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SpotLight Proteomic...
SpotLight Proteomics-A IgG-Enrichment Phenotype Profiling Approach with Clinical Implications
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- Lundstrom, SL (författare)
- Karolinska Institutet
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Heyder, T (författare)
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- Wiklundh, E (författare)
- Karolinska Institutet
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Zhang, B (författare)
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Eklund, A (författare)
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- Grunewald, J (författare)
- Karolinska Institutet
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- Zubarev, RA (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2019-05-01
- 2019
- Engelska.
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 20:9
- Relaterad länk:
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https://www.mdpi.com...
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http://kipublication...
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https://doi.org/10.3...
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Abstract
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- 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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