Immunoaffinity Targeted Mass Spectrometry Analysis of Human Plasma Samples Reveals an Imbalance of Active and Inactive CXCL10 in Primary Sjögren's Syndrome Disease Patients

One of the most important advantages of mass spectrometry is the ability to quantify proteins and their modifications in parallel to obtain a holistic picture of the protein of interest. Here, we present a hybrid immunoaffinity targeted mass spectrometry (MS) method that combines efficient pan-antib...

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Veröffentlicht in:Journal of proteome research 2020-10, Vol.19 (10), p.4196-4209
Hauptverfasser: Schmidt, Alexander, Farine, Hervé, Keller, Marcel P, Sebastian, Agata, Kozera, Lukasz, Welford, Richard W D, Strasser, Daniel S
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container_end_page 4209
container_issue 10
container_start_page 4196
container_title Journal of proteome research
container_volume 19
creator Schmidt, Alexander
Farine, Hervé
Keller, Marcel P
Sebastian, Agata
Kozera, Lukasz
Welford, Richard W D
Strasser, Daniel S
description One of the most important advantages of mass spectrometry is the ability to quantify proteins and their modifications in parallel to obtain a holistic picture of the protein of interest. Here, we present a hybrid immunoaffinity targeted mass spectrometry (MS) method that combines efficient pan-antibody enrichment of a specific protein from plasma with the selectivity of high-resolution targeted MS analysis to quantitate specific proteoforms of interest. We used this approach to quantify plasma levels of the chemokine CXCL10 that has been associated with many immunological disorders such as systemic lupus erythematosus and primary Sjögren's Syndrome (pSS). The hybrid approach enabled sensitive, specific, and simultaneous quantification of total, full-length (active) CXCL10 and DPP4-truncated (inactive) CXCL10 in human plasma down to the low pg/mL level, reaching ELISA sensitivities. Samples from 30 control subjects and 34 pSS patients ( = 64) were analyzed. The ratio of CXCL10 to truncated CXCL10 was significantly increased in patients with pSS and provided the highest correlation with pSS disease activity. Therefore, this CXCL10 proteoform ratio represents an interesting exploratory disease activity biomarker to further investigate. As this strategy can be readily adapted to other plasma proteins and proteoforms of interest, we are convinced that it will lead to a more detailed understanding of proteoforms in physiology and pathology yielding more relevant biomarkers and drug targets.
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subjects Biomarkers
Chemokine CXCL10 - genetics
Enzyme-Linked Immunosorbent Assay
Humans
Lupus Erythematosus, Systemic
Mass Spectrometry
Sjogren's Syndrome - diagnosis
Sjogren's Syndrome - genetics
title Immunoaffinity Targeted Mass Spectrometry Analysis of Human Plasma Samples Reveals an Imbalance of Active and Inactive CXCL10 in Primary Sjögren's Syndrome Disease Patients
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