35 results on '"Tiers, L"'
Search Results
2. RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma
- Author
-
Viziteu, E, Klein, B, Basbous, J, Lin, Y-L, Hirtz, C, Gourzones, C, Tiers, L, Bruyer, A, Vincent, L, Grandmougin, C, Seckinger, A, Goldschmidt, H, Constantinou, A, Pasero, P, Hose, D, and Moreaux, J
- Published
- 2017
- Full Text
- View/download PDF
3. Tau protein in cerebrospinal fluid: a novel biomarker of the time of death?
- Author
-
Peyron, PA, Hirtz, C, Baccino, E, Ginestet, N, Tiers, L, Martinez, AY, Lehmann, S, and Delaby, C
- Subjects
Cerebrospinal fluid ,Phosphorylated tau ,Post-mortem interval ,Tau protein ,Biochemistry ,Forensic pathology - Abstract
Background Tau proteins are recognized biomarkers of neurodegeneration and neuronal damage in the cerebrospinal fluid (CSF). It has also been suggested that these CSF proteins could increase post-mortem due to neuronal death. The aim of this study was to investigate the changes in CSF total and phosphorylated tau (p-tau) levels in the early post-mortem interval (PMI), to determine whether these proteins could be relevant biomarkers of time since death. Methods Tau and p-tau levels were measured by ELISA in lumbar and cisternal CSF samples from 82 corpses (46 men, 36 women, mean age: 72.4 +/- 15.2 years) with a PMI < 12 h. Forty-eight of them were considered neurologically healthy at the time of death. Rectal and tympanic temperatures were also measured in 37 individuals, and two validated temperature-based methods of PMI estimation were applied (Henssge's nomogram and Baccino's method). Results CSF tau and p-tau levels were significantly increased, with respective median values of 3315 pg/mL and 68.5 pg/mL in the whole cohort, while lower but still increased levels were observed in neurologically healthy patients. Sub-occipital punctures systematically provided higher tau and p-tau values (p < 0.0001). Despite a great inter-individual variability, the concentrations of both biomarkers were positively correlated with the early PMI, with the highest correlation for cisternal p-tau (r = 0.50, p < 0.0001 in the whole cohort; r = 0.58, p = 0.0003 in the neurologically healthy patients). Higher levels of CSF biomarkers were observed for PMI > 6 h versus PMI 6 h), with a Se of 83% and a Sp of 100% (AUC = 0.95). Conclusion Our findings suggest that CSF tau and p-tau proteins could serve as potential biomarkers of time since death, in association with tympanic temperature. The practical applicability of such an integrated approach has to be assessed by further studies.
- Published
- 2021
4. Cytokines as new biomarkers of skin wound vitality
- Author
-
Peyron, PA, Colomb, S, Becas, D, Adriansen, A, Gauchotte, G, Tiers, L, Marin, G, Lehmann, S, Baccino, E, Delaby, C, and Hirtz, C
- Subjects
Immunoassay ,integumentary system ,Wound ,Cytokines ,Vitality ,Immunohistochemistry ,Forensic pathology - Abstract
Background The diagnosis of skin wound vitality is currently based on standard histology, but histological findings lack sensitivity in case of a short survival time. New reliable biomarkers of vitality are therefore strongly needed. We assessed the ability of 10 candidate cytokines (IFN-gamma, IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-alpha) to discriminate between vital and early post-mortem wounds. Methods Twenty-four cadavers with a recent open skin wound (< 3 h) were included (20 men, 4 women, mean age = 51.0 +/- 24.3 years). An early post-mortem wound was performed in an uninjured skin area, and both wounds were sampled at the autopsy (post-mortem interval (PMI) = 66.3 +/- 28.3 h). Needle-puncture sites related to resuscitation cares were included as very early post-mortem wounds (n = 6). In addition to standard histology, cytokines levels were simultaneously measured in each sample using a multiplex sandwich immunoassay, then normalized on healthy skin levels. A quantitative evaluation of IL-8-positive cells in ante- and post-mortem wound samples was also performed. Results In the training set of samples (n = 72), cytokine levels were significantly higher in vital wounds (mean age = 47 +/- 53 min) than in post-mortem wounds (mean PMI = 6.9 +/- 9.0 h) (p < 0.2), except for two cytokines (IFN-gamma and IL-2). IL-8 was the best discriminatory cytokine (Se = 54%, Sp = 100%, AUC = 0.79), while a multivariate model combining IL-4 and IL12p70 was a bit more discriminant (Se = 55%, Sp = 100%, AUC = 0.84). In the validation set (n = 72), the discriminatory power of the cytokines and the predictive model was slightly lower, with IL-8 remaining the best cytokine (Se = 46%, Sp = 96%, AUC = 0.75). The predictive model remained highly specific (Sp = 100%). Both the cytokines and the predictive model allowed the iatrogenic injuries to be correctly classified as post-mortem wounds. Standard histology and immunohistochemistry showed 21% sensitivity and a specificity of 79% and 100%, respectively. Only two iatrogenic wounds could be properly categorized histologically. Conclusion This study suggests that cytokines could be useful biomarkers of skin wound vitality and that the immunoassay method could be more sensitive than immunohistochemistry to identify wounds with a short survival time. Further research is underway to confirm these preliminary data.
- Published
- 2021
5. Proteomics of primary mesenchymal stem cells
- Author
-
Roche, S, Provansal, M, Tiers, L, Jorgensen, C, and Lehmann, S
- Published
- 2006
- Full Text
- View/download PDF
6. Strain effect on extracellular laccase activities fromBotrytis cinerea
- Author
-
Quijada-Morin, N., primary, Garcia, F., additional, Lambert, K., additional, Walker, A.-S., additional, Tiers, L., additional, Viaud, M., additional, Sauvage, F.-X., additional, Hirtz, C., additional, and Saucier, C., additional
- Published
- 2017
- Full Text
- View/download PDF
7. Strain effect on extracellular laccase activities from <italic>Botrytis cinerea</italic>.
- Author
-
Quijada‐Morin, N., Garcia, F., Lambert, K., Walker, A.‐S., Tiers, L., Viaud, M., Sauvage, F.‐X., Hirtz, C., and Saucier, C.
- Subjects
LACCASE ,BOTRYTIS cinerea ,EXTRACELLULAR enzymes ,FUNGAL enzymes ,OXIDATION of phenols ,GLYCOSYLATION - Abstract
Abstract: Background and Aims: Laccase enzymes produced by
Botrytis cinerea are involved in the oxidation of phenolic substances during the development of grey mould, which causes significant economic losses. The aim of this work was to study the structural and activity characteristics of the laccase enzymes secreted by three B. cinerea strains that are involved in the development of grey mould. Methods and Results: Laccase enzymes obtained from three B. cinerea strains [one reference strain (B05.10) and two strains obtained from two French vineyards (VA612 and RM344)] were characterised. Analysis by LC‐QTOF‐MS revealed that the three strains contained a mixture of Laccase‐2‐BcLCC2 and Laccase‐3‐BcLCC7. The structural characteristics of the laccases from the three strains, such as molecular weight and glycosylation degree, were identical. Nevertheless, their catalytic activities were significantly different. Conclusions: Differences in catalytic activities could be due either to possible differences in the relative amount of Laccase‐2‐BcLCC2 and Laccase‐3‐BcLCC7 produced by each strain or to differences in the glycosidic fraction of the enzymes. Significance of the Study: The severity of the infection caused by B. cinerea may be not only related to the infection level but also to the strain involved. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
8. Apport de la tomographie par émission monophotonique de perfusion dans le diagnostic étiologique des démences : Confrontations cliniques, tomographiques et neuropathologiques
- Author
-
Lehmann, S, Gabelle, A, Roche, Stéphane, Thouvenot, E, Peoc'h, K, Laplanche, J, Tiers, L, Geny, C, Touchon, J, Plateforme de Protéomique Clinique, and CHU Saint-Eloi
- Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] - Abstract
International audience; Introduction : Le diagnostic positif des affections neurodégénératives et en particulier de la maladie d’Alzheimer (MA)devient une exigence pour la prise en charge des patients et pour l’évaluation des nouvelles molécules “ anti-démence ”.Actuellement, le diagnostic de MA combine de données anamnestiques, cliniques, neuropsychologiques, d’imageriemorphologique ou fonctionnelle, et récemment des biomarqueurs dans le liquide céphalo-rachidien. Les données surles marqueurs plasmatiques, en particulier l’Abeta restent décevantes.L’objectif principal de notre étude est d’identifier de nouvelles protéines plasmatiques ou sériques par technique de protéomique permettant d’optimiser le diagnostic positif de la MA. Matériel/méthode : 70 prélèvements de patients atteints de troubles cognitifs sont analysés par protéomique différentielle de type SELDI (“ Surface enhanced laser desorption/ionization time-of-flight mass spectrometry ”). Ce système de “ puces à protéine ” (Bio-Rad) permet de capturer des protéines sur différentes surfaces chromatographiques et de les détecter en spectrométrie de masse. Trois groupes de patients sont comparés : 1/ MA, 2/ démence non MA, 3/ affection neurologique sans atteinte cognitive. Ce protocole est validé par le comité d’éthique, le CPP et la CNIL. Résultats : La première partie du travail a permis de valider une méthode de préfractionnement des prélèvements permettant d’optimiser la détection des marqueurs protéiques de faible concentration. La détection protéique par SELDI a permis de sélectionner de nouveaux marqueurs potentiels permettant de différencier le groupe MA des autres démences. Certains sont en cours d’identification en spectrométrie de masse. Conclusion : La recherche de biomarqueurs sanguins représente un enjeu majeur dans le cadre du diagnostic positif de la MA. L’intérêt clinique et la pertinence physiopathologique des biomarqueurs potentiels sélectionnés dans notre étude semblent des plus prometteurs.
- Published
- 2009
9. Proteomic analysis of mare follicular fluid
- Author
-
Nadaf, Somayyeh, Roche, S., Tiers, L., Lehmann, S., Gérard, Nadine, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and ProdInra, Migration
- Subjects
[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,[INFO]Computer Science [cs] ,[INFO] Computer Science [cs] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2009
10. Comparison of different immunoaffinity columns to remove high abundant proteins from follicular fluid of different species
- Author
-
Nadaf, S., Roche, S., Tiers, L., Lehmann, S., Gérard, Nadine, ProdInra, Migration, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Plateforme de Protéomique Clinique, CHU Saint-Eloi, and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,[INFO]Computer Science [cs] ,[INFO] Computer Science [cs] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2008
11. Transcriptomic and proteomic analyses of human endometrial receptivity under natural cycle
- Author
-
Haouzi, D., primary, Hirtz, C., additional, Dechaud, H., additional, Tiers, L., additional, Lehmann, S., additional, and Hamamah, S., additional
- Published
- 2012
- Full Text
- View/download PDF
12. ENDOMETRIOSIS, ENDOMETRIUM, IMPLANTATION AND FALLOPIAN TUBE
- Author
-
Nesbitt-Hawes, E., primary, Campbell, N., additional, Won, H., additional, Maley, P., additional, Henry, A., additional, Abbott, J., additional, Potdar, N., additional, Mason-Birks, S., additional, Elson, C. J., additional, Gelbaya, T. A., additional, Nardo, L. G., additional, Stavroulis, A., additional, Nnoaham, K., additional, Hummelshoj, L., additional, Zondervan, K., additional, Saridogan, E., additional, GSWH Consortium, W. E. R. F., additional, Chamie, L. P., additional, Soares, A. C. P., additional, Kimati, C. T., additional, Gomes, C., additional, Fettback, P., additional, Riboldi, M., additional, Serafini, P., additional, Lalitkumar, S., additional, Menezes, J., additional, Evdokia, D., additional, Gemzell-Danielsson, K., additional, Lalitkumar, P. G. L., additional, Bailey, J., additional, Newman, T. A., additional, Johnston, A., additional, Zisimopoulou, K., additional, White, M., additional, Sadek, K., additional, Shreeve, N., additional, Macklon, N., additional, Cheong, Y., additional, Al-Akoum, M., additional, Akoum, A., additional, Giles, J., additional, Garrido, N., additional, Vidal, C., additional, Mondion, M., additional, Gallo, C., additional, Ramirez, J., additional, Pellicer, A., additional, Remohi, J., additional, Ghosh, S., additional, Chattopadhyay, R., additional, Jana, S., additional, Goswami, S. K., additional, Bose, G., additional, Chakravarty, M., additional, Chowdhuri, K., additional, Chakravarty, B. N., additional, Kendirci Ceviren, A., additional, Ozcelik Tanriverdi, N., additional, Urfan, A., additional, Donmez, L., additional, Isikoglu, M., additional, Romano, A., additional, Schreinemacher, M. H., additional, Backes, W. H., additional, Slenter, J. M., additional, Xanthoulea, S. A., additional, Delvoux, B., additional, van Winden, L., additional, Beets-Tan, R. G., additional, Evers, J. L. H., additional, Dunselman, G. A. J., additional, Jana, S. K., additional, Chaudhury, K., additional, Maruyama, T., additional, Yamasaki, A., additional, Miyazaki, K., additional, Arase, T., additional, Uchida, H., additional, Yoshimura, Y., additional, Kaser, D., additional, Ginsburg, E., additional, Missmer, S., additional, Correia, K., additional, Racowsky, C., additional, Streuli, I., additional, Chouzenoux, S., additional, de Ziegler, D., additional, Chereau, C., additional, Weill, B., additional, Chapron, C., additional, Batteux, F., additional, Arianmanesh, M., additional, Fowler, P. A., additional, Al-Gubory, K. H., additional, Urata, Y., additional, Osuga, Y., additional, Izumi, G., additional, Nagai, M., additional, Takamura, M., additional, Yamamoto, N., additional, Saito, A., additional, Hasegawa, A., additional, Takemura, Y., additional, Harada, M., additional, Hirata, T., additional, Hirota, Y., additional, Yoshino, O., additional, Koga, K., additional, Taketani, Y., additional, Mohebbi, A., additional, Janan, A., additional, Nasri, S., additional, Lakpour, M. R., additional, Ramazanali, F., additional, Moini, A., additional, Aflatoonian, R., additional, Germeyer, A., additional, Novak, O., additional, Renke, T., additional, Jung, M., additional, Jackus, J., additional, Toth, B., additional, Strowitzki, T., additional, Bhattacharya, J., additional, Mitra, A., additional, Kundu, S., additional, Pal, M., additional, Kundu, A., additional, Gumusel, A., additional, Basar, M., additional, Yaprak, E., additional, Aslan, E., additional, Arda, O., additional, Ilvan, S., additional, Kayisli, U., additional, Guzel, E., additional, Haouzi, D., additional, Monzo, C., additional, Lehmann, S., additional, Hirtz, C., additional, Tiers, L., additional, Hamamah, S., additional, Choi, D., additional, Choi, J., additional, Jo, M., additional, Lee, E., additional, Shen, X., additional, Wang, B. I. N., additional, Li, X., additional, Tamura, I., additional, Maekawa, R., additional, Asada, H., additional, Tamura, H., additional, Sugino, N., additional, Liu, H., additional, Jiang, Y., additional, Chen, J., additional, Zhu, L., additional, Wang, B., additional, Yan, G., additional, Sun, H., additional, Coughlan, C., additional, Sinagra, M., additional, Ledger, W., additional, Li, T. C., additional, Laird, S. M., additional, Dafopoulos, K., additional, Vrekoussis, T., additional, Chalvatzas, N., additional, Messini, C. I., additional, Kalantaridou, S., additional, Georgoulias, P., additional, Messinis, I. E., additional, Makrigiannakis, A., additional, Xue, Q., additional, Xu, Y., additional, Zuo, W. L., additional, Zhang, L., additional, Shang, J., additional, Zhu, S. N., additional, Bulun, S. E., additional, Tomassetti, C., additional, Geysenbergh, B., additional, Meuleman, C., additional, Fieuws, S., additional, D'Hooghe, T., additional, Suginami, K., additional, Sato, Y., additional, Horie, A., additional, Matsumoto, H., additional, Fujiwara, H., additional, Konishi, I., additional, Jung, Y., additional, Cho, S., additional, Choi, Y., additional, Lee, B., additional, Seo, S., additional, Urman, B., additional, Yakin, K., additional, Oktem, O., additional, Alper, E., additional, Taskiran, C., additional, Aksoy, S., additional, Takeuchi, K., additional, Kurematsu, T., additional, Yu-ki, Y., additional, Fukumoto, Y., additional, Homan, Y., additional, Sata, Y., additional, Kuroki, Y., additional, Takeuchi, M., additional, Awata, S., additional, Muneyyirci-Delale, O., additional, Charles, C., additional, Anopa, J., additional, Osei-Tutu, N., additional, Dalloul, M., additional, Weedon, J., additional, Muney, A., additional, Stratton, P., additional, Yilmaz, B., additional, Kilic, S., additional, Aksakal, O., additional, Kelekci, S., additional, Aksoy, Y., additional, Lordlar, N., additional, Sut, N., additional, Gungor, T., additional, Chan, J., additional, Tan, C. W., additional, Lee, Y. H., additional, Tan, H. H., additional, Choolani, M., additional, Griffith, L., additional, Oldeweme, J., additional, Barcena de Arellano, M. L., additional, Reichelt, U., additional, Schneider, A., additional, Mechsner, S., additional, Munch, S., additional, Vercellino, G. F., additional, Chiantera, V., additional, Santoro, L., additional, D'Onofrio, F., additional, Campo, S., additional, Ferraro, P. M., additional, Tondi, P., additional, Gasbarrini, A., additional, Santoliquido, A., additional, Jung, M. H., additional, Kim, H. Y., additional, Arnold, J., additional, Buttner, A., additional, Karaer, A., additional, Celik, O., additional, Bay Karabulut, A., additional, Celik, E., additional, Kiran, T. R., additional, Simsek, O. Y., additional, Yilmaz, E., additional, Turkcuoglu, I., additional, Tanrikut, E., additional, Alieva, K., additional, Kulakova, E., additional, Ipatova, M., additional, Smolnikova, V., additional, and Kalinina, E., additional
- Published
- 2012
- Full Text
- View/download PDF
13. P2a-11 Apport de la tomographie par émission monophotonique de perfusion dans le diagnostic étiologique des démences : Confrontations cliniques, tomographiques et neuropathologiques
- Author
-
Lehmann, S., primary, Gabelle, A., additional, Roche, S., additional, Thouvenot, E., additional, Peoc’H, K., additional, Laplanche, J., additional, Tiers, L., additional, Geny, C., additional, and Touchon, J., additional
- Published
- 2009
- Full Text
- View/download PDF
14. 026 Effet de l’interleukine-8 (IL-8) sur les réponses des cellules épithéliales bronchiques humaines
- Author
-
Gras, D., primary, Bonnans, C., additional, Vachier, I., additional, Tiers, L., additional, Godard, P., additional, Lehmann, S., additional, and Chanez, P., additional
- Published
- 2006
- Full Text
- View/download PDF
15. Decreased sA[beta]PP[beta], A[beta]38, and A[beta]40 Cerebrospinal Fluid Levels in Frontotemporal Dementia.
- Author
-
Gabelle A, Roche S, Gény C, Bennys K, Labauge P, Tholance Y, Quadrio I, Tiers L, Gor B, Boulanghien J, Chaulet C, Vighetto A, Croisile B, Krolak-Salmon P, Perret-Liaudet A, Touchon J, and Lehmann S
- Published
- 2011
16. Ultrasensitive digital immunoassays for SOD1 conformation in amyotrophic lateral sclerosis.
- Author
-
Morichon L, Hirtz C, Tiers L, Mezghrani A, Raoul C, Esselin F, La Cruz E, Julien JP, Camu W, and Lehmann S
- Subjects
- Humans, Superoxide Dismutase-1, Biological Assay, Immunoassay, Molecular Conformation, Amyotrophic Lateral Sclerosis
- Abstract
Aim: The aim of this study was to detect misfolded Cu/Zn SOD1 as a potential biomarker for amyotrophic lateral sclerosis (ALS). Materials & methods: Two ultrasensitive immunodetection assays were developed for the quantification of total and misfolded SOD1. Results: The detection of total and misfolded SOD1 was possible in human serum and cerebrospinal fluid. Total SOD1 was increased in cerebrospinal fluid from ALS patients. Misfolded SOD1 had low and variable expression in both control and ALS patient samples. Conclusion: These assays hold promise for improving our understanding of ALS and its detection, and could lead to more effective treatment options in the future. Further studies in larger cohorts are now required.
- Published
- 2023
- Full Text
- View/download PDF
17. Comparison of ultrasensitive and mass spectrometry quantification of blood-based amyloid biomarkers for Alzheimer's disease diagnosis in a memory clinic cohort.
- Author
-
Hirtz C, Busto GU, Bennys K, Kindermans J, Navucet S, Tiers L, Lista S, Vialaret J, Gutierrez LA, Dauvilliers Y, Berr C, Lehmann S, and Gabelle A
- Subjects
- Humans, Proteomics, tau Proteins cerebrospinal fluid, Amyloid beta-Peptides cerebrospinal fluid, Biomarkers cerebrospinal fluid, Amyloid, Peptide Fragments cerebrospinal fluid, Alzheimer Disease pathology
- Abstract
Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder with β-amyloid pathology as a key underlying process. The relevance of cerebrospinal fluid (CSF) and brain imaging biomarkers is validated in clinical practice for early diagnosis. Yet, their cost and perceived invasiveness are a limitation for large-scale implementation. Based on positive amyloid profiles, blood-based biomarkers should allow to detect people at risk for AD and to monitor patients under therapeutics strategies. Thanks to the recent development of innovative proteomic tools, the sensibility and specificity of blood biomarkers have been considerably improved. However, their diagnosis and prognosis relevance for daily clinical practice is still incomplete., Methods: The Plasmaboost study included 184 participants from the Montpellier's hospital NeuroCognition Biobank with AD (n = 73), mild cognitive impairments (MCI) (n = 32), subjective cognitive impairments (SCI) (n = 12), other neurodegenerative diseases (NDD) (n = 31), and other neurological disorders (OND) (n = 36). Dosage of β-amyloid biomarkers was performed on plasma samples using immunoprecipitation-mass spectrometry (IPMS) developed by Shimadzu (IPMS-Shim Aβ
42 , Aβ40 , APP669-711 ) and Simoa Human Neurology 3-PLEX A assay (Aβ42 , Aβ40 , t-tau). Links between those biomarkers and demographical and clinical data and CSF AD biomarkers were investigated. Performances of the two technologies to discriminate clinically or biologically based (using the AT(N) framework) diagnosis of AD were compared using receiver operating characteristic (ROC) analyses., Results: The amyloid IPMS-Shim composite biomarker (combining APP669-711 /Aβ42 and Aβ40 /Aβ42 ratios) discriminated AD from SCI (AUC: 0.91), OND (0.89), and NDD (0.81). The IPMS-Shim Aβ42/40 ratio also discriminated AD from MCI (0.78). IPMS-Shim biomarkers have similar relevance to discriminate between amyloid-positive and amyloid-negative individuals (0.73 and 0.76 respectively) and A-T-N-/A+T+N+ profiles (0.83 and 0.85). Performances of the Simoa 3-PLEX Aβ42/40 ratio were more modest. Pilot longitudinal analysis on the progression of plasma biomarkers indicates that IPMS-Shim can detect the decrease in plasma Aβ42 that is specific to AD patients., Conclusions: Our study confirms the potential usefulness of amyloid plasma biomarkers, especially the IPMS-Shim technology, as a screening tool for early AD patients., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
18. Repeated neurofilament light chain measurements did not capture Riluzole therapeutic effect in amyotrophic lateral sclerosis patients.
- Author
-
Esselin F, De la Cruz E, Hirtz C, Tiers L, Alphandery S, Baudesson L, Taieb G, Camu W, and Lehmann S
- Subjects
- Biomarkers, Female, Humans, Intermediate Filaments, Neurofilament Proteins, Prognosis, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis drug therapy, Riluzole therapeutic use
- Abstract
Background: Little is known about the influence of Riluzole on serum neurofilament light chain (sNfL) levels, a biomarker of prognosis in amyotrophic lateral sclerosis (ALS), and variations with time of sNfL concentrations are controversial., Methods: Sera from ALS patients (n = 141) and controls (n = 33) were collected at inclusion (sNfL1) and second visit (sNfL2, mean delay 10.4 ± 8.7 months). sNfL levels, determined by single-molecule array, were compared between ALS and controls at both time points. sNfL concentration changes were compared between patients with Riluzole (w/Ril) at inclusion in the study and those who were treated by Riluzole following inclusion (w/o Ril). The factors influencing sNfL concentrations and changes were studied using linear regression and multivariate analysis., Results: sNfL levels were higher in ALS patients than in controls at the two time points (p < 0.00001). In ALS patients, sNfL concentrations were higher in females for both sNfL1 (p = 0.014) and sNfL2 (p < 0.001). In the whole ALS group, sNfL levels were higher at sNfL2 than at sNfL1 (p < 0.001). sNfL1 and sNfL2 concentrations were similar between the two ALS subgroups (w/ and w/o Ril). ALS functional rating scale-revised rate of decline and gender were the two main factors significantly influencing both sNfL1 and sNfL2 levels (p < 0.01). However, only gender was shown to significantly influence sNfL changes with time (p = 0.003)., Conclusions: In this study, sNfL levels increased with time in ALS patients and there was no difference between subjects already treated by Riluzole and those treated after sNfL1. Further studies with larger population samples and different sampling intervals are warranted to better determine the real potential of sNfL measurement as a tool to monitor treatment response in ALS., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
19. Deciphering Black Extrinsic Tooth Stain Composition in Children Using Metaproteomics.
- Author
-
Hirtz C, Mannaa AM, Moulis E, Pible O, O'Flynn R, Armengaud J, Jouffret V, Lemaistre C, Dominici G, Martinez AY, Dunyach-Remy C, Tiers L, Lavigne JP, Tramini P, Goldsmith MC, Lehmann S, Deville de Périère D, and Vialaret J
- Abstract
The present study focuses on the use of a metaproteomic approach to analyze Black Extrinsic Tooth Stains, a specific type of pigmented extrinsic substance. Metaproteomics is a powerful emerging technology that successfully enabled human protein and bacterial identification of this specific dental biofilm using high-resolution tandem mass spectrometry. A total of 1600 bacterial proteins were identified in black stain (BS) samples and 2058 proteins in dental plaque (DP) samples, whereas 607 and 582 human proteins were identified in BS and DP samples, respectively. A large diversity of bacteria genera (142) in BS and DP was identified, showing a high prevalence of Rothia, Kingella, Neisseria, and Pseudopropionibacterium in black stain samples. In this work, the high diversity of the dental microbiota and its proteome is highlighted, including significant differences between black stain and dental plaque samples., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)
- Published
- 2022
- Full Text
- View/download PDF
20. Cytokines as new biomarkers of skin wound vitality.
- Author
-
Peyron PA, Colomb S, Becas D, Adriansen A, Gauchotte G, Tiers L, Marin G, Lehmann S, Baccino E, Delaby C, and Hirtz C
- Subjects
- Adult, Aged, Autopsy, Biomarkers, Female, Humans, Immunoassay, Male, Middle Aged, Predictive Value of Tests, Reproducibility of Results, Cytokines, Skin injuries, Wound Healing
- Abstract
Background: The diagnosis of skin wound vitality is currently based on standard histology, but histological findings lack sensitivity in case of a short survival time. New reliable biomarkers of vitality are therefore strongly needed. We assessed the ability of 10 candidate cytokines (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α) to discriminate between vital and early post-mortem wounds., Methods: Twenty-four cadavers with a recent open skin wound (< 3 h) were included (20 men, 4 women, mean age = 51.0 ± 24.3 years). An early post-mortem wound was performed in an uninjured skin area, and both wounds were sampled at the autopsy (post-mortem interval (PMI) = 66.3 ± 28.3 h). Needle-puncture sites related to resuscitation cares were included as very early post-mortem wounds (n = 6). In addition to standard histology, cytokines levels were simultaneously measured in each sample using a multiplex sandwich immunoassay, then normalized on healthy skin levels. A quantitative evaluation of IL-8-positive cells in ante- and post-mortem wound samples was also performed., Results: In the training set of samples (n = 72), cytokine levels were significantly higher in vital wounds (mean age = 47 ± 53 min) than in post-mortem wounds (mean PMI = 6.9 ± 9.0 h) (p < 0.2), except for two cytokines (IFN-γ and IL-2). IL-8 was the best discriminatory cytokine (Se = 54%, Sp = 100%, AUC = 0.79), while a multivariate model combining IL-4 and IL12p70 was a bit more discriminant (Se = 55%, Sp = 100%, AUC = 0.84). In the validation set (n = 72), the discriminatory power of the cytokines and the predictive model was slightly lower, with IL-8 remaining the best cytokine (Se = 46%, Sp = 96%, AUC = 0.75). The predictive model remained highly specific (Sp = 100%). Both the cytokines and the predictive model allowed the iatrogenic injuries to be correctly classified as post-mortem wounds. Standard histology and immunohistochemistry showed 21% sensitivity and a specificity of 79% and 100%, respectively. Only two iatrogenic wounds could be properly categorized histologically., Conclusion: This study suggests that cytokines could be useful biomarkers of skin wound vitality and that the immunoassay method could be more sensitive than immunohistochemistry to identify wounds with a short survival time. Further research is underway to confirm these preliminary data., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2021
- Full Text
- View/download PDF
21. Serum glial fibrillary acidic protein is a predictor of brain metastases in patients with metastatic breast cancer.
- Author
-
Darlix A, Hirtz C, Mollevi C, Ginestet N, Tiers L, Jacot W, and Lehmann S
- Subjects
- Adult, Brain Neoplasms blood, Brain Neoplasms therapy, Breast Neoplasms blood, Breast Neoplasms therapy, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Middle Aged, Prognosis, ROC Curve, Retrospective Studies, Survival Rate, Biomarkers, Tumor blood, Brain Neoplasms secondary, Breast Neoplasms pathology, Glial Fibrillary Acidic Protein blood
- Abstract
In patients with metastatic breast cancer (MBC), brain metastases (BM) are associated with high morbidity and mortality. However, there is no validated serum biomarker that accurately predicts BM occurrence in these patients, and the role of serum biomarkers for prognosis remains unclear. Here, we evaluated the association of neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1 (UCHL1), glial fibrillary acidic protein (GFAP) and tau serum levels with BM presence and prognosis in patients with MBC. In serum samples from patients with MBC with (n = 100) and without BM (n = 47), we measured the biomarker serum levels using single molecule array (Simoa) technology (Neurology-4-Plex assay). To evaluate their accuracy to identify patients with BM, we determined the receiver operating characteristic curve and the area under the curve (AUC) for each biomarker and calculated their sensitivity and specificity. The median serum levels of NfL, UCHL1, tau and GFAP were significantly higher in patients with BM. The AUC for GFAP (0.82, 95% confidence interval [CI] 0.75-0.88) was significantly higher than those of the other biomarkers considered independently. Using the medians as cutoff values, elevated serum levels of NfL, UCHL1, tau and GFAP were associated with BM in univariate analysis, but only high GFAP levels in multivariate analysis (odd ratio 23.4, 95% CI 6.8-80.5, P < .001). Elevated serum GFAP levels were independently associated with poor outcome. GFAP outperforms NfL, UCHL1 and tau as diagnostic and prognostic factor of BM in patients with MBC. These results must now be validated in an independent cohort of patients., (© 2021 UICC.)
- Published
- 2021
- Full Text
- View/download PDF
22. Tau protein in cerebrospinal fluid: a novel biomarker of the time of death?
- Author
-
Peyron PA, Hirtz C, Baccino E, Ginestet N, Tiers L, Martinez AY, Lehmann S, and Delaby C
- Subjects
- Aged, Aged, 80 and over, Biomarkers cerebrospinal fluid, Female, Humans, Male, Middle Aged, Postmortem Changes, tau Proteins cerebrospinal fluid
- Abstract
Background: Tau proteins are recognized biomarkers of neurodegeneration and neuronal damage in the cerebrospinal fluid (CSF). It has also been suggested that these CSF proteins could increase post-mortem due to neuronal death. The aim of this study was to investigate the changes in CSF total and phosphorylated tau (p-tau) levels in the early post-mortem interval (PMI), to determine whether these proteins could be relevant biomarkers of time since death., Methods: Tau and p-tau levels were measured by ELISA in lumbar and cisternal CSF samples from 82 corpses (46 men, 36 women, mean age: 72.4 ± 15.2 years) with a PMI < 12 h. Forty-eight of them were considered neurologically healthy at the time of death. Rectal and tympanic temperatures were also measured in 37 individuals, and two validated temperature-based methods of PMI estimation were applied (Henssge's nomogram and Baccino's method)., Results: CSF tau and p-tau levels were significantly increased, with respective median values of 3315 pg/mL and 68.5 pg/mL in the whole cohort, while lower but still increased levels were observed in neurologically healthy patients. Sub-occipital punctures systematically provided higher tau and p-tau values (p < 0.0001). Despite a great inter-individual variability, the concentrations of both biomarkers were positively correlated with the early PMI, with the highest correlation for cisternal p-tau (r = 0.50, p < 0.0001 in the whole cohort; r = 0.58, p = 0.0003 in the neurologically healthy patients). Higher levels of CSF biomarkers were observed for PMI > 6 h versus PMI ≤ 6 h, the discriminatory power of the biomarkers being higher in the subgroup of neurologically healthy patients. Based on cut-off values obtained by ROC curve analysis, the CSF biomarkers could rectify or adjust the time interval provided by the temperature-based methods in a significant number of cases. A predictive model combining tympanic temperature and cisternal tau values was found to be particularly accurate to assign individuals according to their PMI (≤ or > 6 h), with a Se of 83% and a Sp of 100% (AUC = 0.95)., Conclusion: Our findings suggest that CSF tau and p-tau proteins could serve as potential biomarkers of time since death, in association with tympanic temperature. The practical applicability of such an integrated approach has to be assessed by further studies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2021
- Full Text
- View/download PDF
23. Sample Pooling and Inflammation Linked to the False Selection of Biomarkers for Neurodegenerative Diseases in Top-Down Proteomics: A Pilot Study.
- Author
-
Molinari N, Roche S, Peoc'h K, Tiers L, Séveno M, Hirtz C, and Lehmann S
- Abstract
Proteomic technologies have been recently adapted to the new field of clinical proteomics. The origin of errors and biases has been well-identified in the pre-analytical steps, leading to the measurement of clinical analytes. One possible source of inadequacy in clinical proteomics is linked to sample pooling. This practice is usually related to low sample availability, variability, experiment time/cost. In this study, we first asked whether sample pooling in top-down proteomics is suitable to obtain a relevant biological average. Our second objective was to identify inflammatory biomarkers of outlier samples in our population of Creutzfeldt-Jakob disease patients. Our results demonstrated that, in a proteomics study, sample pooling as well as the inflammation status was an important source of errors: missed detection of biomarkers and false identification of others. Pooled samples were not equivalent to the average of biological values. In addition, this procedure reduced the statistical value of the identified biomarkers due to a stabilization of their standard deviation and rendered outlier samples difficult to detect. We identified serum amyloid A as a candidate biomarker of outlier samples. The presence of this protein, which could be explained by inflammatory processes, induced major modifications in the sample profiles.
- Published
- 2018
- Full Text
- View/download PDF
24. Relevance of Aβ42/40 Ratio for Detection of Alzheimer Disease Pathology in Clinical Routine: The PLM R Scale.
- Author
-
Lehmann S, Delaby C, Boursier G, Catteau C, Ginestet N, Tiers L, Maceski A, Navucet S, Paquet C, Dumurgier J, Vanmechelen E, Vanderstichele H, and Gabelle A
- Abstract
Background: Cerebrospinal fluid (CSF) biomarkers (Aβ peptides and tau proteins) improved the diagnosis of Alzheimer's disease (AD) in research and clinical settings. We previously described the PLM-scale (Paris-Lille-Montpellier study), which combines Aβ42, tau, and phosphorylated ptau(181) biomarkers in an easy to use and clinically relevant way. The purpose of this work is to evaluate an optimized PLM
R- scale (PLM ratio scale) that now includes the Aβ42/Aβ40 ratio to detect AD versus non-AD (NAD) participants in clinical routine of memory centers. Methods: Both scales were compared using 904 participants with cognitive impairment recruited from two independent cohorts (Mtp-1 and Mtp-2). The CSF Aβ42/Aβ40 ratio was measured systematically in Mtp-1, and only on biologically discordant cases in Mtp-2. Two different ELISA kit providers were also employed. The distribution of AD and NAD patients and the discrepancies of biomarker profiles were computed. Receiver Operating Characteristic curves were used to represent clinical sensitivity and specificity for AD detection. The classification of patients with the net reclassification index (NRI) was also evaluated. Results: Nine hundred and four participants (342 AD and 562 NAD) were studied; 400 in Mtp-1 and 504 in Mtp-2. For AD patients, the mean CSF Aβ42 and CSF Aβ42/40 ratio was 553 ± 216 pg/mL and 0.069 ± 0.022 pg/mL in Mtp-1 and 702 ± 335 pg/mL and 0.045 ± 0.020 pg/mL in Mtp-2. The distribution of AD and NAD differed between the PLM and the PLMR scales ( p < 0.0001). The percentage AD well-classified (class 3) increased with PLMR from 38 to 83% in Mpt-1 and from 33 to 53% in Mpt-2. A sharp reduction of the discordant profiles going from 34 to 16.3% and from 37.5 to 19.8%, for Mtp-1 and Mtp-2 respectively, was also observed. The AUC of the PLMR scale was 0.94 in Mtp-1 and 0.87 in Mtp-2. In both cohorts, the PLMR outperformed CSF Aβ42 or Aβ42/40 ratio. The diagnostic performance was improved with the PLMR with an NRI equal to 44.3% in Mtp-1 and 28.8% in Mtp-2. Conclusion: The integration of the Aβ42/Aβ40 ratio in the PLMR scale resulted in an easy-to-use tool which reduced the discrepancies in biologically doubtful cases and increased the confidence in the diagnosis in memory center.- Published
- 2018
- Full Text
- View/download PDF
25. What sample preparation should be chosen for targeted MS monoclonal antibody quantification in human serum?
- Author
-
Vialaret J, Broutin S, Pugnier C, Santelé S, Jaffuel A, Barnes A, Tiers L, Pelletier L, Lehmann S, Paci A, and Hirtz C
- Subjects
- Amino Acid Sequence, Antibodies, Monoclonal chemistry, Antibodies, Monoclonal immunology, Antibodies, Monoclonal isolation & purification, Chromatography, Liquid, Enzyme-Linked Immunosorbent Assay, Humans, Limit of Detection, Proteolysis, Staphylococcal Protein A immunology, Analytic Sample Preparation Methods methods, Antibodies, Monoclonal blood, Mass Spectrometry
- Abstract
Aim: Monoclonal antibody-based treatment of cancer has been established as one of the most successful therapeutic strategies., Materials & Methods: In this work, we developed a workflow based on an automated protein-A capture and LC-MS/MS analysis to quantify bevacizumab on patient serum during treatment. This analytical approach was fully validated and compared with a commercially available Monoclonal antibody-based treatment preparation (nanosurface and molecular-orientation limited kit)., Results: The analytical comparison of the two preparative workflows based on protein-A capture gave similar results with a better lower limit of quantification for the nanosurface and molecular-orientation limited kit (0.26986 vs 1.9565 μg/ml)., Conclusion: LC-MS/MS has clear advantages compared with ELISA when considering method development time, multiplexing capacities and absolute quantification with internal standardization.
- Published
- 2018
- Full Text
- View/download PDF
26. Clinical perspectives of dried blood spot protein quantification using mass spectrometry methods.
- Author
-
Lehmann S, Picas A, Tiers L, Vialaret J, and Hirtz C
- Subjects
- Humans, Dried Blood Spot Testing, Mass Spectrometry
- Abstract
Although dried blood spot (DBS) sampling methods have been used since the 1960s, they have recently attracted renewed interest because of the development of new clinical applications. In addition to their other advantages, DBS methods can now be used to quantify many blood proteins using the latest highly sensitive and robust, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) approaches such as multiple reaction monitoring. The DBS blood sampling approach could provide a useful alternative means of conducting blood sampling for routine clinical purposes and patients' follow-up. In this review, we examine the current use of DBS for LC-MS/MS protein quantification in clinical settings and discuss potential clinical applications.
- Published
- 2017
- Full Text
- View/download PDF
27. Human S100A10 plays a crucial role in the acquisition of the endometrial receptivity phenotype.
- Author
-
Bissonnette L, Drissennek L, Antoine Y, Tiers L, Hirtz C, Lehmann S, Perrochia H, Bissonnette F, Kadoch IJ, Haouzi D, and Hamamah S
- Subjects
- Adult, Apoptosis, Cell Adhesion, Cell Movement, Cell Proliferation, Cell Shape, Cells, Cultured, Down-Regulation, Embryo Implantation, Epithelial Cells metabolism, Female, Gene Knockdown Techniques, Gene Silencing, Humans, Mass Spectrometry, Menstrual Cycle, Phenotype, Pregnancy, Proteomics, Stromal Cells metabolism, Transcriptome genetics, Trophoblasts cytology, Annexin A2 metabolism, Endometrium metabolism, S100 Proteins metabolism
- Abstract
In assisted reproduction, about 30% of embryo implantation failures are related to inadequate endometrial receptivity. To identify molecules involved in endometrial receptivity acquisition, we investigated, using a SELDI-TOF approach, the protein expression profile of early-secretory and mid-secretory endometrium samples. Among the proteins upregulated in mid-secretory endometrium, we investigated the function of S100A10 in endometrial receptivity and implantation process. S100A10 was expressed in epithelial and stromal cells of the endometrium of fertile patients during the implantation windows. Conversely, it was downregulated in the mid-secretory endometrium of infertile patients diagnosed as non-receptive. Transcriptome analysis of human endometrial epithelial and stromal cells where S100A10 was silenced by shRNA revealed the deregulation of 37 and 256 genes, respectively, related to components of the extracellular matrix and intercellular connections. Functional annotations of these deregulated genes highlighted alterations of the leukocyte extravasation signaling and angiogenesis pathways that play a crucial role during implantation. S100A10 silencing also affected the migration of primary endometrial epithelial and stromal cells, decidualization and secretory transformation of primary endometrial stromal cells and epithelial cells respectively, and promoted apoptosis in serum-starved endometrial epithelial cells. Our findings identify S100A10 as a player in endometrial receptivity acquisition.
- Published
- 2016
- Full Text
- View/download PDF
28. Development of new quantitative mass spectrometry and semi-automatic isofocusing methods for the determination of Apolipoprotein E typing.
- Author
-
Hirtz C, Vialaret J, Nouadje G, Schraen S, Benlian P, Mary S, Philibert P, Tiers L, Bros P, Delaby C, Gabelle A, and Lehmann S
- Subjects
- Apolipoprotein E2 blood, Apolipoprotein E3 blood, Apolipoprotein E4 blood, Genotype, Humans, Isoelectric Focusing instrumentation, Phenotype, Software, Tandem Mass Spectrometry instrumentation, Apolipoprotein E2 genetics, Apolipoprotein E3 genetics, Apolipoprotein E4 genetics, Automation, Isoelectric Focusing methods, Tandem Mass Spectrometry methods
- Abstract
Background: Apolipoprotein E (Apo E) is a 36 Kda glycoprotein involved in lipid transport. It exists in 3 major isoforms: E2, E3 and E4. ApoE status is known to be a major risk factor for late-onset Alzheimer's and cardiovascular diseases. Genotyping is commonly used to obtain ApoE status but can show technical issues with ambiguous determinations. Phenotyping can be an alternative, not requiring genetic material. We evaluated the ability to accurately type ApoE isoforms by 2 phenotyping tests in comparison with genotyping., Methods: Two phenotyping techniques were used: (1) LC-MS/MS detection of 4 ApoE specific peptides (6490 Agilent triple quadripole): After its denaturation, serum was either reduced and alkylated, or only diluted, and then trypsin digested. Before analysis, desalting, evaporation and resuspension were performed. (2) Isoelectric focusing and immunoprecipitation: serum samples were neuraminidase digested, delipidated and electrophoresed on Hydragel ApoE (Sebia agarose gel) using Hydrasys 2 Scan instrument (Sebia, Lisses, France). ApoE isoforms bands were directly immunofixed in the gel using a polyclonal anti human ApoE antibody. Then, incubation of the gel with HRP secondary antibody followed by TTF1/TTF2 substrate allowed the visualization of ApoE bands. The results of the two techniques were compared to genotyping., Results: Sera from 35 patients previously genotyped were analyzed with the 2 phenotyping techniques. 100% concordance between both phenotyping assays was obtained for the tested phenotypes (E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, E4/E4). When compared to genotyping, 3 samples were discordant. After reanalyzing them by both phenotyping tests and DNA sequencing, 2/3 discrepancies were confirmed. Those can be explained by variants or rare ApoE alleles or by unidentified technical issues. 102 additional samples were then tested on LC-MS/MS only and compared to genotyping. The data showed 100% concordance., Conclusion: Our 2 phenotyping methods represent a valuable alternative to genotyping. LC-MS/MS has the advantage of being fully specific, with identification of the different isoforms and can be considered as a reference method. Sebia isofocusing technique was concordant with LC-MS/MS. Plus, it is a rapid, semi-automated assay that can be easily implemented in clinical laboratories., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
29. Development and validation of dried matrix spot sampling for the quantitative determination of amyloid β peptides in cerebrospinal fluid.
- Author
-
Delaby C, Gabelle A, Meynier P, Loubiere V, Vialaret J, Tiers L, Ducos J, Hirtz C, and Lehmann S
- Subjects
- Alzheimer Disease diagnosis, Biomarkers cerebrospinal fluid, Dried Blood Spot Testing, Humans, Amyloid beta-Peptides cerebrospinal fluid, Enzyme-Linked Immunosorbent Assay, Peptide Fragments cerebrospinal fluid
- Abstract
Background: The use of dried blood spots on filter paper is well documented as an affordable and practical alternative to classical venous sampling for various clinical needs. This technique has indeed many advantages in terms of collection, biological safety, storage, and shipment. Amyloid β (Aβ) peptides are useful cerebrospinal fluid (CSF) biomarkers for Alzheimer disease diagnosis. However, Aβ determination is hindered by preanalytical difficulties in terms of sample collection and stability in tubes., Methods: We compared the quantification of Aβ peptides (1-40, 1-42, and 1-38) by simplex and multiplex ELISA, following either a standard operator method (liquid direct quantification) or after spotting CSF onto dried matrix paper card., Results: The use of dried matrix spot (DMS) overcame preanalytical problems and allowed the determination of Aβ concentrations that were highly commutable (Bland-Altman) with those obtained using CSF in classical tubes. Moreover, we found a positive and significant correlation (r2=0.83, Pearson coefficient p=0.0329) between the two approaches., Conclusions: This new DMS method for CSF represents an interesting alternative that increases the quality and efficiency in preanalytics. This should enable the better exploitation of Aβ analytes for Alzheimer's diagnosis.
- Published
- 2014
- Full Text
- View/download PDF
30. From "clinical proteomics" to "clinical chemistry proteomics": considerations using quantitative mass-spectrometry as a model approach.
- Author
-
Lehmann S, Poinot P, Tiers L, Junot C, Becher F, and Hirtz C
- Subjects
- Humans, Mass Spectrometry, Models, Biological, Biomarkers, Tumor, Chemistry, Clinical, Proteomics trends
- Abstract
Clinical Proteomics biomarker discovery programs lead to the selection of putative new biomarkers of human pathologies. Following an initial discovery phase, validation of these candidates in larger populations is a major task that recently started relying upon the use of mass spectrometry approaches, especially in cases where classical immune-detection methods were lacking. Thanks to highly sensitive spectrometers, adapted measurement methods like selective reaction monitoring (SRM) and various pre-fractionation methods, the quantitative detection of protein/peptide biomarkers in low concentrations is now feasible from complex biological fluids. This possibility leads to the use of similar methodologies in clinical biology laboratories, within a new proteomic field that we shall name "Clinical Chemistry Proteomics" (CCP). Such evolution of Clinical Proteomics adds important constraints with regards to the in vitro diagnostic (IVD) application. As measured values of analytes will be used to diagnose, follow-up and adapt patient treatment on a routine basis; medical utility, robustness, reference materials and clinical feasibility are among the new issues of CCP to consider.
- Published
- 2011
- Full Text
- View/download PDF
31. Correlations between soluble α/β forms of amyloid precursor protein and Aβ38, 40, and 42 in human cerebrospinal fluid.
- Author
-
Gabelle A, Roche S, Gény C, Bennys K, Labauge P, Tholance Y, Quadrio I, Tiers L, Gor B, Chaulet C, Vighetto A, Croisile B, Krolak-Salmon P, Touchon J, Perret-Liaudet A, and Lehmann S
- Subjects
- Biomarkers cerebrospinal fluid, Enzyme-Linked Immunosorbent Assay, Humans, Alzheimer Disease cerebrospinal fluid, Amyloid beta-Peptides cerebrospinal fluid, Amyloid beta-Protein Precursor cerebrospinal fluid, Peptide Fragments cerebrospinal fluid
- Abstract
Cerebrospinal fluid (CSF) biomarkers are now widely used for diagnosis of Alzheimer disease (AD) in atypical clinical forms, for differential and early diagnosis, or for stratification of patients in clinical trials. Among these biomarkers, different forms of amyloid peptides (Aβ) produced by the cleavage of a transmembrane precursor protein called APP (amyloid precursor protein) have a major role. Aβ peptides exist in different length the most common ones having 40 (Aβ40), 42 (Aβ42), or 38 (Aβ38) amino acids in length. APP processing by gamma-secretase releases also an amino-terminal secreted fragment called sAβPP-beta while an alternative nonamyloidogenic cleavage of APP, through an alpha-secretase, liberates another fragment called sAβPP-alpha. To decipher the molecular and pathological mechanisms leading to the production and the detection of these entities is essential for the comprehension and the prevention of AD. In this report, we present the results of the multiplex measurement of CSF Aβ38, Aβ40, Aβ42, sAβPP-alpha, and sAβPP-beta in 60 patients mostly with dementia eventually segregated between neurochemical dementia diagnostic (NDD) positive and negative groups. The NDD classification was based on our routine Tau, P-tau(181), and Aβ(42) cutoff values. We confirmed previous findings regarding the correlation between sAβPP-alpha and sAβPP-beta, as well as the potential interest of these new biomarkers. We also studied the correlation between sAβPPs and Aβ peptides, as well as between Aβ peptides themselves. We observed a strong correlation between Aβ38 and sAβPP-beta which suggested that the production of this peptide was in direct relation with β secretase activities. We also reported a strong correlation between Aβ38 and Aβ40, while Aβ42 was correlated to these fragments only in nonpathological situations. These results enlighten the complex relationships between these molecular markers in both physiological and pathological situations. Our results are important for the further use of these analytes for AD diagnosis as well as for validating the cell biological hypotheses of APP processing and Aβ fragment production., (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
32. Regulation of CXCR/IL-8 in human airway epithelial cells.
- Author
-
Gras D, Tiers L, Vachier I, de Senneville LD, Bourdin A, Godard P, Lehman S, and Chanez P
- Subjects
- Antibodies immunology, Antibodies pharmacology, Bronchi cytology, Bronchi metabolism, Epithelial Cells cytology, Epithelial Cells drug effects, Gene Expression genetics, Humans, Intercellular Adhesion Molecule-1 metabolism, Interleukin-6 metabolism, Interleukin-8 pharmacology, Peptides analysis, Peptides metabolism, Proteins analysis, Proteins metabolism, Receptors, CXCR genetics, Receptors, CXCR immunology, Receptors, Interleukin-8A genetics, Receptors, Interleukin-8A immunology, Receptors, Interleukin-8A metabolism, Receptors, Interleukin-8B genetics, Receptors, Interleukin-8B immunology, Receptors, Interleukin-8B metabolism, Respiratory Mucosa cytology, Respiratory Mucosa metabolism, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Epithelial Cells metabolism, Interleukin-8 metabolism, Lung cytology, Receptors, CXCR metabolism
- Abstract
Background: Severe asthma is characterized by neutrophilic inflammation and high levels of interleukin (IL)-8. Airway epithelial cells play a pivotal role in the pathogenesis and chronicity of asthma. The objective of this work was to determine whether CXC receptors were involved in human small airway epithelial cell (SAEC) activity by incubating them with IL-8; the investigation also included a proteomic approach., Methods: IL-6 and intercellular adhesion molecule-1 (ICAM-1) were assessed by ELISA and flow cytometry, respectively. CXCR-1 and CXCR-2 receptor mRNA and protein expressions were analyzed by RT-PCR, immunocytochemistry and flow cytometry. Cells were incubated with different concentrations (0-100 ng/ml) of IL-8. The involvement of both receptors was assessed using specific antibodies., Results: Only the CXCR-1 receptor was expressed in SAECs. IL-8 (50 ng/ml, 12 h) induced the release of IL-6 and had no effect on ICAM-1. Supernatants analyzed by surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) showed very weak differences in peptide profiles. Interestingly, 4,820-m/z peptide release was detected in the presence of IL-8 and abolished by CXCR-1 antibody., Discussion: The present study illustrated the fact that IL-8 mediated by CXCR-1 increased IL-6. We also highlight the usefulness of SELDI ProteinChip technology to confirm the potential variation of peptide profile. Moreover, we were able to detect the 4,820-m/z peptide secreted in vitro by human airway epithelial cells induced by IL-8 via CXCR-1 receptor. Determination of the protein secretion profile in response to inflammatory stimuli could be an important therapeutic strategy in severe asthma., (Copyright 2009 S. Karger AG, Basel.)
- Published
- 2010
- Full Text
- View/download PDF
33. Depletion of one, six, twelve or twenty major blood proteins before proteomic analysis: the more the better?
- Author
-
Roche S, Tiers L, Provansal M, Seveno M, Piva MT, Jouin P, and Lehmann S
- Subjects
- Blood Proteins isolation & purification, Cluster Analysis, Electrophoresis, Gel, Two-Dimensional, Electrophoresis, Polyacrylamide Gel, Haptoglobins chemistry, Humans, Immunoglobulin A chemistry, Immunoglobulin G chemistry, Peptides chemistry, Proteins chemistry, Proteome, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Transferrin chemistry, alpha 1-Antitrypsin chemistry, Blood Proteins chemistry, Proteomics instrumentation, Proteomics methods
- Abstract
Depletion of major blood proteins is one of the most promising approaches to access low abundant biomarkers using proteomics. Immunocapture columns often used for this purpose exist in different formats depending on the number of major proteins removed. In this article, we compared the relative interest of depleting either one (albumin), six (albumin, IgG, IgA, transferrin, alpha1-antitrypsin, and haptoglobin), twelve (the previous six and apo A-I and -II, orosomucoid, alpha2-macroglobulin, fibrinogen, IgM) or twenty blood proteins (the previous twelve and IgD, ceruloplasmin, apo B, complement C1q, C3, C4, plasminogen, and prealbumin). Such study raises interesting issues related to the reproducibility, practicability, specificity of the immunocapture, and to the impact of removing not only the selected molecules, but also associated peptides and proteins. Depleted sera were here analysed using different proteomic approaches, including two dimensional electrophoresis and SELDI-TOF. Altogether, our results clearly confirmed the interest of depleting major blood proteins for the proteomic detection of low abundant components. However, we observed that increasing the number of depleted proteins from twelve to twenty had a limited beneficial impact and might increase drawbacks in removing associated peptides and proteins. This conclusion is however related to the technologies that we have used, and we believe that it is necessary to adapt the immunocapture to the analytical method employed, and to the ratio between wanted and unwanted proteins removed.
- Published
- 2009
- Full Text
- View/download PDF
34. Autoantibody profiling on high-density protein microarrays for biomarker discovery in the cerebrospinal fluid.
- Author
-
Roche S, Dauvilliers Y, Tiers L, Couderc C, Piva MT, Provansal M, Gabelle A, and Lehmann S
- Subjects
- Humans, Autoantibodies cerebrospinal fluid, Biomarkers cerebrospinal fluid, Protein Array Analysis methods
- Abstract
Detection of autoantibodies, which are involved in tissue injury and/or the reporters from the immune system of various pathologic events, has an important potential for diagnosis, prognosis, disease staging and treatment selection. This explains the interest for new proteomics technologies, such as the high-density protein microarray used here, that allow a high-throughput, multiplexed and sensitive detection of specific autoantibodies. So far, most of the research has been performed on blood. In this note, we focus on the cerebrospinal fluid in an attempt to address autoimmune events associated with neurological disorders. Importantly, the cerebrospinal fluid is quite different from the blood in terms of protein composition and concentration. We had therefore to adapt the available blood protocols. We present here the result of our optimization that will be useful to carry out full scale immunological studies of the cerebrospinal fluid using high-density protein microarrays.
- Published
- 2008
- Full Text
- View/download PDF
35. Interest of major serum protein removal for Surface-Enhanced Laser Desorption/Ionization - Time Of Flight (SELDI-TOF) proteomic blood profiling.
- Author
-
Roche S, Tiers L, Provansal M, Piva MT, and Lehmann S
- Abstract
Background: Surface-Enhanced Laser Desorption/Ionization - Time Of Flight (SELDI-TOF) has been proposed as new approach for blood biomarker discovery. However, results obtained so far have been often disappointing as this technique still has difficulties to detect low-abundant plasma and serum proteins., Results: We used a serum depletion scheme using chicken antibodies against various abundant proteins to realized a pre-fractionation of serum prior to SELDI-TOF profiling. Depletion of major serum proteins by immunocapture was confirmed by 1D and 2D gel electrophoresis. SELDI-TOF analysis of bound and unbound (depleted) serum fractions revealed that this approach allows the detection of new low abundant protein peaks with satisfactory reproducibility., Conclusion: The combination of immunocapture and SELDI-TOF analysis opens new avenues into proteomic profiling for the discovery of blood biomarkers.
- Published
- 2006
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.