Inflammatory mediators, lipoproteins and apolipoproteins in early diagnosis of amyotrophic lateral sclerosis

There is currently no diagnostic or prognostic biomarker available in clinical practice for Amyotrophic Lateral Sclerosis (ALS). The objective of this study was to monitor a combination of various inflammatory markers, lipids, and apolipoproteins alterations in ALS patients at the time of diagnosis,...

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Main Authors: Hugo Alarcan, Mélanie Berthet, Laura Suire, Corentin Colas, Loïc Gonzalez, Christophe Paget, Isabelle Benz-de Bretagne, Eric Piver, Patrick Vourc'h, Christian Andres, Philippe Corcia, Hélène Blasco
Format: Article
Language:English
Published: Elsevier 2022-10-01
Series:SLAS Technology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2472630322051652
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author Hugo Alarcan
Mélanie Berthet
Laura Suire
Corentin Colas
Loïc Gonzalez
Christophe Paget
Isabelle Benz-de Bretagne
Eric Piver
Patrick Vourc'h
Christian Andres
Philippe Corcia
Hélène Blasco
author_facet Hugo Alarcan
Mélanie Berthet
Laura Suire
Corentin Colas
Loïc Gonzalez
Christophe Paget
Isabelle Benz-de Bretagne
Eric Piver
Patrick Vourc'h
Christian Andres
Philippe Corcia
Hélène Blasco
author_sort Hugo Alarcan
collection DOAJ
description There is currently no diagnostic or prognostic biomarker available in clinical practice for Amyotrophic Lateral Sclerosis (ALS). The objective of this study was to monitor a combination of various inflammatory markers, lipids, and apolipoproteins alterations in ALS patients at the time of diagnosis, to assess their role as early diagnostic or prognostic biomarker candidates. C-reactive protein, orosomucoid, prealbumin, calprotectin, lipids and apoliproteins were determined in the blood of all subjects (25 ALS patients, 23 controls) as routinely performed in our laboratory. Inflammatory mediators were evaluated by a bead-based multiplex assay. A two-step approach was used for each analytical strategy: univariate analysis followed by multivariate analysis. Eight features were significantly different between ALS patients and controls, sometimes with important fold changes. The supervised Partial least Squares Discriminant Analysis separated ALS and controls with great accuracy (94 %) and the permutation test was significant (p < 0.01), ensuring the robustness of the model. The prediction model leads to a mean sensitivity and specificity of 90 (+/- 10) and 78 (+/- 10) %, respectively, with a mean predictive positive value and negative predictive value of 80 (+/- 8.9) and 89 (+/- 11.8) %, respectively. However, the models did not discriminate subgroups of ALS patients based on ALS characteristics. This study highlights the usefulness of evaluating a combination of multiple pathways rather than focusing on a single target. These promising results suggest the need for the longitudinal monitoring of these candidates to determine their role in disease evolution.
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spelling doaj.art-4b0344ff01fa407e8e2260af0b16eab32022-12-22T04:29:38ZengElsevierSLAS Technology2472-63032022-10-01275327334Inflammatory mediators, lipoproteins and apolipoproteins in early diagnosis of amyotrophic lateral sclerosisHugo Alarcan0Mélanie Berthet1Laura Suire2Corentin Colas3Loïc Gonzalez4Christophe Paget5Isabelle Benz-de Bretagne6Eric Piver7Patrick Vourc'h8Christian Andres9Philippe Corcia10Hélène Blasco11Laboratoire de biochimie et biologie moléculaire, CHRU Bretonneau, 2 Boulevard Tonnellé, 37000 Tours, France; Corresponding author.Laboratoire de biochimie et biologie moléculaire, CHRU Bretonneau, 2 Boulevard Tonnellé, 37000 Tours, FranceLaboratoire de biochimie, CHRU Trousseau, avenue de la République, 37170 Chambray-lès-Tours, FranceLaboratoire de biochimie et biologie moléculaire, CHRU Bretonneau, 2 Boulevard Tonnellé, 37000 Tours, FranceUMR1100 « Infection respiratoire &amp; Immunité », Université de Tours, Inserm, 10 Boulevard Tonnellé, 37000 Tours, FranceUMR1100 « Infection respiratoire &amp; Immunité », Université de Tours, Inserm, 10 Boulevard Tonnellé, 37000 Tours, FranceLaboratoire de biochimie, CHRU Trousseau, avenue de la République, 37170 Chambray-lès-Tours, FranceLaboratoire de biochimie, CHRU Trousseau, avenue de la République, 37170 Chambray-lès-Tours, FranceLaboratoire de biochimie et biologie moléculaire, CHRU Bretonneau, 2 Boulevard Tonnellé, 37000 Tours, France; UMR 1253 iBrain, Université de Tours, Inserm, 10 Boulevard Tonnellé, 37000 Tours, FranceLaboratoire de biochimie et biologie moléculaire, CHRU Bretonneau, 2 Boulevard Tonnellé, 37000 Tours, France; UMR 1253 iBrain, Université de Tours, Inserm, 10 Boulevard Tonnellé, 37000 Tours, FranceUMR 1253 iBrain, Université de Tours, Inserm, 10 Boulevard Tonnellé, 37000 Tours, France; Service de neurologie, CHRU Bretonneau, 2 Boulevard Tonnellé, 37000 Tours, FranceLaboratoire de biochimie et biologie moléculaire, CHRU Bretonneau, 2 Boulevard Tonnellé, 37000 Tours, France; UMR 1253 iBrain, Université de Tours, Inserm, 10 Boulevard Tonnellé, 37000 Tours, FranceThere is currently no diagnostic or prognostic biomarker available in clinical practice for Amyotrophic Lateral Sclerosis (ALS). The objective of this study was to monitor a combination of various inflammatory markers, lipids, and apolipoproteins alterations in ALS patients at the time of diagnosis, to assess their role as early diagnostic or prognostic biomarker candidates. C-reactive protein, orosomucoid, prealbumin, calprotectin, lipids and apoliproteins were determined in the blood of all subjects (25 ALS patients, 23 controls) as routinely performed in our laboratory. Inflammatory mediators were evaluated by a bead-based multiplex assay. A two-step approach was used for each analytical strategy: univariate analysis followed by multivariate analysis. Eight features were significantly different between ALS patients and controls, sometimes with important fold changes. The supervised Partial least Squares Discriminant Analysis separated ALS and controls with great accuracy (94 %) and the permutation test was significant (p < 0.01), ensuring the robustness of the model. The prediction model leads to a mean sensitivity and specificity of 90 (+/- 10) and 78 (+/- 10) %, respectively, with a mean predictive positive value and negative predictive value of 80 (+/- 8.9) and 89 (+/- 11.8) %, respectively. However, the models did not discriminate subgroups of ALS patients based on ALS characteristics. This study highlights the usefulness of evaluating a combination of multiple pathways rather than focusing on a single target. These promising results suggest the need for the longitudinal monitoring of these candidates to determine their role in disease evolution.http://www.sciencedirect.com/science/article/pii/S2472630322051652Amyotrophic lateral sclerosisLipidsApolipoproteinsInflammatory mediatorsPLS-DA
spellingShingle Hugo Alarcan
Mélanie Berthet
Laura Suire
Corentin Colas
Loïc Gonzalez
Christophe Paget
Isabelle Benz-de Bretagne
Eric Piver
Patrick Vourc'h
Christian Andres
Philippe Corcia
Hélène Blasco
Inflammatory mediators, lipoproteins and apolipoproteins in early diagnosis of amyotrophic lateral sclerosis
SLAS Technology
Amyotrophic lateral sclerosis
Lipids
Apolipoproteins
Inflammatory mediators
PLS-DA
title Inflammatory mediators, lipoproteins and apolipoproteins in early diagnosis of amyotrophic lateral sclerosis
title_full Inflammatory mediators, lipoproteins and apolipoproteins in early diagnosis of amyotrophic lateral sclerosis
title_fullStr Inflammatory mediators, lipoproteins and apolipoproteins in early diagnosis of amyotrophic lateral sclerosis
title_full_unstemmed Inflammatory mediators, lipoproteins and apolipoproteins in early diagnosis of amyotrophic lateral sclerosis
title_short Inflammatory mediators, lipoproteins and apolipoproteins in early diagnosis of amyotrophic lateral sclerosis
title_sort inflammatory mediators lipoproteins and apolipoproteins in early diagnosis of amyotrophic lateral sclerosis
topic Amyotrophic lateral sclerosis
Lipids
Apolipoproteins
Inflammatory mediators
PLS-DA
url http://www.sciencedirect.com/science/article/pii/S2472630322051652
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