christian drouet - Academia.edu (original) (raw)

Papers by christian drouet

Research paper thumbnail of Exploration du complexe majeur d’histocompatibilité

Research paper thumbnail of A case of remittent C1-inhibitor deficiency

Research paper thumbnail of A nationwide study of acquired C1-inhibitor deficiency in France

Medicine, 2016

Acquired angioedema (AAE) due to C1-inhibitor (C1INH) deficiency is rare. Treatment options for a... more Acquired angioedema (AAE) due to C1-inhibitor (C1INH) deficiency is rare. Treatment options for acute attacks are variable and used off-label. Successful treatment of the associated lymphoma with rituximab seems to prevent acute attacks in subjects with AAE. The aim of this study was to describe AAE manifestations, its associated diseases, and patients' responses to treatments in a representative cohort. A retrospective nationwide study was conducted in France. The inclusion criteria were recurrent angioedema attacks and an acquired decrease in functional C1INH <50% of the reference value. A total of 92 cases were included, with a median age at onset of 62 years. Facial edema and abdominal pain were the most frequent symptoms. Fifteen patients were hospitalized in the intensive care unit because of laryngeal edema, and 1 patient died. Anti-C1INH antibodies were present in 43 patients. The associated diseases were primarily non-Hodgkin lymphoma (n = 44, with 24 splenic marginal zone lymphomas) and monoclonal gammopathy of undetermined significance (n = 24). Three patients had myeloma, 1 had amyloid light-chain (of immunoglobulin) (AL) amyloidosis, 1 patient had a bronchial adenocarcinoma, and 19 patients had no associated disease. Icatibant relieved the symptoms in all treated patients (n = 26), and plasma-derived C1INH concentrate in 19 of 21 treated patients. Six patients experienced thromboembolic events under tranexamic acid prophylaxis. Rituximab prevented angioedema in 27 of 34 patients as a monotherapy or in association with chemotherapy. Splenectomy controlled AAE in 7 patients treated for splenic marginal zone lymphoma. After a median follow-up of 4.2 years, angioedema was on remission in 52 patients. AAE cases are primarily associated with indolent lymphoma-especially splenic marginal zone lymphoma-and monoclonal gammopathy of undetermined significance but not with autoimmune diseases or other conditions. Icatibant and plasma-derived C1INH concentrate control attacks; splenectomy and immunochemotherapy prevent angioedema in lymphoma setting. Abbreviations: AAE = acquired angioedema, C1INH = inhibitor of C1 esterase, HAE = hereditary angioedema, IQR = interquartile range, MGUS = monoclonal gammopathy of undetermined significance, pdC1INH = plasma-derived C1INH concentrate, SMZL = splenic marginal zone lymphoma, TA = tranexamic acid.

Research paper thumbnail of Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III

Journal of Clinical Investigation, 2015

Research paper thumbnail of Correction to Lancet Glob Health 2014; 2: e23–34

Research paper thumbnail of Complement C3 Deficiency

Encyclopedia of Medical Immunology

Research paper thumbnail of Hypersensitivity transfusion reactions to platelet concentrate: a retrospective analysis of the French hemovigilance network

Transfusion

Among labile blood products, platelet concentrates (PCs) are the leading cause of hypersensitivit... more Among labile blood products, platelet concentrates (PCs) are the leading cause of hypersensitivity transfusion reactions (HTRs). These reactions often lead to interruption of PC transfusion and can result in a prolonged transfusion process leading to significant morbidity and use of premedication and close monitoring for patients with a history of allergic transfusion reactions. The French hemovigilance database is one of the largest standardized databases providing information on HTRs following administration of labile blood products. In this study, we analyzed this database to assess the relative risk of HTR for each type of PC.

Research paper thumbnail of Angioedema: Systemic activation process during prodromes

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 2018

Research paper thumbnail of SERPING1 and F12 combined variants in a hereditary angioedema family

Annals of Allergy, Asthma & Immunology

Research paper thumbnail of Intermittent C1-Inhibitor Deficiency Associated with Recessive Inheritance: Functional and Structural Insight

Scientific reports, Jan 17, 2018

C1-inhibitor is a serine protease inhibitor (serpin) controlling complement and contact system ac... more C1-inhibitor is a serine protease inhibitor (serpin) controlling complement and contact system activation. Gene mutations result in reduced C1-inhibitor functional plasma level causing hereditary angioedema, a life-threatening disorder. Despite a stable defect, the clinical expression of hereditary angioedema is unpredictable, and the molecular mechanism underlying this variability remains undisclosed. Here we report functional and structural studies on the Arg378Cys C1-inhibitor mutant found in a patient presenting reduced C1-inhibitor levels, episodically undergoing normalization. Expression studies resulted in a drop in mutant C1-innhibitor secretion compared to wild-type. Notwithstanding, the purified proteins had similar features. Thermal denaturation experiments showed a comparable denaturation profile, but the mutant thermal stability decays when tested in conditions reproducing intracellular crowding.Our findings suggest that once correctly folded, the Arg378Cys C1-inhibitor...

Research paper thumbnail of Analyse des cas de TRALI et de TRALI possibles notifiés par le réseau d’hémovigilance de 2007 à 2013

Transfusion Clinique et Biologique

Nos objectifs etaient d’analyser les circonstances de survenue du TRALI, l’effet des mesures de p... more Nos objectifs etaient d’analyser les circonstances de survenue du TRALI, l’effet des mesures de prevention mises en œuvre et l’impact de l’utilisation des solutions de conservation de plaquettes sur l’incidence du TRALI. Dans le cas du TRALI, nous avons considere deux sous-groupes : TRALI I+ lorsqu’un donneur est porteur d’anticorps HLA et/ou HNA et que le receveur possede l’antigene correspondant, TRALI I− lorsque l’investigation immunologique est negative ou non faite. Trois cent soixante-dix-huit notifications ont ete analysees : 75 TRALI I+, 100 TRALI I− et 203 TRALI possibles. Compares a la population generale des patients transfuses, les TRALI sont plus jeunes et recoivent plus de PSL. Les situations cliniques a risque eleve de developper un TRALI que nous avons identifiees sont : hemorragie du post-partum, leucemie aigue myeloblastique, transplantation hepatique, auto et allogreffe de cellules souches hematopoietiques, polytraumatises et microangiopathie thrombotique. Les mesures de prevention du TRALI I+ en lien avec la transfusion de CP ou de PFC ont ete efficaces avec le PFC et les CPA, mais pas avec les MCP. L’utilisation de solution de conservation de plaquettes conduit a une diminution de l’incidence du TRALI dans le cas des MCP. TRALI et TRALI possible sont des entites similaires par la presentation clinique, la proportion de patients a risque, la quantite et de la qualite des PSL recus. Leur morbidite/mortalite est donc a prendre en compte globalement. Enfin, les mesures de prevention mises en œuvre n’ont pas modifie significativement l’incidence globale du TRALI. Des recherches nouvelles sont donc necessaires pour reduire l’incidence du TRALI et du TRALI possible.

Research paper thumbnail of Transfusion-related acute lung injury: critical neutrophil activation by anti-HLA-A2 antibodies for endothelial permeability

Transfusion, Jul 13, 2017

Transfusion-related acute lung injury (TRALI) is a major complication of hemotherapy that may occ... more Transfusion-related acute lung injury (TRALI) is a major complication of hemotherapy that may occur after the transfusion of any blood type component. Several clinical reports have suggested the presence of anti-HLA antibodies in the blood product. This study sought to examine the role of anti-HLA-A2 antibodies in polymorphonuclear neutrophil (PMN) activation and thus in endothelial permeability. PMN activation was assessed by both nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) activity and reactive oxygen species (ROS) production. A coculture assay of EA.hy926 endothelial cells with PMNs or differentiated-PLB-985 cells, a model of neutrophil-like cells, was performed to estimate the impact of ROS on endothelial permeability. Anti-HLA-A2 antibodies significantly increased PMN activation, with subsequent endothelial dysfunction. Phagocyte NADPH oxidase (NOX2) activity was shown to be involved in this process and ROS themselves were demonstrated to induce VE-cadhe...

Research paper thumbnail of Hereditary C1 inhibitor deficiency is associated with high spontaneous amidase activity

Molecular Immunology, 2017

Angioedema diagnosis classically targets the complement system (via C1 inhibitor (C1Inh) function... more Angioedema diagnosis classically targets the complement system (via C1 inhibitor (C1Inh) function and antigenic C4 level) and contact phase activation (via amidase activity). Bradykinin is responsible for angioedema attacks and is produced from contact phase activation secondary to failed C1Inh control. We aimed to compare the diagnostic performances of spontaneous amidase activity and antigenic C4 level in C1Inh hereditary angioedema (C1Inh-HAE) patients. Samples from 185 C1Inh-HAE patients (81 men, 104 women; confirmed by SERPING1 gene mutations) and from 99 blood donors (50 men, 49 women) were tested for C1Inh function, antigenic C4 level and spontaneous amidase activity. In the C1Inh-HAE group, antigenic C4 level was decreased (n=135) and amidase activity was increased (n=181). Receiver operating characteristic analyses showed higher diagnostic performance values for the spontaneous amidase assay compared to those of antigenic C4. The spontaneous amidase activity assay should replace antigenic C4 level testing and should be tested alongside the C1Inh function for both AE screening and follow up of HAE patients.

Research paper thumbnail of Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions

PLOS ONE, 2016

Background Angioedema without wheals (AE) is a symptom characterised by localised episodes of oed... more Background Angioedema without wheals (AE) is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh), but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases. Objectives We wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker. Methods We retrospectively investigated high molecular weight kininogen (HK) cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis. Results Circulating native HK plasma concentrations were similar in the healthy men (interquartile range: 98-175μg/mL, n = 51) and in healthy women (90-176μg/mL, n = 74), while HK cleavage was lower (p<0.001) in men (0-5%) than women (3-9%). Patients exhibited lower native HK concentration (p<10 −4 ; 21-117μg/mL, n = 31 for men; 0-84μg/mL, n = 41 for women) and higher HK cleavage (p<10 −4 ; 10-30% and 14-89%, respectively) than healthy donors. Pathological thresholds were set at: <72μg/mL native HK, >14.4% HK cleavage for men; <38μg/mL; native HK, >33.0% HK cleavage for women, with >98%

Research paper thumbnail of Method for Dosing the Control Capacity of C1INH

Research paper thumbnail of Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process

Journal of Allergy and Clinical Immunology, 2016

receives research support from University Medical Center Utrecht. A. Relan is an employee of and ... more receives research support from University Medical Center Utrecht. A. Relan is an employee of and stockholder in Pharming Technologies. S. Zeerleder receives research support from Viropharma. C. Drouet receives research support from GREPI and travel support from UCSD and the National Institutes of health. B. Zuraw serves as a consultant for Allan, Arrowhead, BioCryst, CSL Behring, Dyax, Ionis, Nektar, Shire and Salix; receives clinical research support from Ionis and received travel assistances from US HAEA. C. E. Hack is the founder of and a stockholder in Prothix BV.

Research paper thumbnail of Diagnosis and Treatment of Angioedema

Research paper thumbnail of Les protéases virales dans la famille des Flaviviridae

Virologie, Dec 31, 2002

La famille des Flaviviridae regroupe des virus enveloppes a ARN positif simple brin repartis dans... more La famille des Flaviviridae regroupe des virus enveloppes a ARN positif simple brin repartis dans trois genres : Flavivirus (fievre jaune, dengue, encephalites a tiques, japonaise et West Nile...), Hepacivirus (virus de l'hepatite C) et Pestivirus (virus de la diarrhee bovine). La maturation de l'unique polyproteine virale necessite l'intervention de proteases cellulaires (signalase et signal peptide peptidase) et de proteases codees par le genome viral. Ces dernieres sont au nombre de trois : 1) la protease a serine NS3pro, presente dans les trois genres de la famille virale, peut etre active avec differents cofacteurs : NS2B chez les Flavivirus, NS4A chez les Hepacivirus et les Pestivirus ; elle clive la proteine de capside et la majorite des proteines non structurales ; 2) le virus de l'hepatite C exprime par ailleurs la zinc-metalloprotease NS2-3 clivant NS2/NS3 ; 3) les pestivirus, la protease a cysteine Npro se trouvant a l'extremite N-terminale de la polyproteine. Les proteases virales sont des enzymes indispensables a la production virale lors d'un cycle infectieux et, dans une perspective therapeutique, elles representent des cibles strategiques en vue d'elaborer de nouvelles molecules antivirales.

Research paper thumbnail of Effect of Brefeldin a on Antigen-Presenting Cells

Research paper thumbnail of C1 Inhibitor as a glycoprotein: The influence of polysaccharides on its function and autoantibody target

Molecular immunology, Jan 18, 2016

C1 Inhibitor (C1Inh), a member of the Serine proteinase inhibitor family, is the most heavily gly... more C1 Inhibitor (C1Inh), a member of the Serine proteinase inhibitor family, is the most heavily glycosylated plasma protein. This work investigated the impact of C1Inh glycosylation on its function regarding protease targets and autoantibody binding. C1Inh deglycosylation was found to affect its function with O-linked polysaccharides, but not with N-linked polysaccharides, in controlling the contact phase but not C1s target, thus indicating the N-terminal domain's involvement in C1Inh function. Instructive samples demonstrated that O-deglycosylation strongly suppressed autoantibody binding, suggesting the polysaccharide motif is an antibody target. The autoantibodies did not directly affect C1Inh function.

Research paper thumbnail of Exploration du complexe majeur d’histocompatibilité

Research paper thumbnail of A case of remittent C1-inhibitor deficiency

Research paper thumbnail of A nationwide study of acquired C1-inhibitor deficiency in France

Medicine, 2016

Acquired angioedema (AAE) due to C1-inhibitor (C1INH) deficiency is rare. Treatment options for a... more Acquired angioedema (AAE) due to C1-inhibitor (C1INH) deficiency is rare. Treatment options for acute attacks are variable and used off-label. Successful treatment of the associated lymphoma with rituximab seems to prevent acute attacks in subjects with AAE. The aim of this study was to describe AAE manifestations, its associated diseases, and patients' responses to treatments in a representative cohort. A retrospective nationwide study was conducted in France. The inclusion criteria were recurrent angioedema attacks and an acquired decrease in functional C1INH <50% of the reference value. A total of 92 cases were included, with a median age at onset of 62 years. Facial edema and abdominal pain were the most frequent symptoms. Fifteen patients were hospitalized in the intensive care unit because of laryngeal edema, and 1 patient died. Anti-C1INH antibodies were present in 43 patients. The associated diseases were primarily non-Hodgkin lymphoma (n = 44, with 24 splenic marginal zone lymphomas) and monoclonal gammopathy of undetermined significance (n = 24). Three patients had myeloma, 1 had amyloid light-chain (of immunoglobulin) (AL) amyloidosis, 1 patient had a bronchial adenocarcinoma, and 19 patients had no associated disease. Icatibant relieved the symptoms in all treated patients (n = 26), and plasma-derived C1INH concentrate in 19 of 21 treated patients. Six patients experienced thromboembolic events under tranexamic acid prophylaxis. Rituximab prevented angioedema in 27 of 34 patients as a monotherapy or in association with chemotherapy. Splenectomy controlled AAE in 7 patients treated for splenic marginal zone lymphoma. After a median follow-up of 4.2 years, angioedema was on remission in 52 patients. AAE cases are primarily associated with indolent lymphoma-especially splenic marginal zone lymphoma-and monoclonal gammopathy of undetermined significance but not with autoimmune diseases or other conditions. Icatibant and plasma-derived C1INH concentrate control attacks; splenectomy and immunochemotherapy prevent angioedema in lymphoma setting. Abbreviations: AAE = acquired angioedema, C1INH = inhibitor of C1 esterase, HAE = hereditary angioedema, IQR = interquartile range, MGUS = monoclonal gammopathy of undetermined significance, pdC1INH = plasma-derived C1INH concentrate, SMZL = splenic marginal zone lymphoma, TA = tranexamic acid.

Research paper thumbnail of Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III

Journal of Clinical Investigation, 2015

Research paper thumbnail of Correction to Lancet Glob Health 2014; 2: e23–34

Research paper thumbnail of Complement C3 Deficiency

Encyclopedia of Medical Immunology

Research paper thumbnail of Hypersensitivity transfusion reactions to platelet concentrate: a retrospective analysis of the French hemovigilance network

Transfusion

Among labile blood products, platelet concentrates (PCs) are the leading cause of hypersensitivit... more Among labile blood products, platelet concentrates (PCs) are the leading cause of hypersensitivity transfusion reactions (HTRs). These reactions often lead to interruption of PC transfusion and can result in a prolonged transfusion process leading to significant morbidity and use of premedication and close monitoring for patients with a history of allergic transfusion reactions. The French hemovigilance database is one of the largest standardized databases providing information on HTRs following administration of labile blood products. In this study, we analyzed this database to assess the relative risk of HTR for each type of PC.

Research paper thumbnail of Angioedema: Systemic activation process during prodromes

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 2018

Research paper thumbnail of SERPING1 and F12 combined variants in a hereditary angioedema family

Annals of Allergy, Asthma & Immunology

Research paper thumbnail of Intermittent C1-Inhibitor Deficiency Associated with Recessive Inheritance: Functional and Structural Insight

Scientific reports, Jan 17, 2018

C1-inhibitor is a serine protease inhibitor (serpin) controlling complement and contact system ac... more C1-inhibitor is a serine protease inhibitor (serpin) controlling complement and contact system activation. Gene mutations result in reduced C1-inhibitor functional plasma level causing hereditary angioedema, a life-threatening disorder. Despite a stable defect, the clinical expression of hereditary angioedema is unpredictable, and the molecular mechanism underlying this variability remains undisclosed. Here we report functional and structural studies on the Arg378Cys C1-inhibitor mutant found in a patient presenting reduced C1-inhibitor levels, episodically undergoing normalization. Expression studies resulted in a drop in mutant C1-innhibitor secretion compared to wild-type. Notwithstanding, the purified proteins had similar features. Thermal denaturation experiments showed a comparable denaturation profile, but the mutant thermal stability decays when tested in conditions reproducing intracellular crowding.Our findings suggest that once correctly folded, the Arg378Cys C1-inhibitor...

Research paper thumbnail of Analyse des cas de TRALI et de TRALI possibles notifiés par le réseau d’hémovigilance de 2007 à 2013

Transfusion Clinique et Biologique

Nos objectifs etaient d’analyser les circonstances de survenue du TRALI, l’effet des mesures de p... more Nos objectifs etaient d’analyser les circonstances de survenue du TRALI, l’effet des mesures de prevention mises en œuvre et l’impact de l’utilisation des solutions de conservation de plaquettes sur l’incidence du TRALI. Dans le cas du TRALI, nous avons considere deux sous-groupes : TRALI I+ lorsqu’un donneur est porteur d’anticorps HLA et/ou HNA et que le receveur possede l’antigene correspondant, TRALI I− lorsque l’investigation immunologique est negative ou non faite. Trois cent soixante-dix-huit notifications ont ete analysees : 75 TRALI I+, 100 TRALI I− et 203 TRALI possibles. Compares a la population generale des patients transfuses, les TRALI sont plus jeunes et recoivent plus de PSL. Les situations cliniques a risque eleve de developper un TRALI que nous avons identifiees sont : hemorragie du post-partum, leucemie aigue myeloblastique, transplantation hepatique, auto et allogreffe de cellules souches hematopoietiques, polytraumatises et microangiopathie thrombotique. Les mesures de prevention du TRALI I+ en lien avec la transfusion de CP ou de PFC ont ete efficaces avec le PFC et les CPA, mais pas avec les MCP. L’utilisation de solution de conservation de plaquettes conduit a une diminution de l’incidence du TRALI dans le cas des MCP. TRALI et TRALI possible sont des entites similaires par la presentation clinique, la proportion de patients a risque, la quantite et de la qualite des PSL recus. Leur morbidite/mortalite est donc a prendre en compte globalement. Enfin, les mesures de prevention mises en œuvre n’ont pas modifie significativement l’incidence globale du TRALI. Des recherches nouvelles sont donc necessaires pour reduire l’incidence du TRALI et du TRALI possible.

Research paper thumbnail of Transfusion-related acute lung injury: critical neutrophil activation by anti-HLA-A2 antibodies for endothelial permeability

Transfusion, Jul 13, 2017

Transfusion-related acute lung injury (TRALI) is a major complication of hemotherapy that may occ... more Transfusion-related acute lung injury (TRALI) is a major complication of hemotherapy that may occur after the transfusion of any blood type component. Several clinical reports have suggested the presence of anti-HLA antibodies in the blood product. This study sought to examine the role of anti-HLA-A2 antibodies in polymorphonuclear neutrophil (PMN) activation and thus in endothelial permeability. PMN activation was assessed by both nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) activity and reactive oxygen species (ROS) production. A coculture assay of EA.hy926 endothelial cells with PMNs or differentiated-PLB-985 cells, a model of neutrophil-like cells, was performed to estimate the impact of ROS on endothelial permeability. Anti-HLA-A2 antibodies significantly increased PMN activation, with subsequent endothelial dysfunction. Phagocyte NADPH oxidase (NOX2) activity was shown to be involved in this process and ROS themselves were demonstrated to induce VE-cadhe...

Research paper thumbnail of Hereditary C1 inhibitor deficiency is associated with high spontaneous amidase activity

Molecular Immunology, 2017

Angioedema diagnosis classically targets the complement system (via C1 inhibitor (C1Inh) function... more Angioedema diagnosis classically targets the complement system (via C1 inhibitor (C1Inh) function and antigenic C4 level) and contact phase activation (via amidase activity). Bradykinin is responsible for angioedema attacks and is produced from contact phase activation secondary to failed C1Inh control. We aimed to compare the diagnostic performances of spontaneous amidase activity and antigenic C4 level in C1Inh hereditary angioedema (C1Inh-HAE) patients. Samples from 185 C1Inh-HAE patients (81 men, 104 women; confirmed by SERPING1 gene mutations) and from 99 blood donors (50 men, 49 women) were tested for C1Inh function, antigenic C4 level and spontaneous amidase activity. In the C1Inh-HAE group, antigenic C4 level was decreased (n=135) and amidase activity was increased (n=181). Receiver operating characteristic analyses showed higher diagnostic performance values for the spontaneous amidase assay compared to those of antigenic C4. The spontaneous amidase activity assay should replace antigenic C4 level testing and should be tested alongside the C1Inh function for both AE screening and follow up of HAE patients.

Research paper thumbnail of Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions

PLOS ONE, 2016

Background Angioedema without wheals (AE) is a symptom characterised by localised episodes of oed... more Background Angioedema without wheals (AE) is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh), but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases. Objectives We wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker. Methods We retrospectively investigated high molecular weight kininogen (HK) cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis. Results Circulating native HK plasma concentrations were similar in the healthy men (interquartile range: 98-175μg/mL, n = 51) and in healthy women (90-176μg/mL, n = 74), while HK cleavage was lower (p<0.001) in men (0-5%) than women (3-9%). Patients exhibited lower native HK concentration (p<10 −4 ; 21-117μg/mL, n = 31 for men; 0-84μg/mL, n = 41 for women) and higher HK cleavage (p<10 −4 ; 10-30% and 14-89%, respectively) than healthy donors. Pathological thresholds were set at: <72μg/mL native HK, >14.4% HK cleavage for men; <38μg/mL; native HK, >33.0% HK cleavage for women, with >98%

Research paper thumbnail of Method for Dosing the Control Capacity of C1INH

Research paper thumbnail of Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process

Journal of Allergy and Clinical Immunology, 2016

receives research support from University Medical Center Utrecht. A. Relan is an employee of and ... more receives research support from University Medical Center Utrecht. A. Relan is an employee of and stockholder in Pharming Technologies. S. Zeerleder receives research support from Viropharma. C. Drouet receives research support from GREPI and travel support from UCSD and the National Institutes of health. B. Zuraw serves as a consultant for Allan, Arrowhead, BioCryst, CSL Behring, Dyax, Ionis, Nektar, Shire and Salix; receives clinical research support from Ionis and received travel assistances from US HAEA. C. E. Hack is the founder of and a stockholder in Prothix BV.

Research paper thumbnail of Diagnosis and Treatment of Angioedema

Research paper thumbnail of Les protéases virales dans la famille des Flaviviridae

Virologie, Dec 31, 2002

La famille des Flaviviridae regroupe des virus enveloppes a ARN positif simple brin repartis dans... more La famille des Flaviviridae regroupe des virus enveloppes a ARN positif simple brin repartis dans trois genres : Flavivirus (fievre jaune, dengue, encephalites a tiques, japonaise et West Nile...), Hepacivirus (virus de l'hepatite C) et Pestivirus (virus de la diarrhee bovine). La maturation de l'unique polyproteine virale necessite l'intervention de proteases cellulaires (signalase et signal peptide peptidase) et de proteases codees par le genome viral. Ces dernieres sont au nombre de trois : 1) la protease a serine NS3pro, presente dans les trois genres de la famille virale, peut etre active avec differents cofacteurs : NS2B chez les Flavivirus, NS4A chez les Hepacivirus et les Pestivirus ; elle clive la proteine de capside et la majorite des proteines non structurales ; 2) le virus de l'hepatite C exprime par ailleurs la zinc-metalloprotease NS2-3 clivant NS2/NS3 ; 3) les pestivirus, la protease a cysteine Npro se trouvant a l'extremite N-terminale de la polyproteine. Les proteases virales sont des enzymes indispensables a la production virale lors d'un cycle infectieux et, dans une perspective therapeutique, elles representent des cibles strategiques en vue d'elaborer de nouvelles molecules antivirales.

Research paper thumbnail of Effect of Brefeldin a on Antigen-Presenting Cells

Research paper thumbnail of C1 Inhibitor as a glycoprotein: The influence of polysaccharides on its function and autoantibody target

Molecular immunology, Jan 18, 2016

C1 Inhibitor (C1Inh), a member of the Serine proteinase inhibitor family, is the most heavily gly... more C1 Inhibitor (C1Inh), a member of the Serine proteinase inhibitor family, is the most heavily glycosylated plasma protein. This work investigated the impact of C1Inh glycosylation on its function regarding protease targets and autoantibody binding. C1Inh deglycosylation was found to affect its function with O-linked polysaccharides, but not with N-linked polysaccharides, in controlling the contact phase but not C1s target, thus indicating the N-terminal domain's involvement in C1Inh function. Instructive samples demonstrated that O-deglycosylation strongly suppressed autoantibody binding, suggesting the polysaccharide motif is an antibody target. The autoantibodies did not directly affect C1Inh function.