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1. Effects of Immunoglobulins G From Systemic Sclerosis Patients in Normal Dermal Fibroblasts: A Multi-Omics Study

Author

Aurélien Chepy, Solange Vivier, Fabrice Bray, Camille Ternynck, Jean-Pascal Meneboo, Martin Figeac, Alexandre Filiot, Lucile Guilbert, Manel Jendoubi, Christian Rolando, David Launay, Sylvain Dubucquoi, Guillemette Marot, Vincent Sobanski, Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 (MSAP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), MOdel for Data Analysis and Learning (MODAL), Laboratoire Paul Painlevé (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-École polytechnique universitaire de Lille (Polytech Lille), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Université de Lille, CHU Lille, Institute for Translational Research in Inflammation - U 1286 [INFINITE (Ex-Liric)], Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286, Miniaturisation pour la Synthèse, l'Analyse et la Protéomique (MSAP) - USR 3290, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS], Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP], MOdel for Data Analysis and Learning [MODAL], METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, and Institut Universitaire de France [IUF]

Subjects
systemic sclerosis, multi-omics analysis, autoantibodies, proteomics, transcriptomics, Scleroderma, Systemic, Proteome, [SDV]Life Sciences [q-bio], Immunology, Fibroblasts, Tandem Mass Spectrometry, Immunoglobulin G, Humans, Immunology and Allergy, Chromatography, Liquid
Abstract

International audience; Autoantibodies (Aabs) are frequent in systemic sclerosis (SSc). Although recognized as potent biomarkers, their pathogenic role is debated. This study explored the effect of purified immunoglobulin G (IgG) from SSc patients on protein and mRNA expression of dermal fibroblasts (FBs) using an innovative multi-omics approach. Dermal FBs were cultured in the presence of sera or purified IgG from patients with diffuse cutaneous SSc (dcSSc), limited cutaneous SSc or healthy controls (HCs). The FB proteome and transcriptome were explored using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and microarray assays, respectively. Proteomic analysis identified 3,310 proteins. SSc sera and purified IgG induced singular protein profile patterns. These FB proteome changes depended on the Aab serotype, with a singular effect observed with purified IgG from anti-topoisomerase-I autoantibody (ATA) positive patients compared to HC or other SSc serotypes. IgG from ATA positive SSc patients induced enrichment in proteins involved in focal adhesion, cadherin binding, cytosolic part, or lytic vacuole. Multi-omics analysis was performed in two ways: first by restricting the analysis of the transcriptomic data to differentially expressed proteins; and secondly, by performing a global statistical analysis integrating proteomics and transcriptomics. Transcriptomic analysis distinguished 764 differentially expressed genes and revealed that IgG from dcSSc can induce extracellular matrix (ECM) remodeling changes in gene expression profiles in FB. Global statistical analysis integrating proteomics and transcriptomics confirmed that IgG from SSc can induce ECM remodeling and activate FB profiles. This effect depended on the serotype of the patient, suggesting that SSc Aab might play a pathogenic role in some SSc subsets.

Published
2022
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2. Is CCL18 a potential biomarker of type-2 asthma endotypes?

Author

Pascal Chanez, Jonathan Giovannelli, Camille Taillé, Anne Tsicopoulos, Cécile Chenivesse, Patrick Berger, Joanne Balsamelli, Arnaud Bourdin, Helen Fouquet, Marina Pretolani, Antoine Magnan, Thierry Perez, S. Fry, Patricia de Nadai, Clinique de pneumologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie et Immuno-Allergologie [CHU LIlle], Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'explorations fonctionnelles respiratoires [Lille], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de pneumologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Unité de recherche de l'institut du thorax (ITX-lab), and MORNET, Dominique

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Endotype, Multivariate analysis, phenotype, [SDV]Life Sciences [q-bio], allergic, Ligands, Gastroenterology, 03 medical and health sciences, Nasal Polyps, 0302 clinical medicine, Interquartile range, Internal medicine, CCL18, medicine, Humans, Immunology and Allergy, Eosinophilia, 030212 general & internal medicine, endotype, biomarker chemokine, Asthma, business.industry, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, 030228 respiratory system, Chemokines, CC, Pediatrics, Perinatology and Child Health, Cohort, Biomarker (medicine), Female, Chemokines, medicine.symptom, business, Biomarkers
Abstract

International audience; Objective: This exploratory cross-sectional study aimed to evaluate the associations between the chemokine ligand 18 (CCL18) blood level and phenotypic characteristics of asthma.Methods: We evaluated in a sample of 173 asthmatic adult patients from the Cohort of Bronchial obstruction and Asthma (63.4% women; median age 50 +/- interquartile range 27.5 years; median level of CCL18 was 44.1 +/- interquartile range 27.5 ng/mL) the association between CCL18 blood level and allergic features of asthma using a multivariate analysis. Results: We found an association between the log-transformed value of blood CCL18 and age (+0.7% [0.1; 1.3] per 1-year increase, p = 0.033), gender (-25.1% [-42; -3.2] in women, p = 0.029), and nasal polyposis (+38.1% [11.6; 70.9], p = 0.004). No association was observed between CCL18 level and the other main phenotypic characteristics of asthma. Conclusions: Our exploratory study suggests that CCL18 is not an effective biomarker of allergic asthma endotype but may rather be a biomarker of tissue eosinophilia as supported by its association with nasal polyposis.

Published
2020
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3. Passages in culture and stimulation conditions influence protein expression of primary fibroblasts

Author

Christian Rolando, Sylvain Dubucquoi, T. Guerrier, Vincent Sobanski, Solange Vivier, Manel Jendoubi, Maïté Balden, David Launay, Eric Hachulla, Fabrice Bray, Aurélien Chepy, Stéphanie Flament, Silvia Speca, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 (MSAP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), CSL Behring grant, and Bray, Fabrice

Subjects
Senescence, Proteomics, Scleroderma, Systemic, biology, Effector, systemic sclerosis, [SDV]Life Sciences [q-bio], Quantitative proteomics, Computational Biology, Stimulation, Transforming growth factor beta, Fibroblasts, Biochemistry, In vitro, Cell biology, [SDV] Life Sciences [q-bio], Transforming Growth Factor beta1, Cell culture, Transforming Growth Factor beta, biology.protein, Humans, Molecular Biology, Cells, Cultured
Abstract

International audience; Fibroblasts (Fb) are key effector cells in systemic sclerosis (SSc). Fb stimulation with transforming growth factor beta 1 (TGF-β1) is considered as a positive control in studies assessing fibrogenesis. The lack of standardization of TGF-β1 stimulation might be responsible for discrepancies in experiments performed in different conditions. Using quantitative proteomics analysis, we evaluated the impact of changes in experimental conditions on proteomic profiles of primary Fb. Principal component analysis (PCA) identified several groups of differentially expressed proteins influenced by cell passage, culture medium, and both concentration and duration of exposure to TGF-β1 stimulation. Bioinformatics analysis revealed that late passages expressed proteins involved in senescence. TGF-β1 concentration and time of stimulation were correlated with the expression of proteins involved in the fibrogenesis and inflammatory processes. These data underline the need for standardization of culture conditions to allow inter-data comparisons in future in vitro studies, especially when using “omics” approaches.

Published
2021
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4. Severe SARS‐CoV‐2 patients develop a higher specific T‐cell response

Author

Enagnon Kazali Alidjinou, Karine Faure, Isabelle Top, Alain Duhamel, Jacques Trauet, Emmanuelle Jeanpierre, Julien Poissy, Bertrand Meresse, Benoit Gachet, Fanny Vuotto, Pauline Varlet, Guillaume Lefèvre, Sarah Stabler, Jules Bauer, C. Yelnik, François Maggiotto, Vincent Elsermans, Arnaud Dendooven, Julien Labreuche, Sophie Susen, Mohamed Bou Saleh, David Launay, Thierry Brousseau, Sylvain Dubucquoi, Brigitte Prevost, Eloise Woitrain, Laurence Bocket, Marc Lambert, Julie Demaret, David Montaigne, Annabelle Dupont, Myriam Labalette, Laurent Dubuquoy, Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Pathogenèse virale du diabète de type 1 - ULR 3610 (Laboratoire de Virologie), Centre de référence des maladies auto-immunes systémiques rares du Nord et Nord Ouest [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), I-SITE ULNE. Grant Number: ANR-16-IDEX-0004 ULNE, ANR-16-IDEX-0004,ULNE,ULNE(2016), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille, LillOA, ULNE - - ULNE2016 - ANR-16-IDEX-0004 - IDEX - VALID, Université de Lille, CNRS, Institute for Translational Research in Inflammation - U 1286 [INFINITE (Ex-Liric)], Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Pathogenèse virale du diabète de type 1 - ULR 3610, Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE], Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD], Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017, and Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD)

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, Immunology, ELISpot, T cells, SARS‐CoV‐2, 03 medical and health sciences, 0302 clinical medicine, Antigen, Immunity, Interquartile range, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, Medicine, 030212 general & internal medicine, General Nursing, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, business.industry, SARS-CoV-2, ELISPOT, Outbreak, Original Articles, Acquired immune system, 3. Good health, Vaccination, 030104 developmental biology, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, biology.protein, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Original Article, Antibody, business, lcsh:RC581-607
Abstract

Objectives Assessment of the adaptive immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is crucial for studying long‐term immunity and vaccine strategies. We quantified IFNγ‐secreting T cells reactive against the main viral SARS‐CoV‐2 antigens using a standardised enzyme‐linked immunospot assay (ELISpot). Methods Overlapping peptide pools built from the sequences of M, N and S viral proteins and a mix (MNS) were used as antigens. Using IFNγ T‐CoV‐Spot assay, we assessed T‐cell and antibody responses in mild, moderate and severe SARS‐CoV‐2 patients and in control samples collected before the outbreak. Results Specific T cells were assessed in 60 consecutive patients (mild, n = 26; moderate, n = 10; and severe patients, n = 24) during their follow‐up (median time from symptom onset [interquartile range]: 36 days [28;53]). T cells against M, N and S peptide pools were detected in n = 60 (100%), n = 56 (93.3%), n = 55 patients (91.7%), respectively. Using the MNS mix, IFNγ T‐CoV‐Spot assay showed a specificity of 96.7% (95% CI, 88.5–99.6%) and a specificity of 90.3% (75.2–98.0%). The frequency of reactive T cells observed with M, S and MNS mix pools correlated with severity and with levels of anti‐S1 and anti‐RBD serum antibodies. Conclusion IFNγ T‐CoV‐Spot assay is a reliable method to explore specific T cells in large cohorts of patients. This test may become a useful tool to assess the long‐lived memory T‐cell response after vaccination. Our study demonstrates that SARS‐CoV‐2 patients developing a severe disease achieve a higher adaptive immune response., We quantified IFNg‐secreting T cells reactive against the M, N and S viral SARS‐CoV‐2 proteins using a standardized enzyme‐linked immunospot assay in 60 patients. The frequency of reactive T cells correlated with severity, and with levels of anti‐S1 and anti‐RBD (receptor binding domain) serum antibodies, demonstrating a higher adaptive immune response after developing a more severe disease. IFNg T‐CoV‐Spot assay may also become a useful tool to assess the long‐lived memory T cell response after vaccination.

Published
2020
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5. 'Idiopathic Eosinophilic Vasculitis': Another Side of Hypereosinophilic Syndrome? A Comprehensive Analysis of 117 Cases in Asthma-Free Patients

Author

Marie-Christine Copin, Thierry Martin, Guillaume Lefèvre, Matthieu Groh, Jean-Baptiste Gibier, Marc Lambert, François Pontana, Pierre-Yves Hatron, Myriam Labalette, Jean-François Viallard, Delphine Staumont-Sallé, F. Dezoteux, Chafika Morati-Hafsaoui, Eric Hachulla, Benjamin Lopez, Pascal DeGroote, Thomas Quemeneur, Jean-Emmanuel Kahn, Mohamed Hamidou, Amélie Leurs, Louis Terriou, Nicolas Etienne, Cécile Chenivesse, David Launay, Nicolas Schleinitz, Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), CHU Lille, Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Centre hospitalier [Valenciennes, Nord], Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôtel-Dieu de Nantes, Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Foch [Suresnes], Hôpital Ambroise Paré [AP-HP], and univOAK, Archive ouverte

Subjects
medicine.medical_specialty, Eosinophilic disorder, Aucun, Hypereosinophilia, Hypereosinophilic syndrome, Gastroenterology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Necrotizing Vasculitis, medicine, Immunology and Allergy, 030212 general & internal medicine, Arteritis, business.industry, Eosinophilic granulomatosis with polyangiitis, medicine.disease, Eosinophilic vasculitis, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, medicine.symptom, Granulomatosis with polyangiitis, business, Vasculitis, Cerebral vasculitis
Abstract

International audience; Background: The absence of asthma may rule out a diagnosis of eosinophilic granulomatosis with polyangiitis in patients with hypereosinophilic syndrome (HES) and features of vasculitis.Objective: To describe eosinophilic vasculitis (EoV) as a possible manifestation of HES in asthma-free patients.Methods: We screened our hospital database and the literature for patients with HES who met the following 4 criteria: (1) histopathological or clinical features of EoV (biopsy-proven vasculitis with predominant eosinophilic infiltration of the vessel wall and/or features of vasculitis with tissue and/or blood hypereosinophilia [absolute eosinophil count >1.5 G/L]); (2) no other obvious causes of reactive eosinophilia, organ damage, and vasculitis; (3) the absence of antineutrophil cytoplasmic antibodies; and (4) the absence of current asthma.Results: Ten of our 83 (12%) asthma-free patients with HES and 107 additional cases in the literature met the criteria for EoV. After a critical analysis of the patients' clinical and laboratory characteristics and outcomes, we identified 41 cases of single-organ EoV (coronary arteritis, n = 29; temporal arteritis, n = 8; cerebral vasculitis, n = 4). Of the remaining 76 patients with EoV, the most frequent manifestations (>10%) were cutaneous vasculitis (56%), peripheral neuropathy (24%), thromboangiitis obliterans-like disease (16%), fever (13%), central nervous system involvement (13%), deep venous thrombosis (12%), and nonasthma lung manifestations (12%). Blood hypereosinophilia more than 1.5 G/L was observed in 79% of patients, and necrotizing vasculitis was observed in 44%.Conclusions: Our results suggest that idiopathic EoV (HES-associated vasculitis) can be classified as an eosinophilic-rich, necrotizing, systemic form of vasculitis that affects vessels of various sizes in asthma-free patients.

Published
2020
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6. Expanding the phenotype of SCA19/22: Parkinsonism, cognitive impairment and epilepsy

Author

Jean-Christophe Cuvellier, Marie Delliaux, Kathy Dujardin, Delphine Dellacherie, Bernard Sablonnière, Isabelle Strubi-Vuillaume, David Devos, Luc Defebvre, Vincent Huin, Audrey Riquet, Marine Brion, Caroline Moreau, Jean-Marie Cuisset, HUIN, Vincent, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neurologie et Pathologies du Mouvement [CHU Lille], Service de neuropédiatrie [CHU Lille], Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Biologie Pathologie et Génétique, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut d'Immunologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille

Subjects
Male, 0301 basic medicine, Pediatrics, Parkinson's disease, [SDV]Life Sciences [q-bio], [SDV.GEN] Life Sciences [q-bio]/Genetics, Mesh:Adult, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SCCO]Cognitive science, Epilepsy, Mesh:Adolescent, 0302 clinical medicine, Medicine, Child, Neurogenetics, Mesh:Epilepsy/genetics, Mesh:Aged, Spinocerebellar Degenerations, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, Parkinsonism, Mesh:Spinocerebellar Degenerations/complications, Cognition, Middle Aged, Mesh:Cognitive Dysfunction/genetics, Pedigree, 3. Good health, Phenotype, Neurology, Spinocerebellar ataxia, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Adult, Mesh:Female, medicine.medical_specialty, Adolescent, Cognitive disorders, Mesh:Child, Mesh:Male, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, 03 medical and health sciences, Parkinsonian Disorders, Mesh:Middle Aged, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Mesh:80 and over, Humans, Cognitive Dysfunction, Quantitative Biology - Genomics, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Genetic testing, Genomics (q-bio.GN), [SDV.GEN]Life Sciences [q-bio]/Genetics, Cerebellar ataxia, business.industry, Mesh:Pedigree, Mesh:Phenotype, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SCCO] Cognitive science, medicine.disease, Neuropsychiatric disorder, Mesh:Humans, 030104 developmental biology, KCND3 mutation, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mesh:Parkinsonian Disorders/genetics, Parkinson''s disease, FOS: Biological sciences, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract

International audience; BACKGROUND: Spinocerebellar ataxia types 19 and 22 (SCA19/22) are rare conditions in which relatively isolated cerebellar involvement is frequently associated with cognitive impairment. Here, we report on new clinical features and provide details of the cognitive profile in two SCA19/22 families.METHODS: Two families displaying an autosomal-dominant form of cerebellar ataxia underwent clinical examinations and genetic testing.RESULTS: In addition to the classical clinical features of SCA, a wide spectrum of cognitive disorders (including visuospatial impairments) was observed. Eight patients had mild Parkinsonism, and five had epilepsy. Genetic testing showed that the KCND3 mutation (c.679_681delTTC, p.F227del) was present in both families.CONCLUSIONS: Our findings broaden the phenotypic spectrum of SCA19/22, and suggest that KCND3 should be included in the list of candidate genes for epilepsy, Parkinsonism and cognitive impairment.

Published
2017
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7. A BIOINFORMATIC MODEL DESCRIBING CROSS-REACTIVITIES BETWEEN ANTI-HLA ANTIBODIES: HELP FOR INTERPRETATION OF IMMUNIZATION PROFILES

Author

Usureau, Cedric, Varlet, Pauline, Desoutter, Judith, Guillaume, Nicolas, DESSAIVRE, Louise, CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2020

8. Antigen 5–spiked Vespula and Polistes venom extracts for Vespid allergy diagnostics: A French multicenter study

Author

Claude Lambert, M. Drouet, Françoise Bienvenu, P.A. Apoil, Charles Dzviga, Thierry Tabary, D. Mariotte, Séverine Brabant, Laurence Guilloux, François Lavaud, Anne Sarrat, Joana Vitte, Pascale Nicaise-Roland, Joëlle Birnbaum, Céline Beauvillain, Nicolas Hutt, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'immunologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Eurofins Biomnis, Laboratoire d'Immunologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Reims (CHU Reims), Unité Fonctionnelles d′Immunologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immunologie et d'immunogénétique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
Male, 0301 basic medicine, Allergy, MESH: Immunoglobulin E / blood, Wasps, Wasp Venoms, Venom, Vespula, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, MESH: Aged, 80 and over Allergens / immunology, Immunology and Allergy, MESH: Animals, MESH: Hypersensitivity / immunology, Child, Aged, 80 and over, MESH: Aged, MESH: Immunoglobulin E / immunology, MESH: Middle Aged, biology, Middle Aged, MESH: Infant, MESH: Young Adult, Child, Preschool, Female, France, Polistes, MESH: Wasp Venoms / immunology, MESH: Wasps / immunology, Adult, Pulmonary and Respiratory Medicine, Adolescent, Immunology, Young Adult, 03 medical and health sciences, Antigen, Hypersensitivity, medicine, Animals, Humans, MESH: Hypersensitivity / blood, Aged, MESH: Adolescent, MESH: Hypersensitivity / diagnosis, MESH: Humans, business.industry, MESH: Child, Preschool, Infant, MESH: Adult, Polistes spp, Allergens, Immunoglobulin E, biology.organism_classification, medicine.disease, MESH: Male, MESH: France, 030104 developmental biology, 030228 respiratory system, Multicenter study, business, MESH: Female
Abstract

International audience; Vespula and Polistes spp venom extracts (VEs) for ImmunoCAP (Thermo Fisher Scientific, Uppsala, Sweden) platforms have beenspiked, that is, enriched, with group 5 allergens since 2012. Limited information was available from the manufacturer, but small cohortshave reported altered performance for in vitro diagnostics.1,2 Herein we present the results of a French multicenter study onantigen 5–spiked Vespula and Polistes VEs compared with nonspiked VEs

Published
2018
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9. Moderate-to-severe eosinophilia induced by treatment with immune checkpoint inhibitors: 37 cases from a national reference center for hypereosinophilic syndromes and the French pharmacovigilance database

Author

Franck Morschhauser, Chouki Chenaf, Alexis B. Cortot, Nicolas Etienne, Laurent Mortier, Aurélie Grandvuillemin, Christine Le Beller, Delphine Staumont-Sallé, David Launay, Solenn Brousseau, Guillaume Lefèvre, Matthieu Groh, Johana Béné, Sophie Gautier, Jean-Emmanuel Kahn, Eric Hachulla, Alexandra Forestier, Myriam Labalette, Quentin Scanvion, service de médecine interne et immunologie clinique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de référence des maladies auto-immunes systémiques rares du Nord et Nord Ouest [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de PharmacoVigilance Nord-Pas-de-Calais [CHU Lille] (CRPV), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Centre Régional de Pharmacovigilance, de Renseignement sur le Médicament et de Pharmaco épidémiologie de Bourgogne [Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Régional de Pharmacovigilance [CHU Clermont-Ferrand] (CRPV), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Service d’oncologie thoracique et essais précoces [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Hôpital Foch [Suresnes], Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Ambroise Paré [AP-HP], The authors would like to thank all the physicians who contributed adverse drug reaction reports to the French pharmacovigilance system., Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Faculté de Médecine Henri Warembourg - Université de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-UNICANCER

Subjects
0301 basic medicine, Moderate to severe, medicine.medical_specialty, Databases, Factual, Immune checkpoint inhibitors, Immunology, Early detection, emergent adverse event, immune checkpoint inhibitors, 03 medical and health sciences, Pharmacovigilance, 0302 clinical medicine, Antineoplastic Agents, Immunological, Internal medicine, Hypereosinophilic Syndrome, Eosinophilia, Immunology and Allergy, Medicine, Humans, Adverse effect, RC254-282, business.industry, Brief Report, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, RC581-607, respiratory system, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, immune-related adverse events, Observational study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, Immunologic diseases. Allergy, business
Abstract

International audience; A better understanding of immune-related adverse events is essential for the early detection and appropriate management of these phenomena. We conducted an observational study of cases recorded at the French reference center for hypereosinophilic syndromes and in the French national pharmacovigilance database. Thirty-seven reports of eosinophilia induced by treatment with immune checkpoint inhibitors (ICIs) were included. The median [range] time to the absolute eosinophil count (AEC) peak was 15 [4─139] weeks. The median AEC was 2.7 [0.8─90.9] G/L. Eosinophil-related manifestations were reported in 21 of the 37 cases (57%). If administered, corticosteroids were always effective (n = 10 out of 10). Partial or complete remission of eosinophilia was obtained in some patients not treated with corticosteroids, after discontinuation (n = 12) or with continuation (n = 4) of the ICI. The AEC should be monitored in ICI-treated patients. If required by oncologic indications, continuation of ICI may be an option in asymptomatic hypereosinophilic patients, and in corticosteroid responders.

Published
2019
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10. Amine coupling versus biotin capture for the assessment of sulfonamide as ligands of hCA isoforms

Author

Jean-François Goossens, Tiphaine Rogez-Florent, Patrick Depreux, Pierre-Marie Danzé, Perrine Six, Anne-Sophie Drucbert, Catherine Foulon, Laurence Goossens, Sophie Duban-Deweer, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Chimie Pharmaceutique Albert Lespagnol (ICPAL), Université de Lille, Droit et Santé, Centre de Biologie Pathologie et Génétique, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), and Université d'Artois (UA)

Subjects
0301 basic medicine, Streptavidin, Biophysics, Biotin, Anticancer therapeutics, 01 natural sciences, Biochemistry, Isozyme, Sulfonamide derivatives, 03 medical and health sciences, chemistry.chemical_compound, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Surface plasmon resonance, Organic chemistry, Humans, Biotinylation, Molecular Biology, Carbonic Anhydrases, chemistry.chemical_classification, Sulfonamides, Carbonic anhydrase, 010401 analytical chemistry, Cell Biology, Binding, Enzymes, Immobilized, Combinatorial chemistry, 0104 chemical sciences, Sulfonamide, Isoenzymes, 030104 developmental biology, chemistry, Amine gas treating, Selectivity
Abstract

International audience; This work was dedicated to the development of a reliable SPR method allowing the simultaneous and quick determination of the affinity and selectivity of designed sulfonamide derivatives for hCAIX and hCAXII versus hCAII, in order to provide an efficient tool to discover drugs for anticancer therapy of solid tumors. We performed for the first time a comparison of two immobilization approaches of hCA isoforms. First one relies on the use of an amine coupling strategy, using a CM7 chip to obtain higher immobilization levels than with a CM5 chip and consequently the affinity with an higher precision (CV% < 10%). The second corresponds to a capture of proteins on a streptavidin chip, named CAP chip, after optimization of biotinylation conditions (amine versus carboxyl coupling, biotin to protein ratio). Thanks to the amine coupling approach, only hCAII and hCAXII isoforms were efficiently biotinylated to reach relevant immobilization (3000 RU and 2700 RU, respectively) to perform affinity studies. For hCAIX, despite a successful biotinylation, capture on the CAP chip was a failure. Finally, concordance between affinities obtained for the three derivatives to CAs isozymes on both chips has allowed to valid the approaches for a further screening of new derivatives.

Published
2016
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11. An Optimized Fluorescence-Based Bidimensional Immunoproteomic Approach for Accurate Screening of Autoantibodies

Author

Dutoit-Lefèvre, Virginie, Dubucquoi, Sylvain, Launay, David, Sobanski, Vincent, Dussart, Patricia, Chafey, Philippe, Broussard, Cédric, Duban-Deweer, Sophie, Vermersch, Patrick, Prin, Lionel, Lefranc, Didier, Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Centre de Biologie Pathologie et Génétique, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Médecine Interne et d'Immunologie clinique, Centre National de Référence Maladies rares-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Plateforme protéomique 3P5 [Institut Cochin] (3P5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), Service de neurologie D, This study was funded in part by‘Action deRecherche Concertée d’Initiative Régionale’(ARCirno. 09.26.0082), Programme Hospitalier deRecherche Clinique (PHRC no. 2008/1926), theassociations'Max de Vie, Max d’Amour' and'Capucine', the Société Nationale Française deMédecine Interne, Pfizer and Merck Serono. the manuscript., Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Immunologie ( EA 2686 ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ) -Institut d'Immunologie, Centre National de Référence Maladies rares-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Plateforme protéomique 3P5 [Institut Cochin] ( 3P5 ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique ( LBHE ), Université d'Artois ( UA ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Bos, Mireille

Subjects
Proteomics, Blotting, Western, lcsh:Medicine, Autoantigens, Two-Dimensional Difference Gel Electrophoresis, Mice, Image Processing, Computer-Assisted, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, Lupus Erythematosus, Systemic, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:Science, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Autoantibodies, Fluorescent Dyes, lcsh:R, Antibodies, Monoclonal, Hep G2 Cells, Carbocyanines, Molecular Weight, Immunoglobulin G, Luminescent Measurements, lcsh:Q, Isoelectric Focusing, Research Article
Abstract

International audience; Serological proteome analysis (SERPA) combines classical proteomic technology with effective separation of cellular protein extracts on two-dimensional gel electrophoresis, western blotting, and identification of the antigenic spot of interest by mass spectrometry. A critical point is related to the antigenic target characterization by mass spectrometry, which depends on the accuracy of the matching of antigenic reactivities on the protein spots during the 2D immunoproteomic procedures. The superimposition, based essentially on visual criteria of antigenic and protein spots, remains the major limitation of SERPA. The introduction of fluorescent dyes in proteomic strategies, commonly known as 2D-DIGE (differential in-gel electrophoresis), has boosted the qualitative capabilities of 2D electrophoresis. Based on this 2D-DIGE strategy, we have improved the conventional SERPA by developing a new and entirely fluorescence-based bi-dimensional immunoproteomic (FBIP) analysis, performed with three fluorescent dyes. To optimize the alignment of the different antigenic maps, we introduced a landmark map composed of a combination of specific antibodies. This methodological development allows simultaneous revelation of the antigenic, landmark and proteomic maps on each immunoblot. A computer-assisted process using commercially available software automatically leads to the superimposition of the different maps, ensuring accurate localization of antigenic spots of interest.

Published
2015
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12. Humoral Immunity Links Candida albicans Infection and Celiac Disease

Author

Corouge, Marion, Loridant, Séverine, Fradin, Chantal, Salleron, Julia, Damiens, Sébastien, Moragues, Maria Dolores, Souplet, Vianney, Jouault, Thierry, Robert, Raymond, Dubucquoi, Sylvain, Sendid, Boualem, Colombel, Jean Frédéric, Poulain, Daniel, Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord de France (COMUE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Registre EPIMAD, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Amiens-Picardie-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU), Innobioships [Lille], Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Parasitologie-Mycologie [CHRU LIlle], Institut de Microbiologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Icahn School of Medicine at Mount Sinai [New York] (MSSM), CHU Lille-CHU Lille-Fédération Hospitalière de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7-2007-2013) under HEALTH-F2-2010-260338-ALLFUN., This work is dedicated to the memory of Professor José Ponton. The authors wish to acknowledge the contribution of Nadine François for serum bank management, Dr Nicolas de Suray for his dedication and involvement to this work, Drs Nadine Cerf-Bensussan, Renata Polakowska Malika Baldwick and Bana Jabri for reviewing the manuscript and helpful discussions, and Dr Dominique Deplanque for his exchanges with the Ethics Committee of Lille University hospital., Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Amiens-Picardie, Fédération Hospitalière de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Claude Huriez [Lille], and CHU Lille-CHU Lille

Subjects
Male, BIOCHEMISTRY AND MOLECULAR BIOLOGY, MESH: Peptides/immunology, lcsh:Medicine, tissue transglutaminase, MESH: Candida albicans/physiology, Gliadin, MESH: Candidiasis/microbiology, Candida albicans, antibodies, Enzyme-linked immunoassays, lcsh:Science, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: Aged, MESH: Middle Aged, MESH: Antibodies, Fungal/isolation & purification, MESH: Candidiasis/blood, MESH: Immunoblotting, Candidiasis, MESH: Enzyme-Linked Immunosorbent Assay, Cross reactivity, invasive candidiasis, Middle Aged, in vivo, Serology, T-cell epitope, MESH: Young Adult, AGRICULTURAL AND BIOLOGICAL SCIENCES, MESH: Cross Reactions/immunology, Electrophoresis, Polyacrylamide Gel, Female, MESH: Candidiasis/complications, MESH: Antibodies, Fungal/immunology, Research Article, MESH: Candidiasis/immunology, Adult, MESH: Biomarkers/blood, Adolescent, Immunoblotting, T cells, MESH: Immunity, Humoral, chronic mucocutaneous candidiasis, Enzyme-Linked Immunosorbent Assay, Cross Reactions, Fluorescence, Fungal Proteins, Young Adult, Humans, dendritic cells, MESH: Gliadin/immunology, MESH: Celiac Disease/blood, MESH: Celiac Disease/complications, MESH: Celiac Disease/immunology, Antibodies, Fungal, Aged, MESH: Adolescent, MESH: Fungal Proteins/immunology, MESH: Humans, MEDICINE, MESH: Celiac Disease/microbiology, MESH: Fluorescence, lcsh:R, fungi, MESH: Adult, sprue, MESH: Male, Immunity, Humoral, Celiac Disease, Sequence motif analysis, gene expression, responses, lcsh:Q, Peptides, MESH: Female, Gluten, Biomarkers, MESH: Electrophoresis, Polyacrylamide Gel
Abstract

Objective The protein Hwp1, expressed on the pathogenic phase of Candida albicans, presents sequence analogy with the gluten protein gliadin and is also a substrate for transglutaminase. This had led to the suggestion that C. albicans infection (CI) may be a triggering factor for Celiac disease (CeD) onset. We investigated cross-immune reactivity between CeD and CI. Methods Serum IgG levels against recombinant Hwp1 and serological markers of CeD were measured in 87 CeD patients, 41 CI patients, and 98 healthy controls (HC). IgA and IgG were also measured in 20 individuals from each of these groups using microchips sensitized with 38 peptides designed from the N-terminal of Hwp1. Results CI and CeD patients had higher levels of anti-Hwp1 (p= 0.0005 and p= 0.004) and anti-gliadin (p= 0.002 and p= 0.0009) antibodies than HC but there was no significant difference between CeD and CI patients. CeD and CI patients had higher levels of anti-transglutaminase IgA than HC (p= 0.0001 and p= 0.0039). During CI, the increase in anti-Hwp1 paralleled the increase in anti-gliadin antibodies. Microchip analysis showed that CeD patients were more reactive against some Hwp1 peptides than CI patients, and that some deamidated peptides were more reactive than their native analogs. Binding of IgG from CeD patients to Hwp1 peptides was inhibited by gamma III gliadin peptides. Conclusions Humoral cross-reactivity between Hwp1 and gliadin was observed during CeD and CI. Increased reactivity to Hwp1 deamidated peptide suggests that transglutaminase is involved in this interplay. These results support the hypothesis that CI may trigger CeD onset in genetically-susceptible individuals. This work received the following grant support: Unit U995-2 INSERM-Lille2 University; the European Community's 7th Framework program (FP7-2007-2013) grant agreement No Health F2-2010-260338 (ALLFUN); Digest Science Foundation.

Published
2015
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13. Donor-derived CD4 + /CCR7 + T-cell impact on acute GVHD incidence following haplo-HCT after reduced intensity conditioning and posttransplant cyclophosphamide.

Author

Varlet P, Alsuliman T, Trauet J, Demaret J, Labalette M, and Yakoub-Agha I

Subjects
Acute Disease, Adult, Aged, Cyclophosphamide pharmacology, Female, Humans, Incidence, Male, Middle Aged, Retrospective Studies, Young Adult, CD4-Positive T-Lymphocytes metabolism, Cyclophosphamide therapeutic use, Graft vs Host Disease genetics, Hematopoietic Stem Cell Transplantation methods, Receptors, CCR7 metabolism, Transplantation Conditioning methods, Transplantation, Haploidentical methods
Abstract

In previous studies, we and others observed in patients undergoing HLA-matched hematopoietic cell transplantation that high proportion of donor-derived CD4 + /CCR7 + T cells were associated with an increased risk of acute GVHD without any interference in relapse incidence. We investigated the impact of donor-derived CD4 + /CCR7 + T cells on patient outcome in haploidentical settings where posttransplant cyclophosphamide is used. We analyzed T-cell subsets in grafts of 29 adult patients who underwent first haploidentical transplant following reduced intensity conditioning. The median CD4 + /CCR7 + subset proportion was 69.2% among donor CD4 + T cells. With a median follow-up of 28.1 months (range: 11.0-44.3), 16 patients (55%) developed acute GVHD; this includes 5 patients with grade 3 acute GVHD. Fifty-four percent of patients who received > 69.2% of CD4 + /CCR7 + T cells and 12% of patients who received < 69.2% CD4 + /CCR7 + T cells developed acute GVHD (p = 0.028). In multivariate analysis, a high proportion of CD4 + /CCR7 + T cells was the only factor that impacted acute GVHD (HR = 4.925, 95% CI [1.020-23.775], p = 0,047) with no impact on overall survival. Our results confirm the impact of a high proportion of CD4 + /CCR7 + T cells on acute GVHD incidence in patients undergoing haploidentical transplant despite the use of posttransplant cyclophosphamide.

Published
2019
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14. Immunomagnetic selective donor-derived CD4 + CCR7 + T cell depletion procedure for peripheral blood stem cells graft.

Author

Varlet P, Rogeau S, Trauet J, Demaret J, and Labalette M

Subjects
Blood Component Removal methods, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, Cell Engineering methods, Cells, Cultured, Graft vs Host Disease immunology, Graft vs Host Disease prevention & control, Hematologic Neoplasms immunology, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation methods, Humans, Immunologic Memory, Peripheral Blood Stem Cell Transplantation adverse effects, Peripheral Blood Stem Cells cytology, Receptors, CCR7 metabolism, Transplantation Immunology, Transplantation, Homologous, CD4-Positive T-Lymphocytes cytology, Donor Selection, Immunomagnetic Separation methods, Lymphocyte Depletion methods, Peripheral Blood Stem Cell Transplantation methods
Abstract

Purpose of the Study: While acute graft-versus-host-disease (GVHD) is a T cell-mediated disease caused by alloreactive donor T cells, we and others have highlighted that patients who received higher proportion of donor CD4 + naïve and central memory T cells expressing the chemokine receptor 7 (CCR7) more often developed acute GVHD than those who did not. Consequently, we then investigated in vitro the impact of selective CD4 + CCR7 + T cell depletion on immune reactions and showed that such a depletion reduced alloreactivity without altering acquired anti-infectious reactions. In order to translate these findings to clinic, we now developed a compliant procedure for a selective reduction of the CD4 + naïve and central memory T cell subset relevant to peripheral blood stem cell (PBSC) allografts., Patients and Methods: We performed a two-step immunomagnetic depletion of CD4 + CCR7 + T cells from ten G-CSF-mobilized PBSC apheresis samples., Results: A median of 89% (82-94%) of CD4 + CCR7 + T cells could be depleted. This allowed a marked reduction of the alloreactive immune response against allogenic dendritic cells compared with unmanipulated cells. The preservation of CD34 + cell number and the hematopoietic progenitor function were controlled. Functional tests showed that the selection procedure did not interfere with the capacity of pathogen-specific T cells to produce interferon-gamma in response to certain viral pathogens., Conclusion: Our results pave the way to a feasible procedure that can be used in patients undergoing allo-hematopoietic cell transplantation and particularly for improving haploidentical transplant results by controlling GVHD, the main immune complication., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Published
2019
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15. Naïve subset develops the most important alloreactive response among human CD4+ T lymphocytes in human leukocyte antigen-identical related setting.

Author

Chérel M, Choufi B, Trauet J, Cracco P, Dessaint JP, Yakoub-Agha I, and Labalette M

Subjects
Alleles, Antigens, Surface metabolism, CD4-Positive T-Lymphocytes metabolism, Cells, Cultured, Cytokines biosynthesis, Dendritic Cells immunology, Dendritic Cells metabolism, HLA Antigens genetics, HLA Antigens metabolism, Humans, Immunologic Memory, Inflammation Mediators metabolism, Lymphocyte Activation immunology, Siblings, T-Lymphocyte Subsets metabolism, CD4-Positive T-Lymphocytes immunology, HLA Antigens immunology, T-Lymphocyte Subsets immunology
Abstract

In longitudinal clinical studies, receiving a high percentage of allogeneic donor-derived CD4(+) CCR7(+) T cells, which include naïve and central memory subsets have been correlated with increased incidence and severity of acute GVHD. Whether naïve and central memory CD4(+) T-cell subsets contribute more or equally to alloimmune responses are still unclear in human. The aim of this study was to investigate in vitro the alloreactive response of purified naïve, central memory, and effector memory CD4(+) T-cell subsets in HLA identical setting. By coculturing monocyte-derived dendritic cells and purified CD4(+) T-cell subsets, from healthy HLA-identical male and female sibling pairs, we found that naïve CD4(+) CCR7(+) CD45RA(+) T cells developed the highest proliferative response upon stimulation by minor histocompatibility antigens and were progressively driven to produce high levels of interferon-γ, tumor necrosis factor, and interleukin-6. Comparatively, the central memory CD4(+) CCR7(+) CD45RA(neg) subset proliferated to a lower extent and produced very low amounts of pro-inflammatory cytokines while the CCR7(neg) effector memory CD4(+) subset was unresponsive. This study demonstrates the superior capacity of naïve CD4(+) T cells to mount a primary alloreactive response as compared to central memory T cells. Their proliferative response associated with a pro-inflammatory differentiation makes them potentially acute GVHD inducers. These in vitro results in line with what we have observed in clinical studies and may also lend support to approaches of partial selective T-cell depletion for GVHD prevention., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2014
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