomics which prospectively have potential to differentiate closely related phenotypes from a simple blood test. MDPI 2019-05-01 /pmc/articles/PMC6540603/ /pubmed/31052352 http://dx.doi.org/10.3390/ijms20092157 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lundström, Susanna L.
Heyder, Tina
Wiklundh, Emil
Zhang, Bo
Eklund, Anders
Grunewald, Johan
Zubarev, Roman A.
SpotLight Proteomics—A IgG-Enrichment Phenotype Profiling Approach with Clinical Implications
title SpotLight Proteomics—A IgG-Enrichment Phenotype Profiling Approach with Clinical Implications
title_full SpotLight Proteomics—A IgG-Enrichment Phenotype Profiling Approach with Clinical Implications
title_fullStr SpotLight Proteomics—A IgG-Enrichment Phenotype Profiling Approach with Clinical Implications
title_full_unstemmed SpotLight Proteomics—A IgG-Enrichment Phenotype Profiling Approach with Clinical Implications
title_short SpotLight Proteomics—A IgG-Enrichment Phenotype Profiling Approach with Clinical Implications
title_sort spotlight proteomics—a igg-enrichment phenotype profiling approach with clinical implications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540603/
https://www.ncbi.nlm.nih.gov/pubmed/31052352
http://dx.doi.org/10.3390/ijms20092157
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