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1. Point-of-Care Periodontitis Testing: Biomarkers, Current Technologies, and Perspectives.

Author

He W, You M, Wan W, Xu F, Li F, and Li A

Subjects
Humans, Time Factors, Biomarkers analysis, Diagnostic Tests, Routine methods, Periodontitis diagnosis, Point-of-Care Systems
Abstract

Periodontitis has become one of the most universal chronic inflammatory diseases worldwide. Subclinical symptom progression, ultimately leading to permanent damage, calls for early diagnosis and long-term monitoring. However, traditional clinical diagnostic methods are complex and expensive, and cannot meet these requirements. Recently, with more biomarkers and the development of new technologies, various point-of-care testing (POCT) platforms have been developed for periodontitis diagnosis and monitoring. These are easy to perform, rapid, low-cost, and are perfectly suited for high-frequency diagnosis of periodontitis at the point-of-care (POC). We summarize existing biomarkers of different periodontitis stages and recent developed POCT platforms (including lab-on-a-chip, paper-based platforms, and chairside tests), discuss their existing challenges and future potential, and provide some inspiration and guidelines for future POC periodontitis testing., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
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2. Tau protein as a possible marker of cerebrospinal fluid leakage in cerebrospinal fluid rhinorrhoea: A pilot study.

Author

Oudart JB, Zucchini L, Maquart FX, Dubernard X, Labrousse M, Fiabane G, Quedreux A, Litre F, and Ramont L

Subjects
Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Pilot Projects, Young Adult, Biomarkers metabolism, Cerebrospinal Fluid Leak metabolism, Cerebrospinal Fluid Rhinorrhea metabolism, tau Proteins metabolism
Abstract

Introduction: The management of posttraumatic cerebrospinal fluid (CSF) rhinorrhoea remains a clinical challenge. Cerebrospinal fistula is a dural defect responsible for possible CSF leakage into the contiguous air-filled cavities located at the skull base. The risk of central nervous system infection in these conditions is severe and can be life threatening. Consequently, a specific CSF biomarker might be used in case of difficult diagnosis of CSF rhinorrhoea. CSF Tau protein is a neuronal protein, commonly assessed for diagnosis of Alzheimer Disease (AD). The aim of this study was to determine whether the Tau protein could be a relevant marker of CSF leakage., Materials and Methods: Tau protein measurement was performed by enzyme-linked immunosorbent assay in 13 patients with CSF leakage (CSF rhinorrhoea group), and 8 patients with spontaneous aqueous rhinorrhoea (non-CSF leakage group). The serum concentration of Tau protein was measured by ELISA in both CSF rhinorrhoea group and non-CSF leakage group., Results: In patients with CSF leakage, CSF Tau protein median concentration was 479 ng/L (197 - 2325 ng/L). On the other hand, the Tau protein concentration was below the lower limit of quantification (LLoQ) (< 87 ng/L) in non-CSF leakage group. Serum Tau protein concentration by ELISA was also below LLoQ (< 87 ng/L) for all subjects., Conclusion: ELISA measurement of Tau protein in rhinorrhoea fluid may be a reliable and relevant marker for detecting the presence of CSF in the nasal discharge and sign the existence of a CSF leakage., Competing Interests: Potential conflict of interest: None declared.

Published
2017
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3. Relationship between endothelin-1 levels and pulmonary arterial hypertension in HIV-infected patients.

Author

Feijoo MQ, Toro R, López Vazquez de la Torre M, Lennie V, Arce C, Moreno V, Valencia E, Vispo E, Almería C, Mangas A, and Carbonero LM

Subjects
Adult, Case-Control Studies, Female, Humans, Hypertension, Pulmonary pathology, Male, Middle Aged, Biomarkers blood, Endothelin-1 blood, HIV Infections complications, Hypertension, Pulmonary epidemiology
Abstract

Objective: Pulmonary arterial hypertension (PAH) is a progressive, fatal disease with average survival of less than 3 years if left untreated. It is most common in patients infected with HIV. Although the pathogenesis in this population is not fully understood, it is thought that HIV infection, through the immune response and release of different inflammatory mediators such as endothelin-1, may contribute directly to endothelial damage. Our objective was to quantify endothelin-1 levels in HIV-infected patients and determine whether or not there is an association between this marker and PAH., Design: A case-control study in patients attending an infectious diseases clinic., Methods: The sample was composed of 79 patients divided into three groups: 23 HIV patients with PAH (HIV+/PAH+), 45 HIV patients without PAH (HIV+/PAH-) and a control group of 11 healthy individuals. The ratio between the HIV+/PAH- and HIV+/PAH+ groups was 2 : 1. Patients were matched by age, sex, risk group and viral load; the control group by age and sex. All patients had blood taken for endothelin-1 plasma quantification., Results: We found lower endothelin-1 levels in the controls than in the HIV+/PAH- group [0.71 pg/ml (interquartile range, IQR 0.54-0.94) vs. 1.13 pg/ml (IQR 0.87-1.38); P = 0.005] and the HIV+/PAH+ cohort [1.16 pg/ml (IQR 0.86-2.37); P = 0.003]. Patients with severe PAH had higher endothelin-1 levels [2.94 pg/ml (IQR 1.81-6.33)] than patients with mild and moderate PAH., Conclusion: Plasma endothelin-1 levels are higher in HIV patients with PAH than in the HIV-noninfected population and levels increase with the severity of the PAH.

Published
2014
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5. Cross-sectional comparisons of dietary indexes underlying nutrition labels: nutri-score, Canadian 'high in' labels and Diabetes Canada Clinical Practices (DCCP).

Author

Paper, Laura, Ahmed, Mavra, Lee, Jennifer J., Kesse-Guyot, Emmanuelle, Touvier, Mathilde, Hercberg, Serge, Galan, Pilar, Salanave, Benoît, Verdot, Charlotte, L'Abbé, Mary R., Deschamps, Valérie, and Julia, Chantal

Subjects
*BIOMARKERS, *FOOD labeling, *NUTRITIONAL value, *CROSS-sectional method, *DIET, *NUTRITIONAL requirements, *MEDICAL protocols, *DESCRIPTIVE statistics, *DATA analysis software
Abstract

Purpose: To assess the cross-sectional association between dietary indexes (DI) that underlie, respectively, the Nutri-score (NS), the proposed Canadian 'High In' Symbol (CHIL) and the Diabetes Canada Clinical Practice Guidelines (DCCP) with food consumption, nutrient intakes and metabolic markers. Methods: 1836 adults (18–74 years) participating in the representative ESTEBAN study, conducted in mainland France in 2014–2016, were included in the analysis. Food consumption was assessed with three repeated 24 h dietary recalls. Anthropometric measurements and biomarkers of metabolic risk (cholesterol—total, LDL (Low Density Lipoprotein), HDL (High Density Lipoprotein)—triglycerides, glucose) were obtained through a clinical examination and fasting blood draw. The DI were assessed for their association with food consumption, dietary intakes and metabolic biomarkers as quintiles and continuous variables using multi-adjusted linear regression. Heathier diets were assigned to lower scores. Results: Correlations between scores ranged from + 0.62 between CHIL-DI and NS-DI to + 0.75 between NS-DI and DCCP-DI. All DIs discriminated individuals according to the nutritional quality of their diets through food consumption and nutrient intakes (healthier diets were associated with lower intakes of energy, added sugars and saturated fat; and with higher intakes of fiber, vitamins and minerals). NS-DI was associated with blood glucose (adjusted mean in Q1 = 5 vs. Q5 = 5.46 mmol/dl, ptrend = 0.001) and DCCP-DI was associated with BMI (Q1 = 24.8 kg/m2 vs. Q5 = 25.8 kg/m2, ptrend = 0.025), while CHIL showed no significant association with any anthropometric measures or biomarkers. Conclusions: This study provides elements supporting the validity of the nutrient profiling systems underlying front-of-package nutrition labellings (FOPLs) to characterize the healthiness of diets. [ABSTRACT FROM AUTHOR]

Published
2023
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6. Can individual fatty acids be used as functional biomarkers of dairy fat consumption in relation to cardiometabolic health? A narrative review—CORRIGENDUM.

Author

Sellem, Laury, Jackson, Kim G., Paper, Laura, Givens, Ian D., and Lovegrove, Julie A.

Subjects
CARDIOVASCULAR diseases risk factors, BIOMARKERS, DAIRY products, DIETARY fats, FATTY acids
Abstract

A correction is presented to the article "Can individual fatty acids be used as functional biomarkers of dairy fat consumption in relation to cardiometabolic health?"

Published
2022
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7. The interplay between innate lymphoid cells and T cells

Author

Gayetri Ramachandran, Rachel Golub, Marie Cherrier, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Lymphocytes et Immunité - Lymphocytes and Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), M.C. is supported by INSERM and Association François Aupetit dedicated to patients suffering from IBD. R.G. work is supported by Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Université de Paris, and ANR project NASHILCCD8 (#18-CE15-0024-01)., We thank Serge van de Pavert for critical discussions and for review of the paper., ANR-18-CE15-0024,NASHILCCD8,Contribution des ILC et des cellules T CD8 à la stéatose hépatique non alcoolique et à sa progression vers l'hépatocarcinome.(2018), Vougny, Marie-Christine, APPEL À PROJETS GÉNÉRIQUE 2018 - Contribution des ILC et des cellules T CD8 à la stéatose hépatique non alcoolique et à sa progression vers l'hépatocarcinome. - - NASHILCCD82018 - ANR-18-CE15-0024 - AAPG2018 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
0301 basic medicine, Cell type, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Context (language use), Cell Communication, Biology, Gut flora, Adaptive Immunity, Lymphocyte Activation, Substrate Specificity, Immunomodulation, 03 medical and health sciences, 0302 clinical medicine, Immune system, T-Lymphocyte Subsets, Immunology and Allergy, Animals, Humans, skin and connective tissue diseases, Immunity, Cellular, Innate lymphoid cell, Cell Differentiation, Acquired immune system, biology.organism_classification, Immunity, Innate, body regions, 030104 developmental biology, Gene Expression Regulation, Host-Pathogen Interactions, [SDV.IMM]Life Sciences [q-bio]/Immunology, Neuroscience, Immunologic Memory, Function (biology), Homeostasis, Biomarkers, 030215 immunology, Signal Transduction
Abstract

International audience; ILCs and T cells are closely related functionally but they significantly differ in their ability to circulate, expand, and renew. Cooperation and reciprocal functional regulation suggest that these cell types are more complementary than simply redundant during immune responses. How ILCs shape T-cell responses is strongly dependent on the tissue and inflammatory context. Likewise, indirect regulation of ILCs by adaptive immunity is induced by environmental cues such as the gut microbiota. Here, we review shared requirements for the development and function of both cell types and divergences in the orchestration of prototypic immune functions. We discuss the diversity of functional interactions between T cells and ILCs during homeostasis and immune responses. Identifying the location and the nature of the tissue microenvironment in which these interactions are taking place may uncover the remaining mysteries of their close encounters.

Published
2020

8. Advantages and disadvantages of the use of the CSF Amyloid β (Aβ) 42/40 ratio in the diagnosis of Alzheimer’s Disease

Author

Markus Otto, Henrik Zetterberg, Piotr Lewczuk, Oskar Hansson, Sylvain Lehmann, Clinical Memory Research Unit [Malmö, Suède], Department of Clinical Sciences [Malmö, Suède], Lund University [Malmö, Suède]-Lund University [Malmö, Suède], Memory Clinic [Malmö, Suède], Skåne University Hospital [Malmö, Suède], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Neurology [Ulm, Allemagne], Universität Ulm - Ulm University [Ulm, Allemagne], Clinical Neurochemistry Laboratory [Göteborg, Suède], Department of Psychiatry and Neurochemistry [Goteborg], Institute of Neuroscience and Physiology [Göteborg]-Sahlgrenska Academy at University of Gothenburg [Göteborg]-Institute of Neuroscience and Physiology [Göteborg]-Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Neurodegenerative Disease [Londres, Royaume-Uni], Institute of Neurology [London], University College of London [London] (UCL)-University College of London [London] (UCL), UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), Department of Psychiatry and Psychotherapy [Erlangen, Allemagne], Universitätsklinikum Erlangen [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Department of Neurodegeneration Diagnostics [Bialystok, Pologne], Medical University of Bialystok [Bialystok, Pologne], Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Universitätsklinikum Erlangen [Erlangen, Allemagne], Fujirebio Europe sponsored this paper, however, it had no influence on its factual content. PL was supported by the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. OH has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio and Euroimmun. HZ’s research is supported by the Swedish Research Council, the European Research Council, the Knut and Alice Wallenberg Foundation, the Olav Thon Foundation, the UK Dementia Research Institute at UCL and Swedish State Support for Clinical Research (ALFGBG)., Lund University [Lund]-Lund University [Lund], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Medical University of Białystok (MUB), and Bodescot, Myriam

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Neurology, Amyloid β, Cognitive Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Diagnostic accuracy, Disease, Review, Aβ 42/40 ratio, Alzheimer's Disease, lcsh:RC346-429, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Medizinische Fakultät, Alzheimer Disease, Internal medicine, medicine, Dementia, Humans, ddc:610, Alzheimer’s Disease, Cognitive impairment, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biochemical markers, lcsh:Neurology. Diseases of the nervous system, Cerebrospinal Fluid, Amyloid beta-Peptides, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Peptide Fragments, 030104 developmental biology, Aβ42/40 ratio, Neurology (clinical), business, 030217 neurology & neurosurgery, Amyloidβ Peptides, Biomarkers
Abstract

International audience; The cerebrospinal fluid (CSF) biochemical markers (biomarkers) Amyloidβ 42 (Aβ42), total Tau (T-tau) and Tau phosphorylated at threonine 181 (P-tau181) have proven diagnostic accuracy for mild cognitive impairment and dementia due to Alzheimer's Disease (AD). In an effort to improve the accuracy of an AD diagnosis, it is important to be able to distinguish between AD and other types of dementia (non-AD). The concentration ratio of Aβ42 to Aβ40 (Aβ42/40 Ratio) has been suggested to be superior to the concentration of Aβ42 alone when identifying patients with AD. This article reviews the available evidence on the use of the CSF Aβ42/40 ratio in the diagnosis of AD. Based on the body of evidence presented herein, it is the conclusion of the current working group that the CSF Aβ42/40 ratio, rather than the absolute value of CSF Aβ42, should be used when analysing CSF AD biomarkers to improve the percentage of appropriately diagnosed patients.

Published
2019

9. Cellular Senescence: Defining a Path Forward

Author

John M. Sedivy, Paul D. Robbins, Cleo L. Bishop, Vassilis G. Gorgoulis, Konstantinos Vougas, Konstantinos Evangelou, Valery Krizhanovsky, Dorothy C. Bennett, Eiji Hara, Diana Jurk, Gerardo Ferbeyre, Judith Campisi, Masashi Narita, Laura J. Niedernhofer, Manuel Serrano, Clemens A. Schmitt, Peter D. Adams, Oliver Bischof, Andrea Alimonti, Marco Demaria, Jesús Gil, Daohong Zhou, Manuel Collado, Thomas von Zglinicki, Andrea B. Maier, João F. Passos, Institut Pasteur [Paris], National and Kapodistrian University of Athens (NKUA), University of Manchester [Manchester], Biomedical Research Foundation of the Academy of Athens (BRFAA), Institute of Cancer Sciences [Glasgow, UK] (CR-UK Beatson Institute), University of Glasgow, Sanford Burnham Prebys Medical Discovery Institute, Oncology Institute of Southern Switzerland (IOSI), Università della Svizzera italiana = University of Italian Switzerland (USI), Universita degli Studi di Padova, Veneto Institute of Molecular Medicine [Padova, Italy] (VIMM), University of London [London], Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Bart's and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Buck Institute for Research on Aging, Universidade de Santiago de Compostela [Spain] (USC ), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Université de Montréal (UdeM), MRC London Institute of Medical Sciences (LMC), Imperial College London, Research Institute for Microbial Diseases [Osaka, Japan] (RIMD), Osaka University [Osaka], Department of Molecular Cell Biology [Rehovot], Weizmann Institute of Science [Rehovot, Israël], Robert and Arlene Kogod Center on Aging [Rochester, MN, USA], Mayo Clinic, Vrije Universiteit Amsterdam [Amsterdam] (VU), University of Melbourne, University of Cambridge [UK] (CAM), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Kepler University Hospital, Brown University, Newcastle University [Newcastle], University of Florida [Gainesville] (UF), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Institució Catalana de Recerca i Estudis Avançats (ICREA), University of Groningen [Groningen], European Research Institute for the Biology of Ageing [Groningen] (ERIBA), University Medical Center Groningen [Groningen] (UMCG), M.D. is funded by the Dutch Cancer Foundation, Netherlands (grant ID 10989). V.G., K.E., and K.V. were financially supported by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grants agreement no. 722729 (SYNTRAIN), the Welfare Foundation for Social & Cultural Sciences (KIKPE), Greece, the KIKPE Foundation, Athens, Greece, Pentagon Biotechnology, UK, DeepMed IO, UK, grant no. 775 from the Hellenic Foundation for Research and Innovation (HFRI), and NKUA-SARG grants 70/3/9816, 70/3/12128, and 70/3/15603. M.S.: is funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and 'laCaixa' Foundation., We would like to thank Nikolaos Kastrinakis, Panagiotis V.S. Vasileiou, Gkikas Magiorkinis, Eleni Fitsiou, and Michela Borghesan for their valuable support to this work. We apologize in advance that, for reason of space, we have omitted the citations of relevant papers and reviews., National and Kapodistrian University of Athens = University of Athens (NKUA | UoA), Organisation Nucléaire et Oncogenèse - Nuclear Organization and Oncogenesis, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], University of Santiago de Compostela [Spain] (USC), Centre de recherche du Chum [Montréal] (CRCHUM), Université de Montréal [Montréal], Research Institute for Microbial Diseases, Weizmann Institute of Science, University of Minnesota [Twin Cities], Max Delbrück Center for Molecular Medicine [Berlin], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, University of Florida [Gainesville], University of Barcelona, Università degli Studi di Padova = University of Padua (Unipd), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Narita, Masashi [0000-0001-7764-577X], and Apollo - University of Cambridge Repository

Subjects
Senescence, EXPRESSION, Aging, Cell cycle checkpoint, [SDV]Life Sciences [q-bio], Cell, DNA-DAMAGE RESPONSE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mitochondrion, Biology, General Biochemistry, Genetics and Molecular Biology, CHROMATIN LANDSCAPE, 03 medical and health sciences, 0302 clinical medicine, MITOCHONDRIA, ONCOGENE-INDUCED SENESCENCE, medicine, Humans, OXIDATIVE STRESS, Senolytic, Cellular Senescence, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, P53, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Genetic Diseases, Inborn, DARK SIDE, Cell Cycle Checkpoints, 06 Biological Sciences, CANCER, Chromatin, medicine.anatomical_structure, Gene Expression Regulation, CELLS, Developmental biology, 030217 neurology & neurosurgery, Biomarkers, Developmental Biology
Abstract

International audience; Cellular senescence is a cell state implicated in various physiological processes and a wide spectrum of age-related diseases. Recently, interest in therapeutically targeting senescence to improve healthy aging and age-related disease, otherwise known as senotherapy, has been growing rapidly. Thus, the accurate detection of senescent cells, especially in vivo, is essential. Here, we present a consensus from the International Cell Senescence Association (ICSA), defining and discussing key cellular and molecular features of senescence and offering recommendations on how to use them as biomarkers. We also present a resource tool to facilitate the identification of genes linked with senescence, SeneQuest (available at http://Senequest.net). Lastly, we propose an algorithm to accurately assess and quantify senescence, both in cultured cells and in vivo.

Published
2019
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10. Optimization of a magnetic bead-based assay (MAGPIX®-Luminex) for immune surveillance of exposure to malaria using multiple Plasmodium antigens and sera from different endemic settings

Author

Aissata Basse, Inès Vigan-Womas, Alioune Dieye, Cheikh Loucoubar, Babacar Mbengue, Marie Louise Varela, Ronald Perraut, Aissatou Touré, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Madagascar, Département Parasites et Insectes vecteurs - Department of Parasites and Insect Vectors, Institut Pasteur [Paris], This study was supported by grants from Institut Pasteur Fondation, from Rotary International, ACIP (Institut Pasteur, N°25_2012) and EDCTP—European & Developing Countries Clinical Trials Partnership., We thank Dr Odile Mercereau-Puijalon and Dr Shirley Longacre for constant support and providing antigens, we are grateful to Dr Shirley Longacre for revising this paper. We thank Drs Marc Jouan and Jérôme Salomon from Division International (Institut Pasteur, Paris) for their help to initiate this work in the very early steps. We are grateful to the villagers of Dielmo and Ndiop for their active participation and continuing collaboration in the project and Pr Bacary Diatta for help providing hospital samples., and Institut Pasteur [Paris] (IP)

Subjects
0301 basic medicine, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium falciparum, Protozoan Proteins, Antigens, Protozoan, Plasmodium malariae, Biology, lcsh:Infectious and parasitic diseases, Serology, 03 medical and health sciences, 0302 clinical medicine, Antigen, parasitic diseases, medicine, lcsh:RC109-216, Multiplex, Malaria, Falciparum, IgG response, Immunoassay, medicine.diagnostic_test, Immunomagnetic Separation, Magnetic beads assay, Methodology, medicine.disease, biology.organism_classification, 3. Good health, Malaria, 030104 developmental biology, Infectious Diseases, Immunology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Parasitology, Antibody, Biomarkers
Abstract

International audience; Background: Serological markers are potentially useful tools for monitoring the progress of malaria control programs , but a better understanding of antibody response dynamics is necessary. The use of a magnetic bead-based immunoassay (MBA) is advantageous compared to ELISA, due to its multiplexing capacity, but limited information is available on the standardization and validation of this assay. Methods: Several parameters for multiplex testing of antibodies to Plasmodium antigens were analysed using a set of 4 antigens and 98 sera from Senegalese rural asymptomatic and urban symptomatic individuals. The 4 antigens included Plasmodium falciparum CSP and PfAMA1 peptides, recombinant P. falciparum MSP4p20 and a Plasmodium malariae CSP (PmCSP) peptide. Comparisons with ELISA were done using MSP4p20 and whole schizont extract (SE) antigens.Results: The use of fewer beads (1000 beads per well instead of 2000) and 5 µg of antigen per 10 6 bead were validated as lower amounts. The use of a carrier protein (BSA) was shown to be critical when using peptides and the effect of a 24 h delayed measures was evaluated (5-25% signal decrease). Analysis of Ab responses showed almost equally high levels and prevalence in all transmission settings. Clear distinctions between rural and urban malaria were noted using PmCSP and SE antigens.Conclusions: This study underlines the importance of further optimization of the MBA technique and highlights the interest of using multistage/multispecies antigens for surveillance of malaria in endemic settings.

Published
2018

11. Standardized whole blood stimulation improves immunomonitoring of induced immune responses in multi-center study

Author

Alain Savenay, Matthew L. Albert, Delphine Louis, Manfred Schmolz, Nina Salabert-Le Guen, Olivier Lantz, Régis Josien, Darragh Duffy, Françoise Mascart, Antoine Toubert, Marie Noelle Ungeheuer, Vincent Rouilly, Raouf Djebali, Lydia Redjah, José J.G. Ruiz de Morales, Catherine Ottone, Véronique Corbière, Eva Martínez-Cáceres, Cécile Braudeau, Samuel S.T. LaBrie, Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle (CRT), Institut Pasteur [Paris], Laboratoire d’Immunologie, Centre d’Immunomonitorage Nantes Atlantique (CIMNA), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), laboratoire de vaccinologie et immunité mucosale, Université Libre de Bruxelles [Bruxelles] (ULB), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Myriad RBM, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital Universitari Germans Trias I Pujol, Immunobiology Clinic, Hôpital Erasme, Complejo Asistencial Universitario de León, Alloimmunité-Autoimmunité-Transplantation (A2T), 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), HOT Screen GmbH, Genentech, Inc. [San Francisco], TruCulture tubes, stimuli, and protein Luminex XMAP analysis were provided by Myriad RBM, Inc (Austin, USA) and TruCulture tubes were manufactured at HOT Screen (Reutlingen, Germany). Donor recruitment costs were covered by each participating FOCIS center of excellence. Author contributions: DD, VR, VC, SL, OL, EMC, RP, MS, AT & MLA designed the study. CB, RD, MNU, DL, FM, JGRM, CO, LR, AS performed experiments. DD, VR, & MLA performed analysis and wrote the paper. All authors reviewed the manuscript., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Université libre de Bruxelles (ULB), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche Translationnelle ( CRT ), Centre Hospitalier Universitaire de Nantes, Centre de Recherche en Transplantation et Immunologie ( U1064 Inserm - CRTI - CHU Nantes ), Université de Nantes ( UN ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université Libre de Bruxelles [Bruxelles] ( ULB ), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources ( ICAReB ), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Curie, Alloimmunité-Autoimmunité-Transplantation ( A2T ), and Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
0301 basic medicine, Lipopolysaccharides, Whole blood stimulation, CD3 Complex, medicine.medical_treatment, CD8 Antigens, Point-of-Care Systems, Immunology, Stimulation, Blood Donors, Immunologic Tests, Peripheral blood mononuclear cell, Antibodies, Functional immune responses, 03 medical and health sciences, Immune system, medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Humans, Whole blood, biology, business.industry, Immunotherapy, Multi-center clinical studies, 3. Good health, Vaccination, Immunomonitoring, 030104 developmental biology, Gene Expression Regulation, PBMCs, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, Antibody, business, Biomarkers
Abstract

Functional immune responses are increasingly important for clinical studies, providing in depth biomarker information to assess immunotherapy or vaccination. Incorporating functional immune assays into routine clinical practice has remained limited due to challenges in standardizing sample preparation. We recently described the use of a whole blood syringe-based system, TruCulture (R), which permits point-of-care standardized immune stimulation. Here, we report on a multi-center clinical study in seven FOCIS Centers of Excellence to directly compare TruCulture to conventional PBMC methods. Whole blood and PBMC5 from healthy donors were exposed to LPS, anti-CD3 anti-CD28 antibodies, or media alone. 55 protein analytes were analyzed centrally by Luminex multi-analyte profiling in a CLIA-certified laboratory. TruCulture responses showed greater reproducibility and improved the statistical power for monitoring differential immune response activation. The use of TruCulture addresses a major unmet need through a robust and flexible method for immunomonitoring that can be reproducibly applied in multi-center clinical studies. One sentence summary: A multi-center study revealed greater reproducibility from whole blood stimulation systems as compared to PBMC stimulation for studying induced immune responses. (C) 2017 Published by Elsevier Inc.

Published
2017