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9 results on '"Bertrand Toussaint"'

1. Inulin prebiotic reinforces host cancer immunosurveillance via ɣδ T cell activation

Author

Emilie Boucher, Caroline Plazy, Mathias L. Richard, Antonia Suau, Irène Mangin, Muriel Cornet, Delphine Aldebert, Bertrand Toussaint, and Dalil Hannani

Subjects
ɣδ T cells, immunosurveillance, microbiota, prebiotic, inulin, Immunologic diseases. Allergy, RC581-607
Abstract

The gut microbiota is now recognized as a key parameter affecting the host’s anti-cancer immunosurveillance and ability to respond to immunotherapy. Therefore, optimal modulation for preventive and therapeutic purposes is very appealing. Diet is one of the most potent modulators of microbiota, and thus nutritional intervention could be exploited to improve host anti-cancer immunity. Here, we show that an inulin-enriched diet, a prebiotic known to promote immunostimulatory bacteria, triggers an enhanced Th1-polarized CD4+ and CD8+ αβ T cell-mediated anti-tumor response and attenuates tumor growth in three preclinical tumor-bearing mouse models. We highlighted that the inulin-mediated anti-tumor effect relies on the activation of both intestinal and tumor-infiltrating ɣδ T cells that are indispensable for αβ T cell activation and subsequent tumor growth control, in a microbiota-dependent manner. Overall, our data identified these cells as a critical immune subset, mandatory for inulin-mediated anti-tumor immunity in vivo, further supporting and rationalizing the use of such prebiotic approaches, as well as the development of immunotherapies targeting ɣδ T cells in cancer prevention and immunotherapy.

Published
2023
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2. Inulin Prebiotic Protects against Lethal Pseudomonas aeruginosa Acute Infection via γδ T Cell Activation

Author

Emilie Boucher, Caroline Plazy, Audrey Le Gouellec, Bertrand Toussaint, and Dalil Hannani

Subjects
prebiotic, inulin, γδ T cells, Pseudomonas aeruginosa, immunity, gut–lung axis, Nutrition. Foods and food supply, TX341-641
Abstract

Pseudomonas aeruginosa (P. aeruginosa) causes harmful lung infections, especially in immunocompromised patients. The immune system and Interleukin (IL)-17-producing γδ T cells (γδ T) are critical in controlling these infections in mice. The gut microbiota modulates host immunity in both cancer and infection contexts. Nutritional intervention is a powerful means of modulating both microbiota composition and functions, and subsequently the host’s immune status. We have recently shown that inulin prebiotic supplementation triggers systemic γδ T activation in a cancer context. We hypothesized that prophylactic supplementation with inulin might protect mice from lethal P. aeruginosa acute lung infection in a γδ T-dependent manner. C57Bl/6 mice were supplemented with inulin for 15 days before the lethal P. aeruginosa lung infection, administered intranasally. We demonstrate that prophylactic inulin supplementation triggers a higher proportion of γδ T in the blood, accompanied by a higher infiltration of IL-17-producing γδ T within the lungs, and protects 33% of infected mice from death. This observation relies on γδ T, as in vivo γδ TcR blocking using a monoclonal antibody completely abrogates inulin-mediated protection. Overall, our data indicate that inulin supplementation triggers systemic γδ T activation, and could help resolve lung P. aeruginosa infections. Moreover, our data suggest that nutritional intervention might be a powerful way to prevent/reduce infection-related mortality, by reinforcing the microbiota-dependent immune system.

Published
2023
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3. Bioengineering of Escherichia coli Nissle 1917 for Production and Excretion of Spermidine, a Key Metabolite in Human Health

Author

Clément Caffaratti, Caroline Plazy, Valérie Cunin, Bertrand Toussaint, and Audrey Le Gouellec

Subjects
microbiota, immunity, spermidine, metabolic engineering, probiotics, Live Biotherapeutic Product, Microbiology, QR1-502
Abstract

Microbiota-derived metabolites have biological importance for their host. Spermidine, a metabolite described for its protective effect in age-related diseases, is now studied for its role in the resolution of inflammation and gut homeostasis. Strategies to modulate its production in the gastrointestinal tract are of interest to increase host spermidine intakes. Here, we show that metabolic engineering can be used to increase spermidine production by the probiotic Escherichia coli Nissle 1917 (EcN), used in humans. First, we found that increasing the expression of genes involved in polyamine biosynthesis, namely the S-adenosylmethionine synthase speD and the spermidine synthase speE, resulted in an increase in spermidine produced and excreted by our engineered bacteria. The major drawback of this first attempt was the production of acetylated forms of spermidine. Next, we propose to solve this problem by increasing the expression of the spermidine exporter system MdtI/MdtJ. This second strategy had a major impact on the spermidine profile found in the culture supernatant. Our results demonstrate, for the first time, the feasibility of rationally engineering bacterial probiotic strains to increase their ability to deliver the microbiota-derived metabolite, spermidine. This work illustrates how metabolomic and synthetic biology can be used to design and improve engineered Live Biotherapeutic Products that have the potential to be used in personalized medicine.

Published
2022
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4. What clinical metabolomics will bring to the medicine of tomorrow

Author

Audrey Le Gouellec, Caroline Plazy, and Bertrand Toussaint

Abstract

The purpose of this review is to explore how clinical metabolomics could help physicians in the future. The recent advent of medical genomics brings new and interesting technological tools to measure genetic predispositions to a disease. But metabolomics will allow us to go even further by linking the patient’s pathological phenotype with gene expression defects and metabolic disorders. It is in this context that the clinical chemist must adapt and be a force of proposal to meet these health challenges. He must help the clinician by mastering these new innovative tools, in order to participate in the implementation of clinical studies for the discovery of biomarkers, but also to propose the assays of biomarkers called “signatures,” which can be composite biomarkers or fingerprints, which will ultimately guide the clinician. He will have to propose them as clinical chemistry tests. In the first part, we will look at some concrete examples of the use of clinical metabolomics in clinical research projects that have led to the identification of a new biomarker. We will use the example of trimethylamine N-oxide (or TMAO) and review the clinical studies that have proposed TMAO as a biomarker for cardiovascular diseases. In a second part, we will see through bibliographic studies, how the metabolomic fingerprint can be useful to build a supervised model for patient stratification. In conclusion, we will discuss the limitations currently under debate.

Published
2023
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5. The onset of late severe lung impairment in COVID-19 is associated with high inflammation markers at admission and metabolic syndrome markers

Author

Olivier Epaulard, Audrey Le Gouellec, Marion Le Marechal, Benjamin Nemoz, Anne-Laure Borel, Anaïs Dartevel, Hubert Gheerbrant, Marie-Christine Herault, Annick Bosseray, Giovanna Clavarino, Julien Lupo, Damien Viglino, Fanny Quenard, Clara Candille, Boubou Camara, Michel Durand, Patrice Faure, Dorra Guergour, Elena Chidlovski, Marie-Christine Jacob, Sylvie Larrat, Marie Froidure, Nicolas Terzi, Sébastien Quetant, Jean-François Payen, Barbara Colombe, Tatiana Raskovalova, Patrice Morand, Isabelle Pierre, Carole Schwebel, Rebecca Hamidfar, Laurence Bouillet, Jean-Paul Brion, Candice Trocme, Sylvie Berthier, Carole Chirica, Anne-Laure Mounayar, Myriam Blanc, Patricia Pavese, and Bertrand Toussaint

Abstract

BackgroundCOVID-19 severity is mainly related to lung impairment. However, preexisting patient characteristics and biomarkers at admission associated with this event are not precisely known.MethodsWe report 205 patients admitted for a proven COVID-19 in our institution between March 7 and April 22, 2020, particularly their comorbidities, respiratory severity, immune profile, and metabolic profile.FindingsMedian age was 70 years [interquartile range (IQR) 25-75: 60;79]; 115 (56·1%) patients were men. Oxygen supplementation of >2L/min was required in 107 patients (52·2%) after a median time of 8 days [IQR: 6;10] after the first symptoms; 67 (32·7%) patients were admitted to the intensive care unit (ICU), almost exclusively due to severe hypoxia. Patients requiring >2L/min oxygen therapy and/or ICU admission were older and more frequently males, with a significantly higher body mass index (BMI), a significantly higher total cholesterol (TC) / HDL cholesterol ratio, and higher triglycerides. They also had higher plasma levels of C-reactive protein (CRP) and interleukin 6 (IL-6); IL-6 >20 ng/L and CRP >70 mg/L were significantly associated with ICU admission and/or (for patients with a decision of limitation of life-support therapy) death. Higher BMI and TC/HDL-c ratio were associated with higher CRP and IL-6 levels. Steroid therapy was performed in 61 patients; while its clinical impact was inconclusive due to heterogeneous situations, IL-6 levels decreased significantly more in these patients.InterpretationSevere COVID-19 mostly relates to late-onset pneumonia associated with preexisting metabolic syndrome markers and a surge in inflammatory markers, allowing the early identification of at-risk patients.FundingThis work was supported by Foundation University of Grenoble Alpes.

Published
2022

6. Inulin prebiotic reinforces host cancer immunosurveillance via γδ T cell activation

Author

Emilie Boucher, Caroline Plazy, Mathias L. Richard, Antonia Suau, Irène Mangin, Muriel Cornet, Delphine Aldebert, Bertrand Toussaint, Dalil Hannani, Translational microbial Evolution and Engineering (TIMC-TrEE), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Paris Center for Microbiome Medicine (FHU PaCeMM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Metabiot (Metabiot), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), and Centre Hospitalier Universitaire [Grenoble] (CHU)

Subjects
host cancer, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, cell activation
Abstract

The gut microbiota is now recognized as a key parameter affecting the host’s anti-cancer immunosurveillance and ability to respond to immunotherapy. Therefore, optimal modulation for preventive and therapeutic purposes is very appealing. Diet is one of the most potent modulators of microbiota, and thus nutritional intervention could be exploited to improve host anti-cancer immunity. Here, we show that an inulin-enriched diet, a prebiotic known to promote immunostimulatory bacteria, triggers an enhanced Th1-polarized CD4+and CD8+αβ T cell-mediated anti-tumor response and attenuates tumor growth in three preclinical tumor-bearing mouse models. We highlighted that the inulin-mediated anti-tumor effect relies on the activation of both intestinal and tumor-infiltrating γδ T cells that are indispensable for αβ T cell activation and subsequent tumor growth control, in a microbiota-dependent manner. Overall, our data identified these cells as a critical immune subset, mandatory for inulin-mediated anti-tumor immunityin vivo, further supporting and rationalizing the use of such prebiotic approaches, as well as the development of immunotherapies targeting γδ T cells in cancer prevention and immunotherapy.SignificanceOur study reveals that γδ T cells anti-cancer activity can be improved by nutritional intervention, in a microbiota-dependent manner. This work also indicates that γδ T cells are indispensable for reinforcing αβ T cells cancer immunosurveillance and subsequent tumor growth control. We believe that these findings could be of interest to the field of gut microbiota modulation, rationalizing the use of such prebiotic approaches as well as γδ T cells targeting, in cancer prevention and immunotherapy.

Published
2022

7. Bioengineering of Escherichia coli Nissle 1917 for Overproduction and Excretion of Spermidine, a Key Metabolite in Human Health

Author

Clement Caffaratti, Caroline Plazy, Valérie Cunin, Bertrand Toussaint, and Audrey Le Gouellec

Abstract

Over the past decade, studies have demonstrated the importance of bioactive metabolites derived from the microbiota in the regulation of physiological processes essential for homeostasis and the maintenance of human health. Strategies to modulate the production of these metabolites in the gastrointestinal tract hold promise for combating dysbiosis or inflammatory bowel disease. Metabolic engineering of probiotics could be one of these solutions. In this work, we engineered Escherichia coli Nissle 1917 (EcN) to overproduce spermidine, a metabolite known for its anti-immunosenescence and anti-inflammatory properties. Using a rational synthetic biology approach coupled with analysis by high resolution mass spectrometry, we designed in several steps and validated engineered probiotics overproducing and excreting spermidine. Based on our results, we first added the enzyme substrate putrescine and showed the overproduction of spermidine and decided to add a transporter limiting the production of the acetylated form of spermidine. Next, we used untargeted metabolomics to study the impact of engineering on the central metabolism of E. coli Nissle. Untargeted metabolomics appears to be a good strategy to optimize the metabolic engineering of probiotic strains and thus accelerate their development for personalized medicine.

Published
2022

8. Bioengineering of

Author

Clément, Caffaratti, Caroline, Plazy, Valérie, Cunin, Bertrand, Toussaint, and Audrey, Le Gouellec

Abstract

Microbiota-derived metabolites have biological importance for their host. Spermidine, a metabolite described for its protective effect in age-related diseases, is now studied for its role in the resolution of inflammation and gut homeostasis. Strategies to modulate its production in the gastrointestinal tract are of interest to increase host spermidine intakes. Here, we show that metabolic engineering can be used to increase spermidine production by the probiotic

Published
2022

9. Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study

Author

Michael Levraut, Sabine Laurent-Chabalier, Xavier Ayrignac, Kévin Bigaut, Manon Rival, Sanae Squalli, Hélène Zéphir, Tifanie Alberto, Jean-David Pekar, Jonathan Ciron, Damien Biotti, Bénédicte Puissant-Lubrano, Jean-Philippe Camdessanché, Yannick Tholance, Olivier Casez, Bertrand Toussaint, Jeanne Marion, Thibault Moreau, Daniela Lakomy, Audrey Thomasset, Elisabeth Maillart, Delphine Sterlin, Aude Maurousset, Auriane Rocher, David Axel Laplaud, Edith Bigot-Corbel, Pierre-Olivier Bertho, Jean Pelletier, Joseph Boucraut, Pierre Labauge, Thierry Vincent, Jérôme De Sèze, Isabelle Jahn, Barbara Seitz-Polski, Eric Thouvenot, Christine Lebrun-Frenay, Université Côte d'Azur - Faculté de Médecine (UCA Faculté Médecine), Université Côte d'Azur (UCA), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Les Hôpitaux Universitaires de Strasbourg (HUS), Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), Laboratoire de Biochimie [CHRU Nîmes], Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pôle Neurosciences [CHU Toulouse], Institut Fédératif de Biologie (IFB), Service de Neurologie [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Universitaire [Grenoble] (CHU), Translational microbial Evolution and Engineering (TIMC-TrEE), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service de Biochimie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Team 5 : Neuroinflammation, mechanisms, therapeutic options (NEMO) (U1064 Inserm - CR2TI), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Laboratoire de Biochimie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Département de Biochimie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Nord Laennec [CHU Nantes], Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Strasbourg, Laboratoire Immunologie [Nice], Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Hôpital de l'Archet-Université Côte d'Azur (UCA), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Société Francophone de la Sclérose En Plaques (SFSEP)., and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
MESH: Humans, MESH: Multiple Sclerosis, Multiple Sclerosis, MESH: Demyelinating Diseases* / diagnosis, [SDV]Life Sciences [q-bio], Oligoclonal Bands, MESH: Immunoglobulin kappa-Chains, MESH: Central Nervous System Diseases, MESH: Oligoclonal Bands, Cohort Studies, Immunoglobulin kappa-Chains, Neurology, Central Nervous System Diseases, MESH: Biomarkers, Humans, Female, Neurology (clinical), MESH: Cohort Studies, MESH: Female, Biomarkers, Demyelinating Diseases
Abstract

Background and ObjectivesKappa free light chains (KFLC) seem to efficiently diagnose MS. However, extensive cohort studies are lacking to establish consensus cut-offs, notably to rule out non-MS autoimmune CNS disorders. Our objectives were to (1) determine diagnostic performances of CSF KFLC, KFLC index, and KFLC intrathecal fraction (IF) threshold values that allow us to separate MS from different CNS disorder control populations and compare them with oligoclonal bands' (OCB) performances and (2) to identify independent factors associated with KFLC quantification in MS.MethodsWe conducted a retrospective multicenter study involving 13 French MS centers. Patients were included if they had a noninfectious and nontumoral CNS disorder, eligible data concerning CSF and serum KFLC, albumin, and OCB. Patients were classified into 4 groups according to their diagnosis: MS, clinically isolated syndrome (CIS), other inflammatory CNS disorders (OIND), and noninflammatory CNS disorder controls (NINDC).ResultsOne thousand six hundred twenty-one patients were analyzed (675 MS, 90 CIS, 297 OIND, and 559 NINDC). KFLC index and KFLC IF had similar performances in diagnosing MS from nonselected controls and OIND (p= 0.123 andp= 0.991 for area under the curve [AUC] comparisons) and performed better than CSF KFLC (p< 0.001 for all AUC comparisons). A KFLC index of 8.92 best separated MS/CIS from the entire nonselected control population, with better performances than OCB (p< 0.001 for AUC comparison). A KFLC index of 11.56 best separated MS from OIND, with similar performances than OCB (p= 0.065). In the multivariate analysis model, female gender (p= 0.003), young age (p= 0.013), and evidence of disease activity (p< 0.001) were independent factors associated with high KFLC index values in patients with MS, whereas MS phenotype, immune-modifying treatment use at sampling, and the FLC analyzer type did not influence KFLC index.DiscussionKFLC biomarkers are efficient tools to separate patients with MS from controls, even when compared with other patients with CNS autoimmune disorder. Given these results, we suggest using KFLC index or KFLC IF as a criterion to diagnose MS.Classification of EvidenceThis study provides Class III evidence that KFLC index or IF can be used to differentiate patients with MS from nonselected controls and from patients with other autoimmune CNS disorders.

Published
2022

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