156 results on '"Kaplanski, G."'
Search Results
2. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis
- Author
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Kyriazopoulou, E. Huet, T. Cavalli, G. Gori, A. Kyprianou, M. Pickkers, P. Eugen-Olsen, J. Clerici, M. Veas, F. Chatellier, G. Kaplanski, G. Netea, M.G. Pontali, E. Gattorno, M. Cauchois, R. Kooistra, E. Kox, M. Bandera, A. Beaussier, H. Mangioni, D. Dagna, L. van der Meer, J.W.M. Giamarellos-Bourboulis, E.J. Hayem, G. Netea, M.G. van der Meer, J.W.M. Giamarellos-Bourboulis, E.J. Volpi, S. Sormani, M.P. Signori, A. Bozzi, G. Minoia, F. Aliberti, S. Grasselli, G. Alagna, L. Lombardi, A. Ungaro, R. Agostoni, C. Blasi, F. Costantino, G. Fracanzani, A.L. Montano, N. Peyvandi, F. Sottocorno, M. Muscatello, A. Filocamo, G. Papadopoulos, A. Mouktaroudi, M. Karakike, E. Saridaki, M. Gkavogianni, T. Katrini, K. Vechlidis, N. Avgoustou, C. Chalvatzis, S. Marantos, T. Damoulari, C. Damoraki, G. Ktena, S. Tsilika, M. Koufargyris, P. Karageorgos, A. Droggiti, D.-I. Koliakou, A. Poulakou, G. Tsiakos, K. Myrodia, D.-M. Gravvani, A. Trontzas, I.P. Syrigos, K. Kalomenidis, I. Kranidioti, E. Panagopoulos, P. Petrakis, V. Metallidis, S. Loli, G. Tsachouridou, O. Dalekos, G.N. Gatselis, N. Stefos, A. Georgiadou, S. Lygoura, V. Milionis, H. Kosmidou, M. Papanikolaou, I.C. Akinosoglou, K. Giannitsioti, E. Chrysos, G. Mavroudis, P. Sidiropoulou, C. Adamis, G. Fragkou, A. Rapti, A. Alexiou, Z. Symbardi, S. Masgala, A. Kostaki, K. Kostis, E. Samarkos, M. Bakakos, P. Tzavara, V. Dimakou, K. Tzatzagou, G. Chini, M. Kotsis, V. Tsoukalas, G. Bliziotis, I. Doumas, M. Argyraki, A. Kainis, I. Fantoni, M. Cingolani, A. Angheben, A. Cardellino, C.S. Castelli, F. Serino, F.S. Nicastri, E. Ippolito, G. Bassetti, M. Selmi, C. International Collaborative Group for Anakinra in COVID-19
- Abstract
Background: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19. Methods: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491). Findings: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO2/FiO2), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20–0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO2/FiO2. In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17–0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12–0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37–1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59–3·10]). Interpretation: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L. Funding: Sobi. © 2021 Elsevier Ltd
- Published
- 2021
3. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis
- Author
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Kyriazopoulou, E., Huet, T., Cavalli, G., Gori, A., Kyprianou, M., Pickkers, P., Eugen-Olsen, J., Clerici, M., Veas, F., Chatellier, G., Kaplanski, G., Netea, M.G., Pontali, E., Gattorno, M., Cauchois, R., Kooistra, E., Kox, M., Bandera, A., Beaussier, H., Mangioni, D., Dagna, L., Meer, J.W.M. van der, Giamarellos-Bourboulis, E.J., Hayem, G., Kyriazopoulou, E., Huet, T., Cavalli, G., Gori, A., Kyprianou, M., Pickkers, P., Eugen-Olsen, J., Clerici, M., Veas, F., Chatellier, G., Kaplanski, G., Netea, M.G., Pontali, E., Gattorno, M., Cauchois, R., Kooistra, E., Kox, M., Bandera, A., Beaussier, H., Mangioni, D., Dagna, L., Meer, J.W.M. van der, Giamarellos-Bourboulis, E.J., and Hayem, G.
- Abstract
Item does not contain fulltext, BACKGROUND: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19. METHODS: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491). FINDINGS: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO(2)/FiO(2)), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [
- Published
- 2021
4. Circulating endothelial cells and progenitors as prognosis factors during auto-immune thrombotic thrombocytopenic purpura: results of a prospective multicenter french study: VB10
- Author
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Widemann, A, Pasero, C, Arnaud, L, Poullin, P, Loundou, A, Choukroun, G, Sanderson, F, Lacroix, R, Sabatier, F, Coppo, P, Dignat-George, F, and Kaplanski, G
- Published
- 2014
5. Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19
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Cauchois, R., Koubi, M., Delarbre, D., Manet, C., Carvelli, J., Blasco, V.B., Jean, R., Fouche, L., Bornet, C., Pauly, V., Mazodier, K., Pestre, V., Jarrot, P.A., Dinarello, C.A., Kaplanski, G., Cauchois, R., Koubi, M., Delarbre, D., Manet, C., Carvelli, J., Blasco, V.B., Jean, R., Fouche, L., Bornet, C., Pauly, V., Mazodier, K., Pestre, V., Jarrot, P.A., Dinarello, C.A., and Kaplanski, G.
- Abstract
Contains fulltext : 229588.pdf (Publisher’s version ) (Open Access), Around the tenth day after diagnosis, ∼20% of patients with coronavirus disease 2019 (COVID-19)-associated pneumonia evolve toward severe oxygen dependence (stage 2b) and acute respiratory distress syndrome (stage 3) associated with systemic inflammation often termed a "cytokine storm." Because interleukin-1 (IL-1) blocks the production of IL-6 and other proinflammatory cytokines, we treated COVID-19 patients early in the disease with the IL-1 receptor antagonist, anakinra. We retrospectively compared 22 patients from three different centers in France with stages 2b and 3 COVID-19-associated pneumonia presenting with acute severe respiratory failure and systemic inflammation who received either standard-of-care treatment alone (10 patients) or combined with intravenous anakinra (12 patients). Treatment started at 300 mg⋅d(-1) for 5 d, then tapered with lower dosing over 3 d. Both populations were comparable for age, comorbidities, clinical stage, and elevated biomarkers of systemic inflammation. All of the patients treated with anakinra improved clinically (P < 0.01), with no deaths, significant decreases in oxygen requirements (P < 0.05), and more days without invasive mechanical ventilation (P < 0.06), compared with the control group. The effect of anakinra was rapid, as judged by significant decrease of fever and C-reactive protein at day 3. A mean total dose of 1,950 mg was infused with no adverse side effects or bacterial infection. We conclude that early blockade of the IL-1 receptor is therapeutic in acute hyperinflammatory respiratory failure in COVID-19 patients.
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- 2020
6. Rituximab as Preventive Therapy of a Clinical Relapse in TTP With ADAMTS13 Inhibitor
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Schleinitz, N., Ebbo, M., Mazodier, K., Poullin, P., Bernit, E., Veit, V., Veyradier, A., Fakhouri, F., Kaplanski, G., and Harle, J. R.
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- 2007
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7. Infliximab in the treatment of refractory vasculitis secondary to hepatitis C-associated mixed cryoglobulinaemia
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Chandesris, M.-O., Gayet, S., Schleinitz, N., Doudier, B., Harlé, J.-Robert, and Kaplanski, G.
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- 2004
8. Increased soluble p55 and p75 tumour necrosis factor-α receptors in patients with hepatitis C-associated mixed cryoglobulinaemia
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Kaplanski, G, Marin, V, Maisonobe, T, Sbai, A, Farnarier, C, Ghillani, P, Thirion, X, Durand, J. M, Harlé, J. R, Bongrand, P, Piette, J. C, and Cacoub, P
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- 2002
9. Foscarnet-induced hypercalcaema in AIDS
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Gayet, S., Ville, E., Durand, J. M., Mars, M. E., Morange, S., Kaplanski, G., Gallais, H, and Soubeyrand, J.
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- 1997
10. Indeed, IL-18 is more than an inducer of IFN-gamma
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Dinarello, C.A., Kaplanski, G., Dinarello, C.A., and Kaplanski, G.
- Abstract
Contains fulltext : 196405.pdf (publisher's version ) (Closed access)
- Published
- 2018
11. Severe peripheral blood lymphopenia without NK cell cytotoxicty deficiency is the rule in adult acquired HLH
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Carvelli, J, primary, Piperoglou, C, additional, Vely, F, additional, Farnarier, C, additional, Mazodier, K, additional, Harle, J-R, additional, Vivier, E, additional, and Kaplanski, G, additional
- Published
- 2015
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12. Interleukin-18, more than a Th1 cytokine.
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Novick, D., Kim, S., Kaplanski, G., Dinarello, C.A., Novick, D., Kim, S., Kaplanski, G., and Dinarello, C.A.
- Abstract
Item does not contain fulltext, Together with IL-12 or IL-15, interleukin-18 (IL-18) plays a major role in the production of interferon-gamma from T-cells and natural killer cells; thus, IL-18 is considered to have a major role in the Th1 response. However, without IL-12, IL-18 is proinflammatory in an IFNgamma independent manner. IL-18 is a member of the IL-1 family of cytokines and similar to IL-1beta, the cytokine is synthesized as an inactive precursor requiring processing by caspase-1 into an active cytokine. IL-18 is also present as an integral membrane protein but requires caspase-1 for full activity in order to induce IFNgamma. Uniquely, unlike IL-1beta, the IL-18 precursor is constitutively present in nearly all cells in healthy humans and animals. The activity of IL-18 is balanced by the presence of a high-affinity, naturally occurring IL-18 binding protein (IL-18BP). In humans, increased disease severity can be associated with an imbalance of IL-18 to IL-18BP such that the levels of free IL-18 are elevated in the circulation. Increasing number of studies have expanded the role of IL-18 in mediating inflammation in animal models of disease using the IL-18BP, IL-18 deficient mice, neutralization of IL-18 or deficiency in the IL-18 receptor alpha chain. A role for IL-18 has been implicated in several autoimmune diseases, myocardial function, emphysema, metabolic syndromes, psoriasis, inflammatory bowel disease, macrophage activation syndrome, sepsis and acute kidney injury, although paradoxically, in some models of disease, IL-18 is protective. The IL-18BP has been used safely in humans and clinical trials of IL-18BP as well as neutralizing anti-IL-18 antibodies are being tested in various diseases.
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- 2013
13. Interleukin-18 and IL-18 Binding Protein
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Dinarello, C.A., Novick, D., Kim, S., Kaplanski, G., Dinarello, C.A., Novick, D., Kim, S., and Kaplanski, G.
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Contains fulltext : 125991.pdf (publisher's version ) (Open Access), Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines. Similar to IL-1beta, IL-18 is synthesized as an inactive precursor requiring processing by caspase-1 into an active cytokine but unlike IL-1beta, the IL-18 precursor is constitutively present in nearly all cells in healthy humans and animals. The activity of IL-18 is balanced by the presence of a high affinity, naturally occurring IL-18 binding protein (IL-18BP). In humans, increased disease severity can be associated with an imbalance of IL-18 to IL-18BP such that the levels of free IL-18 are elevated in the circulation. Increasing number of studies have expanded the role of IL-18 in mediating inflammation in animal models of disease using the IL-18BP, IL-18-deficient mice, neutralization of IL-18, or deficiency in the IL-18 receptor alpha chain. A role for IL-18 has been implicated in several autoimmune diseases, myocardial function, emphysema, metabolic syndromes, psoriasis, inflammatory bowel disease, hemophagocytic syndromes, macrophage activation syndrome, sepsis, and acute kidney injury, although in some models of disease, IL-18 is protective. IL-18 plays a major role in the production of interferon-gamma from T-cells and natural killer cells. The IL-18BP has been used safely in humans and clinical trials of IL-18BP as well as neutralizing anti-IL-18 antibodies are in clinical trials. This review updates the biology of IL-18 as well as its role in human disease.
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- 2013
14. Protection from inflammatory organ damage in a murine model of hemophagocytic lymphohistiocytosis using treatment with IL-18 binding protein
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Chiossone, L., Audonnet, S., Chetaille, B., Chasson, L, Farnarier, C., Berda-Haddad, Y., Jordan, S., Koszinowski, U.H., Dalod, M., Mazodier, K., Novick, D., Dinarello, C.A., Vivier, E., Kaplanski, G., Chiossone, L., Audonnet, S., Chetaille, B., Chasson, L, Farnarier, C., Berda-Haddad, Y., Jordan, S., Koszinowski, U.H., Dalod, M., Mazodier, K., Novick, D., Dinarello, C.A., Vivier, E., and Kaplanski, G.
- Abstract
Contains fulltext : 109215.pdf (publisher's version ) (Open Access), Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition due to the association of an infectious agent with lymphocyte cytotoxicity defects, either of congenital genetic origin in children or presumably acquired in adults. In HLH patients, an excess of lymphocyte or macrophage cytokines, such as IFN-gamma and TNFalpha is present in serum. In animal models of the disease, IFN-gamma and TNF-alpha have been shown to play a central pathogenic role. In humans, unusually high concentrations of IL-18, an inducer of IFN-gamma, and TNF-alpha have been reported, and are associated with an imbalance between IL-18 and its natural inhibitor IL-18 binding protein (IL-18BP) resulting in an excess of free IL-18. Here we studied whether IL-18BP could reduce disease severity in an animal model of HLH. Mouse cytomegalovirus infection in perforin-1 knock-out mice induced a lethal condition similar to human HLH characterized by cytopenia with marked inflammatory lesions in the liver and spleen as well as the presence of hemophagocytosis in bone marrow. IL-18BP treatment decreased hemophagocytosis and reversed liver as well as spleen damage. IL-18BP treatment also reduced both IFN-gamma and TNF-alpha production by CD8(+) T and NK cells, as well as Fas ligand expression on NK cell surface. These data suggest that IL-18BP is beneficial in an animal model of HLH and in combination with anti-infectious therapy may be a promising strategy to treat HLH patients.
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- 2012
15. Sterile inflammation of endothelial cell-derived apoptotic bodies is mediated by interleukin-1alpha.
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Berda-Haddad, Y., Robert, S., Salers, P., Zekraoui, L., Farnarier, C., Dinarello, C.A., Dignat-George, F., Kaplanski, G., Berda-Haddad, Y., Robert, S., Salers, P., Zekraoui, L., Farnarier, C., Dinarello, C.A., Dignat-George, F., and Kaplanski, G.
- Abstract
Item does not contain fulltext, Sterile inflammation resulting from cell death is due to the release of cell contents normally inactive and sequestered within the cell; fragments of cell membranes from dying cells also contribute to sterile inflammation. Endothelial cells undergoing stress-induced apoptosis release membrane microparticles, which become vehicles for proinflammatory signals. Here, we show that stress-activated endothelial cells release two distinct populations of particles: One population consists of membrane microparticles (<1 mum, annexin V positive without DNA and no histones) and another larger (1-3 mum) apoptotic body-like particles containing nuclear fragments and histones, representing apoptotic bodies. Contrary to present concepts, endothelial microparticles do not contain IL-1alpha and do not induce neutrophilic chemokines in vitro. In contrast, the large apoptotic bodies contain the full-length IL-1alpha precursor and the processed mature form. In vitro, these apoptotic bodies induce monocyte chemotactic protein-1 and IL-8 chemokine secretion in an IL-1alpha-dependent but IL-1beta-independent fashion. Injection of these apoptotic bodies into the peritoneal cavity of mice induces elevated serum neutrophil-inducing chemokines, which was prevented by cotreatment with the IL-1 receptor antagonist. Consistently, injection of these large apoptotic bodies into the peritoneal cavity induced a neutrophilic infiltration that was prevented by IL-1 blockade. Although apoptosis is ordinarily considered noninflammatory, these data demonstrate that nonphagocytosed endothelial apoptotic bodies are inflammatory, providing a vehicle for IL-1alpha and, therefore, constitute a unique mechanism for sterile inflammation.
- Published
- 2011
16. Pleural pseudotumoral mass revealing an extrapulmonary Pneumocystis carinii infection
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B. Granel, J. M. Durand, Kaplanski G, D. Di Stefano, and J. Soubeyrand
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Microbiology (medical) ,Adult ,Male ,Antifungal Agents ,Pleural Neoplasms ,Diagnosis, Differential ,medicine ,Humans ,Protozoal disease ,Pentamidine ,Aerosols ,biology ,AIDS-Related Opportunistic Infections ,business.industry ,Respiratory disease ,Pleural Diseases ,biology.organism_classification ,medicine.disease ,Virology ,Pneumocystis Infections ,Infectious Diseases ,Pneumocystis carinii ,Immunology ,Protozoa ,business ,Tomography, X-Ray Computed - Published
- 1996
17. IL-6, monocyte infiltration and parenchymal cells
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Bartoccioni, E., Scuderi, F., Marino, M., Provenzano, C., Kaplanski, G., Marin, V., Farnarier, C., Bartoccioni E. (ORCID:0000-0002-4434-8661), Scuderi F., Marino M. (ORCID:0000-0001-9155-6378), Provenzano C. (ORCID:0000-0001-5476-5517), Bartoccioni, E., Scuderi, F., Marino, M., Provenzano, C., Kaplanski, G., Marin, V., Farnarier, C., Bartoccioni E. (ORCID:0000-0002-4434-8661), Scuderi F., Marino M. (ORCID:0000-0001-9155-6378), and Provenzano C. (ORCID:0000-0001-5476-5517)
- Abstract
The January issue of Trends in Immunology contained an interesting article by Kaplanski et al., in which the authors observed that interleukin-6 (IL-6) acts as a switch, regulating the transition from neutrophil to monocyte involvement during the inflammatory response [1]. In this model, activated polymorphonuclear (PMN) cells release soluble interleukin-6 receptor a (sIL-6Ra), which, upon binding of locally produced IL-6, combines with glycoprotein 130 (gp130) on endothelial cells, enabling them to switch from IL-8 (neutrophil-recruiting) to monocyte chemotactic protein-1 (monocyte-recruiting) secretion
- Published
- 2003
18. Safety and efficacy of rituximab in nonviral cryoglobulinemia vasculitis: Data from the French Autoimmunity and Rituximab registry
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Terrier, B., primary, Launay, D., additional, Kaplanski, G., additional, Hot, A., additional, Larroche, C., additional, Cathébras, P., additional, Combe, B., additional, de Jaureguiberry, J. P., additional, Meyer, O., additional, Schaeverbeke, T., additional, Somogyi, A., additional, Tricot, L., additional, Zénone, T., additional, Ravaud, P., additional, Gottenberg, J. E., additional, Mariette, X., additional, and Cacoub, P., additional
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- 2010
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19. Cryoglobulinemia After Intravesical Administration of Bacille Calmette‐Guérin
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Kaplanski G, Frédérique Retornaz, J. P. Bernard, C. Roubicek, M.J. Payan, E. Cretel, J. M. Durand, and J. Soubeyrand
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Male ,Microbiology (medical) ,Mycobacterium bovis ,biology ,business.industry ,medicine.medical_treatment ,Immunotherapy ,Middle Aged ,Bacille Calmette Guerin ,biology.organism_classification ,medicine.disease ,Cryoglobulinemia ,Administration, Intravesical ,Infectious Diseases ,Urinary Bladder Neoplasms ,Immunology ,medicine ,Animals ,Humans ,business - Published
- 1998
20. Identical twins with macrophagic myofasciitis: Genetic susceptibility and triggering by aluminic vaccine adjuvants?
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Guis, S., primary, Mattei, J. P., additional, Nicoli, F., additional, Pellissier, J. F., additional, Kaplanski, G., additional, Figarella-Branger, D., additional, Manez, G. C., additional, Antipoff, G. M., additional, and Roudier, J., additional
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- 2002
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21. Increased soluble p55 and p75 tumour necrosis factor-αreceptors in patients with hepatitis C-associated mixed cryoglobulinaemia
- Author
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Kaplanski, G, primary, Marin, V, additional, Maisonobe, T, additional, Sbai, A, additional, Farnarier, C, additional, Ghillani, P, additional, Thirion, X, additional, Durand, J M, additional, Harlé, J R, additional, Bongrand, P, additional, Piette, J C, additional, and Cacoub, P, additional
- Published
- 2002
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22. Cryoglobulinemia After Intravesical Administration of Bacille Calmette‐Guérin
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Durand, J. M., primary, Roubicek, C., additional, Retornaz, F., additional, Cretel, E., additional, Payan, M. J., additional, Bernard, J. P., additional, Kaplanski, G., additional, and Soubeyrand, J., additional
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- 1998
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23. Interaction with Autologous Platelets Multiplies Interleukin-l and Tumor Necrosis Factor Production in Mononuclear Cells
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Aiura, K., primary, Clark, B. D., additional, Dinarello, C. A., additional, Margolis, N. H., additional, Kaplanski, G., additional, Burke, J. F., additional, Tompkins, R. G., additional, and Gelfand, J. A., additional
- Published
- 1997
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24. Pleural Pseudotumoral Mass Revealing an Extrapulmonary Pneumocystis carinii Infection
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Kaplanski, G., primary, Granel, B., additional, Di Stefano, D., additional, Durand, J. M., additional, and Soubeyrand, J., additional
- Published
- 1996
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25. Dapsone Therapy for Thrombocytopenia in Patients Infected with Human Immunodeficiency Virus
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Durand, J. M., primary, Lefevre, P., additional, Cretel, E., additional, Kaplanski, G., additional, and Soubeyrand, J., additional
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- 1996
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26. IL-6 and IL-8 production from cultured human endothelial cells stimulated by infection with Rickettsia conorii via a cell-associated IL-1 alpha-dependent pathway.
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Kaplanski, G, primary, Teysseire, N, additional, Farnarier, C, additional, Kaplanski, S, additional, Lissitzky, J C, additional, Durand, J M, additional, Soubeyrand, J, additional, Dinarello, C A, additional, and Bongrand, P, additional
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- 1995
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27. Interleukin-1 induces interleukin-8 secretion from endothelial cells by a juxtacrine mechanism
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Kaplanski, G, primary, Farnarier, C, additional, Kaplanski, S, additional, Porat, R, additional, Shapiro, L, additional, Bongrand, P, additional, and Dinarello, CA, additional
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- 1994
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28. A novel role for E- and P-selectins: shape control of endothelial cell monolayers
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Kaplanski, G., primary, Farnarier, C., additional, Benoliel, A.M., additional, Foa, C., additional, Kaplanski, S., additional, and Bongrand, P., additional
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- 1994
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29. Granulocyte-endothelium initial adhesion. Analysis of transient binding events mediated by E-selectin in a laminar shear flow
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Kaplanski, G., primary, Farnarier, C., additional, Tissot, O., additional, Pierres, A., additional, Benoliel, A.M., additional, Alessi, M.C., additional, Kaplanski, S., additional, and Bongrand, P., additional
- Published
- 1993
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30. Activated platelets induce endothelial secretion of interleukin-8 in vitro via an interleukin-1-mediated event
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Kaplanski, G, primary, Porat, R, additional, Aiura, K, additional, Erban, JK, additional, Gelfand, JA, additional, and Dinarello, CA, additional
- Published
- 1993
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31. Dapsone Therapy for Thrombocytopenia in Patients Infected with Human Immunodeficiency Virus
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J. Soubeyrand, E. Cretel, J. M. Durand, Lefevre P, and Kaplanski G
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Microbiology (medical) ,business.industry ,Human immunodeficiency virus (HIV) ,Gamma globulin ,Dapsone ,medicine.disease_cause ,Virology ,Infectious Diseases ,RH-antibodies ,Immunology ,medicine ,In patient ,business ,medicine.drug - Abstract
In a previous report, we compared the effectiveness of transfus ing intravenous gamma globulin and Rh antibodies into Rh-posi tive patients and found that both treatments were well tolerated [7]. Our data did not indicate that one form oftherapy was superior to the other. Nevertheless, individual responses may be quite dif ferent and may not be predicted on the basis of the effectiveness of either therapy alone. We conclude that each of these treatments can be used after failure of the other.
- Published
- 1996
32. Effect of Interferon-a2b on Cryoglobulinemia Related to Hepatitis C Virus Infection
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Durand, J. M., primary, Kaplanski, G., additional, Lefevre, P., additional, Richard, M. A., additional, Andrae, L., additional, Trepo, C., additional, and Soubeyrand, J., additional
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- 1992
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33. Interaction with autologous platelets multiplies interleukin-1 and tumor necrosis factor production in mononuclear cells.
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Aiura, K, Clark, B D, Dinarello, C A, Margolis, N H, Kaplanski, G, Burke, J F, Tompkins, R G, and Gelfand, J A
- Abstract
The effect of activated platelets on cytokine production by human peripheral blood mononuclear cells (PBMC) was investigated. When PBMC were coincubated with activated autologous platelets amid lipopolysaccharide (LPS, 50-100 pg/mL) for 8 h, the production of interleukin (IL)-1alpha increased 11- to 18-fold and tumor necrosis factor (TNF)-alpha 3- to 5-fold compared with PBMC without platelets. Activated platelets in a dual-chamber well that prevented platelet-PBMC contact but permitted passage of soluble factors enhanced IL-1alpha production (P < .01). Platelet-PBMC contact in the chamber resulted in a further enhancement of IL-1alpha production. These data suggest that platelet-PBMC interaction, both directly and with platelet-derived factors, enhances production of shock-producing IL-1alpha and TNF-alpha, albeit differently. The interaction of platelets with monocytes may play an important role in the pathophysiology of sepsis and disseminated intravascular coagulation. [ABSTRACT FROM AUTHOR]
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- 1997
34. Case report. Simultaneous occurrence of fibrillary glomerulopathy and AL amyloid.
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Dussol, B, Kaplanski, G, Daniel, L, Brunet, P, Pellissier, J-F, and Berland, Y
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Keywords:AL amyloidosis; fibrillary glomerulonephritis; IgM thrombi, Waldenstrom's macroglobulinaemia [ABSTRACT FROM PUBLISHER]
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- 1998
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35. Identical twins with macrophagic myofasciitis: Genetic susceptibility and triggering by aluminic vaccine adjuvants?
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Guis, S., Mattei, J. P., Nicoli, F., Pellissier, J. F., Kaplanski, G., Figarella-Branger, D., Manez, G. C., Antipoff, G. M., and Roudier, J.
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No abstract.
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- 2002
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36. HLA DRB101 and macrophagic myofasciitis
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Guis S, Pellissier J, Nicoli F, Reviron D, Mattei J, Gherardi R, Pelletier J, Kaplanski G, Figarella-Branger D, and jean roudier
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Meeting Abstract
37. Simultaneous occurrence of fibrillary glomerulopathy and AL amyloid.
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Dussol, B, Kaplanski, G, Daniel, L, Brunet, P, Pellissier, J F, and Berland, Y
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- 1998
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38. HLA DRB101 and macrophagic myofasciitis
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Guis, S, Pellissier, JF, Nicoli, F, Reviron, D, Mattei, JP, Gherardi, RK, Pelletier, J, Kaplanski, G, Figarella-Branger, D, and Roudier, J
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- 2003
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39. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis
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Evdoxia Kyriazopoulou, Thomas Huet, Giulio Cavalli, Andrea Gori, Miltiades Kyprianou, Peter Pickkers, Jesper Eugen-Olsen, Mario Clerici, Francisco Veas, Gilles Chatellier, Gilles Kaplanski, Mihai G Netea, Emanuele Pontali, Marco Gattorno, Raphael Cauchois, Emma Kooistra, Matthijs Kox, Alessandra Bandera, Hélène Beaussier, Davide Mangioni, Lorenzo Dagna, Jos W M van der Meer, Evangelos J Giamarellos-Bourboulis, Gilles Hayem, Mihai G. Netea, Jos W.M. van der Meer, Evangelos J. Giamarellos-Bourboulis, Stefano Volpi, Maria Pia Sormani, Alessio Signori, Giorgio Bozzi, Francesca Minoia, Stefano Aliberti, Giacomo Grasselli, Laura Alagna, Andrea Lombardi, Riccardo Ungaro, Carlo Agostoni, Francesco Blasi, Giorgio Costantino, Anna Ludovica Fracanzani, Nicola Montano, Flora Peyvandi, Marcello Sottocorno, Antonio Muscatello, Giovanni Filocamo, Antonios Papadopoulos, Maria Mouktaroudi, Eleni Karakike, Maria Saridaki, Theologia Gkavogianni, Konstantina Katrini, Nikolaos Vechlidis, Christina Avgoustou, Stamatios Chalvatzis, Theodoros Marantos, Christina Damoulari, Georgia Damoraki, Sofia Ktena, Maria Tsilika, Panagiotis Koufargyris, Athanasios Karageorgos, Dionysia-Irene Droggiti, Aikaterini Koliakou, Garyfallia Poulakou, Konstantinos Tsiakos, Dimitra-Melia Myrodia, Areti Gravvani, Ioannis P. Trontzas, Konstantinos Syrigos, Ioannis Kalomenidis, Eleftheria Kranidioti, Periklis Panagopoulos, Vasileios Petrakis, Simeon Metallidis, Georgia Loli, Olga Tsachouridou, George N. Dalekos, Nikolaos Gatselis, Aggelos Stefos, Sarah Georgiadou, Vassiliki Lygoura, Haralampos Milionis, Maria Kosmidou, Ilias C. Papanikolaou, Karolina Akinosoglou, Efthymia Giannitsioti, Georgios Chrysos, Panagiotis Mavroudis, Chrysanthi Sidiropoulou, Georgios Adamis, Archontoula Fragkou, Aggeliki Rapti, Zoi Alexiou, Styliani Symbardi, Aikaterini Masgala, Konstantina Kostaki, Evangelos Kostis, Michael Samarkos, Petros Bakakos, Vassiliki Tzavara, Katerina Dimakou, Glykeria Tzatzagou, Maria Chini, Vasileios Kotsis, George Tsoukalas, Ioannis Bliziotis, Michael Doumas, Aikaterini Argyraki, Ilias Kainis, Massimo Fantoni, Antonella Cingolani, Andrea Angheben, Chiara Simona Cardellino, Francesco Castelli, Francesco Saverio Serino, Emanuele Nicastri, Giuseppe Ippolito, Matteo Bassetti, Carlo Selmi, 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), Kyriazopoulou, E., Huet, T., Cavalli, Giulio., Gori, A., Kyprianou, M., Pickkers, P., Eugen-Olsen, J., Clerici, M., Veas, F., Chatellier, G., Kaplanski, G., Netea, M. G., Pontali, E., Gattorno, M., Cauchois, R., Kooistra, E., Kox, M., Bandera, A., Beaussier, H., Mangioni, D., Dagna, L., van der Meer, J. W. M., Giamarellos-Bourboulis, E. J., Hayem, G., Volpi, S., Sormani, M. P., Signori, A., Bozzi, G., Minoia, F., Aliberti, S., Grasselli, G., Alagna, L., Lombardi, A., Ungaro, R., Agostoni, C., Blasi, F., Costantino, G., Fracanzani, A. L., Montano, N., Peyvandi, F., Sottocorno, M., Muscatello, A., Filocamo, G., Papadopoulos, A., Mouktaroudi, M., Karakike, E., Saridaki, M., Gkavogianni, T., Katrini, K., Vechlidis, N., Avgoustou, C., Chalvatzis, S., Marantos, T., Damoulari, C., Damoraki, G., Ktena, S., Tsilika, M., Koufargyris, P., Karageorgos, A., Droggiti, D. -I., Koliakou, A., Poulakou, G., Tsiakos, K., Myrodia, D. -M., Gravvani, A., Trontzas, I. P., Syrigos, K., Kalomenidis, I., Kranidioti, E., Panagopoulos, P., Petrakis, V., Metallidis, S., Loli, G., Tsachouridou, O., Dalekos, G. N., Gatselis, N., Stefos, A., Georgiadou, S., Lygoura, V., Milionis, H., Kosmidou, M., Papanikolaou, I. C., Akinosoglou, K., Giannitsioti, E., Chrysos, G., Mavroudis, P., Sidiropoulou, C., Adamis, G., Fragkou, A., Rapti, A., Alexiou, Z., Symbardi, S., Masgala, A., Kostaki, K., Kostis, E., Samarkos, M., Bakakos, P., Tzavara, V., Dimakou, K., Tzatzagou, G., Chini, M., Kotsis, V., Tsoukalas, G., Bliziotis, I., Doumas, M., Argyraki, A., Kainis, I., Fantoni, M., Cingolani, A., Angheben, A., Cardellino, C. S., Castelli, F., Serino, F. S., Nicastri, E., Ippolito, G., Bassetti, M., and Selmi, C.
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medicine.medical_specialty ,Anakinra ,business.industry ,Secondary infection ,[SDV]Life Sciences [q-bio] ,Immunology ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Odds ratio ,Articles ,Placebo ,law.invention ,Rheumatology ,Randomized controlled trial ,law ,Meta-analysis ,Fraction of inspired oxygen ,Internal medicine ,Clinical endpoint ,Immunology and Allergy ,Medicine ,business ,ComputingMilieux_MISCELLANEOUS ,medicine.drug - Abstract
Contains fulltext : 237989.pdf (Publisher’s version ) (Closed access) BACKGROUND: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19. METHODS: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491). FINDINGS: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO(2)/FiO(2)), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20-0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO(2)/FiO(2). In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17-0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12-0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37-1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59-3·10]). INTERPRETATION: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L. FUNDING: Sobi.
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- 2021
40. Vascular endothelial-cadherin is involved in endothelial cell detachment during thrombotic thrombocytopenic purpura.
- Author
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Cauchois R, Lagarde M, Muller R, Faccini J, Leroyer A, Arnaud L, Poullin P, Dignat-George F, Kaplanski G, and Tellier E
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- Humans, Animals, Phosphorylation, Male, Middle Aged, Female, Case-Control Studies, Adult, Calcium metabolism, Calcium blood, Endothelial Cells metabolism, ADAMTS13 Protein blood, ADAMTS13 Protein metabolism, Cells, Cultured, Mice, Mice, Inbred C57BL, Severity of Illness Index, Aged, Cadherins metabolism, Purpura, Thrombotic Thrombocytopenic blood, Human Umbilical Vein Endothelial Cells metabolism, Antigens, CD metabolism, Capillary Permeability, Cell Adhesion
- Abstract
Background: Immune thrombotic thrombocytopenic purpura (i-TTP) is a life-threatening thrombotic microangiopathy linked to ADAMTS-13 deficiency. It has long been assumed that the activation of endothelial cells is the triggering factor for the thrombotic thrombocytopenic purpura crisis. Circulating endothelial cells (CECs) have been shown to be a biomarker of vascular damage and are associated with the clinical severity of i-TTP. However, the mechanisms leading to endothelial cell detachment remain unclear., Objectives: We investigated junctional destabilization the mechanisms underlying cell detachment in thrombotic thrombocytopenic purpura., Methods: We quantified CECs in i-TTP patients and investigated the effect of plasmas in vitro by measuring phosphorylation and internalization of vascular endothelial (VE)-Cadherin and in vivo in a vascular permeability model., Results: In plasma from i-TTP patients, we show that CEC count is associated with severity and correlated to intracellular calcium influx (P < .01). In vitro, serum from i-TTP patients induced stronger detachment of human umbilical vein endothelial cells than serum from control patients (P < .001). Plasma from i-TTP patients induced a higher calcium-dependent phosphorylation (P < .05) and internalization (P < .05) of VE-cadherin compared with plasma from control patients. This effect could be reproduced by immunoglobulin (Ig)G fraction isolated from patient plasma and, in particular, by the F(ab)'2 fragments of the corresponding IgG. In addition, subcutaneous injection of i-TTP plasma into mice resulted in higher vascular permeability than plasma from control patients. An inhibitor of endothelial calcium influx, ITF1697, normalized this increase in permeability., Conclusion: Our results suggest that plasma-induced endothelial activation also leads to an increase in vascular permeability. They contribute to the understanding of the mechanisms behind the presence of elevated CECs in patients' blood by linking endothelial activation to endothelial injury., Competing Interests: Declaration of competing interests P.P. is a member of the scientific advisory boards of Ablynx-Sanofi. The other authors declare no competing financial interests., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)
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- 2024
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41. Polymyalgia rheumatica and giant cell arteritis following COVID-19 vaccination: Results from a nationwide survey.
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Jarrot PA, Mirouse A, Ottaviani S, Cadiou S, Salmon JH, Liozon E, Parreau S, Michaud M, Terrier B, Gavand PE, Trefond L, Lavoiepierre V, Keraen J, Rekassa D, Bouldoires B, Weitten T, Roche D, Poulet A, Charpin C, Grobost V, Hermet M, Pallure M, Wackenheim C, Karkowski L, Grumet P, Rogier T, Belkefi N, Pestre V, Broquet E, Leurs A, Gautier S, Gras V, Gilet P, Holubar J, Sivova N, Schleinitz N, Durand JM, Castel B, Petrier A, Arcani R, Gramont B, Guilpain P, Lepidi H, Weiller PJ, Micallef J, Saadoun D, and Kaplanski G
- Subjects
- Adult, Humans, Middle Aged, COVID-19 Vaccines adverse effects, Ad26COVS1, BNT162 Vaccine, ChAdOx1 nCoV-19, Vaccination adverse effects, Giant Cell Arteritis epidemiology, Polymyalgia Rheumatica epidemiology, COVID-19 epidemiology, COVID-19 prevention & control
- Abstract
We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.
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- 2024
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42. Diagnosis of thrombotic thrombocytopenic purpura: easy-to-use fiber optic surface plasmon resonance immunoassays for automated ADAMTS-13 antigen and conformation evaluation.
- Author
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Bonnez Q, Dekimpe C, Bekaert T, Tellier E, Kaplanski G, Joly BS, Veyradier A, Coppo P, Lammertyn J, Tersteeg C, De Meyer SF, and Vanhoorelbeke K
- Subjects
- Humans, Case-Control Studies, Biomarkers blood, Reproducibility of Results, Protein Conformation, Predictive Value of Tests, Immunoassay methods, Automation, Laboratory, Female, Male, ADAMTS13 Protein blood, ADAMTS13 Protein immunology, Purpura, Thrombotic Thrombocytopenic diagnosis, Purpura, Thrombotic Thrombocytopenic blood, Purpura, Thrombotic Thrombocytopenic immunology, Surface Plasmon Resonance, Enzyme-Linked Immunosorbent Assay methods
- Abstract
Background: Laboratory diagnosis of immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains challenging when ADAMTS-13 activity ranges between 10% and 20%. To prevent misdiagnosis, open ADAMTS-13 conformation gained clinical attention as a novel biomarker, especially to diagnose acute iTTP in patients with diagnostic undecisive ADAMTS-13 activity. Plasma ADAMTS-13 conformation analysis corrects for ADAMTS-13 antigen, with both parameters being characterized in enzyme-linked immunosorbent assay (ELISA)-based reference assays requiring expert technicians., Objectives: To design ADAMTS-13 antigen and conformation assays on automated, easy-to-use fiber optic surface plasmon resonance (FO-SPR) technology to promote assay accessibility and diagnose challenging iTTP patients., Methods: ADAMTS-13 antigen and conformation assays were designed on FO-SPR technology. Plasma of 20 healthy donors and 20 acute iTTP patients were quantified, and data from FO-SPR and ELISA reference assays were compared., Results: Following assay design, both antigen and conformation FO-SPR assays were optimized and characterized, presenting strong analytical sensitivity (detection limit of 0.001 μg/mL) and repeatability (interassay variation of 14.4%). Comparative analysis suggested positive correlation (Spearman r of 0.92) and good agreement between FO-SPR and ELISA assays. As expected, FO-SPR assays showed a closed or open ADAMTS-13 conformation in healthy donors and acute iTTP patients, respectively., Conclusion: Both ADAMTS-13 antigen and conformation assays were transferred onto automated, easy-to-use FO-SPR technology, displaying potent analytical sensitivity and reproducibility. ADAMTS-13 antigen and conformation were determined for healthy donors and acute iTTP patients showing strong correlation with ELISA reference. Introducing FO-SPR technology in clinical context could support routine diagnosis of acute iTTP patients, notably when ADAMTS-13 activity fluctuates between 10% and 20%., Competing Interests: Declaration of competing interests J.L. is a member of the Board of Directors of FOx Biosystems. Q.B., C.D., T.B., E.T., G.K., B.S.J., A.V., P.C., C.T., S.F.D.M., and K.V. have no conflicts of interest to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)
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- 2024
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43. Macrophage IL-1β-positive microvesicles exhibit thrombo-inflammatory properties and are detectable in patients with active juvenile idiopathic arthritis.
- Author
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Cambon A, Rebelle C, Bachelier R, Arnaud L, Robert S, Lagarde M, Muller R, Tellier E, Kara Y, Leroyer A, Farnarier C, Vallier L, Chareyre C, Retornaz K, Jurquet AL, Tran TA, Lacroix R, Dignat-George F, and Kaplanski G
- Subjects
- Humans, Animals, Mice, Inflammasomes metabolism, Lipopolysaccharides pharmacology, Receptors, Purinergic P2X7 metabolism, Macrophages metabolism, Caspase 1 metabolism, Adenosine Triphosphate metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Arthritis, Juvenile metabolism
- Abstract
Objective: IL-1β is a leaderless cytokine with poorly known secretory mechanisms that is barely detectable in serum of patients, including those with an IL-1β-mediated disease such as systemic juvenile idiopathic arthritis (sJIA). Leukocyte microvesicles (MVs) may be a mechanism of IL-1β secretion. The first objective of our study was to characterize IL-1β-positive MVs obtained from macrophage cell culture supernatants and to investigate their biological functions in vitro and in vivo . The second objective was to detect circulating IL-1β-positive MVs in JIA patients., Methods: MVs were purified by serial centrifugations from PBMCs, or THP-1 differentiated into macrophages, then stimulated with LPS ± ATP. MV content was analyzed for the presence of IL-1β, NLRP3 inflammasome, caspase-1, P2X7 receptor, and tissue factor (TF) using ELISA, Western blot, or flow cytometry. MV biological properties were studied in vitro by measuring VCAM-1, ICAM-1, and E-selectin expression after HUVEC co-culture and factor-Xa generation test was realized. In vivo , MVs' ability to recruit leukocytes in a murine model of peritonitis was evaluated. Plasmatic IL-1β-positive MVs were studied ex vivo in 10 active JIA patients using flow cytometry., Results: THP-1-derived macrophages stimulated with LPS and ATP released MVs, which contained NLRP3, caspase-1, and the 33-kDa precursor and 17-kDa mature forms of IL-1β and bioactive TF. IL-1β-positive MVs expressed P2X7 receptor and released soluble IL-1β in response to ATP stimulation in vitro . In mice, MVs induced a leukocyte peritoneal infiltrate, which was reduced by treatment with the IL-1 receptor antagonist. Finally, IL-1β-positive MVs were detectable in plasma from 10 active JIA patients., Conclusion: MVs shed from activated macrophages contain IL-1β, NLRP3 inflammasome components, and TF, and constitute thrombo-inflammatory vectors that can be detected in the plasma from active JIA patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cambon, Rebelle, Bachelier, Arnaud, Robert, Lagarde, Muller, Tellier, Kara, Leroyer, Farnarier, Vallier, Chareyre, Retornaz, Jurquet, Tran, Lacroix, Dignat-George and Kaplanski.)
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- 2023
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44. NLRP3 inflammasome and interleukin-1 contributions to COVID-19-associated coagulopathy and immunothrombosis.
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Potere N, Garrad E, Kanthi Y, Di Nisio M, Kaplanski G, Bonaventura A, Connors JM, De Caterina R, and Abbate A
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- Humans, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Thromboinflammation, Interleukin-1beta metabolism, Inflammation, Inflammasomes metabolism, COVID-19
- Abstract
Immunothrombosis-immune-mediated activation of coagulation-is protective against pathogens, but excessive immunothrombosis can result in pathological thrombosis and multiorgan damage, as in severe coronavirus disease 2019 (COVID-19). The NACHT-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome produces major proinflammatory cytokines of the interleukin (IL)-1 family, IL-1β and IL-18, and induces pyroptotic cell death. Activation of the NLRP3 inflammasome pathway also promotes immunothrombotic programs including release of neutrophil extracellular traps and tissue factor by leukocytes, and prothrombotic responses by platelets and the vascular endothelium. NLRP3 inflammasome activation occurs in patients with COVID-19 pneumonia. In preclinical models, NLRP3 inflammasome pathway blockade restrains COVID-19-like hyperinflammation and pathology. Anakinra, recombinant human IL-1 receptor antagonist, showed safety and efficacy and is approved for the treatment of hypoxaemic COVID-19 patients with early signs of hyperinflammation. The non-selective NLRP3 inhibitor colchicine reduced hospitalization and death in a subgroup of COVID-19 outpatients but is not approved for the treatment of COVID-19. Additional COVID-19 trials testing NLRP3 inflammasome pathway blockers are inconclusive or ongoing. We herein outline the contribution of immunothrombosis to COVID-19-associated coagulopathy, and review preclinical and clinical evidence suggesting an engagement of the NLRP3 inflammasome pathway in the immunothrombotic pathogenesis of COVID-19. We also summarize current efforts to target the NLRP3 inflammasome pathway in COVID-19, and discuss challenges, unmet gaps, and the therapeutic potential that inflammasome-targeted strategies may provide for inflammation-driven thrombotic disorders including COVID-19., Competing Interests: Conflict of interest: N.P. has received a training fellowship from the International Society on Thrombosis and Haemostasis and research funding from the International Network of VENous Thromboembolism Clinical Research Networks (INVENT), outside of the present work. Y.K. is an inventor on a patent application (US20180369278A1) by the University of Michigan on the use of biogases in vascular disease. M.D.N. reports personal fees as an invited speaker from Bayer, Daiichi Sankyo, and Viatris, personal fees for advisory board membership from LEO Pharma and Pfizer, and institutional funding from LEO Pharma. G.K. has received honorary fees from Swedish Orphan Biovitrum, Chugai-Roche, and Amgen. A.B. received a travel grant from Kiniksa Pharmaceuticals Ltd to attend the 2019 AHA Scientific Sessions and honoraria from Effetti s.r.l. (Milan, Italy) to collaborate on the medical website http://www.inflammology.org, outside the present work. J.M.C. has received personal fees for scientific advisory boards and consulting from Abbott, Anthos, Alnylam, Bristol Myers Squibb, Five Prime Therapeutics, Pfizer, Takeda, and research funding from CSL Behring, outside of the submitted work. R.D.C. has received personal fees from Boehringer-Ingelheim, Bayer, BMS-Pfizer, Daiichi Sankyo, Novartis, Roche, Sanofi, Amgen, Milestone, Menarini, AstraZeneca, and Guidotti, outside the submitted work. A.A. has received research grant funding and has served as a paid scientific advisor to Implicit Biosciences, Kiniksa, Lilly, Merck, Novartis, Novo Nordisk, Olatec, R-Pharm, Serpin Pharma, and Swedish Orphan Biovitrum, outside of the submitted work. E.G. has nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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45. Measuring ADAMTS-13 activity to diagnose thrombotic thrombocytopenic purpura: a novel, fast fiber-optic surface plasmon resonance immunoassay.
- Author
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Bonnez Q, Dekimpe C, Tellier E, Kaplanski G, Verhamme P, Tersteeg C, De Meyer SF, Lammertyn J, Joly B, Coppo P, Veyradier A, and Vanhoorelbeke K
- Abstract
Background: Thrombotic thrombocytopenic purpura (TTP) is characterized by severe ADAMTS-13 activity deficiency (<10%). Diagnostic testing is challenging because of unavailability, high cost, and expert technician requirement of ADAMTS-13 enzyme assays. Cost-effective, automated fiber-optic surface plasmon resonance (FO-SPR) platforms show potential for developing diagnostic tests. Yet, FO-SPR has never been explored to measure enzymatic activities., Objectives: To develop an easy-to-use ADAMTS-13 activity assay utilizing optical fibers to rapidly diagnose TTP., Methods: The ADAMTS-13 activity assay was designed and optimized using FO-SPR technology based on a previously described enzyme-linked immunosorbent assay setup. A calibration curve was generated to quantify ADAMTS-13 activity in plasma of healthy donors and patients with acute immune-mediated TTP (iTTP), hemolytic uremic syndrome, or sepsis. ADAMTS-13 activity data from FO-SPR and fluorescence resonance energy transfer-based strategies (FRETS)-VWF73 reference assays were compared., Results: After initial assay development, optimization improved read-out magnitude and signal-to-noise ratio and reduced variation. Further characterization demonstrated a detection limit (6.8%) and inter-assay variation (Coefficient of variation, 7.2%) that showed good analytical sensitivity and repeatability. From diverse plasma samples, only plasma from patients with acute iTTP showed ADAMTS-13 activities below 10%. Strong Pearson correlation ( r = 0.854) between FO-SPR and reference FRETS-VWF73 assays were observed for all measured samples., Conclusions: A fast ADAMTS-13 activity assay was designed onto automated FO-SPR technology. Optimization resulted in sensitive ADAMTS-13 activity measurements with a detection limit enabling clinical diagnosis of TTP within 3 hours. The FO-SPR assay proved strong correlation with the reference FRETS-VWF73 assay. For the first time, this assay demonstrated the capacity of FO-SPR technology to measure enzymatic activity in pre-clinical context., (© 2023 The Author(s).)
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- 2023
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46. Anti-Jo-1 autoantibodies: biomarkers of severity and evolution of the disease in antisynthetase syndrome.
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Arcani R, Rey L, Mazziotto A, Bertin D, Kaplanski G, Jarrot PA, Lafforgue P, Venton G, Heim X, Villani P, Mège JL, Brodovitch A, and Bardin N
- Subjects
- Humans, Biomarkers, Retrospective Studies, Autoantibodies, Myositis
- Abstract
Background: Anti-Jo-1 autoantibodies represent essential markers in the diagnosis of antisynthetase syndrome (ASS). In this retrospective study, we aimed to investigate whether their concentrations and fluctuations could both respectively reflect the severity and evolution of ASS., Methods: Between 2015 and 2020, clinical and biological features of ASS patients with at least one positive measure of anti-Jo-1 autoantibody were collected. At each serum sampling, we assessed myositis activity by using the Myositis Intention to Treat Activities Index (MITAX) and compared anti-Jo-1 concentrations with ASS severity, anti-Jo-1 concentrations between patients with and without active disease, and changes in anti-Jo-1 concentrations with disease activity., Results: Forty-eight patients with ASS had at least one positive determination of anti-Jo-1 concentration. Among them, twenty-nine patients had at least two determinations of anti-Jo-1 autoantibody in their follow-up. We showed that these autoantibody concentrations were significantly correlated with MITAX (r = 0.4, p = 0.03) and creatine kinase concentration (r = 0.34, p = 0.002) and that they were significantly higher in patients with active disease than in those with inactive disease (91.7 IU/L vs 44.4 IU/L, p = 0.016). During follow-up, we found a significant correlation between fluctuations of anti-Jo-1 autoantibody concentrations and MITAX score (r = 0.7, p < 0.0001)., Conclusion: Our results suggest that anti-Jo-1 autoantibody concentration could be a predictive marker of the severity and evolution of ASS and show that their quantification could represent a precious tool for disease monitoring and for improving the therapeutic management of ASS patients., (© 2023. The Author(s).)
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- 2023
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47. Tocilizumab versus anakinra in COVID-19: results from propensity score matching.
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Arcani R, Correard F, Suchon P, Kaplanski G, Jean R, Cauchois R, Leprince M, Arcani V, Seguier J, De Sainte Marie B, Andre B, Koubi M, Rossi P, Gayet S, Gobin N, Garrido V, Weiland J, Jouve E, Couderc AL, Villani P, and Daumas A
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- Humans, Male, Aged, SARS-CoV-2, Interleukin 1 Receptor Antagonist Protein therapeutic use, Propensity Score, Retrospective Studies, COVID-19 Drug Treatment, Oxygen, COVID-19
- Abstract
Background: Tocilizumab and anakinra are anti-interleukin drugs to treat severe coronavirus disease 2019 (COVID-19) refractory to corticosteroids. However, no studies compared the efficacy of tocilizumab versus anakinra to guide the choice of the therapy in clinical practice. We aimed to compare the outcomes of COVID-19 patients treated with tocilizumab or anakinra., Methods: Our retrospective study was conducted in three French university hospitals between February 2021 and February 2022 and included all the consecutive hospitalized patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection assessed by RT-PCR who were treated with tocilizumab or anakinra. A propensity score matching was performed to minimize confounding effects due to the non-random allocation., Results: Among 235 patients (mean age, 72 years; 60.9% of male patients), the 28-day mortality (29.4% vs. 31.2%, p = 0.76), the in-hospital mortality (31.7% vs. 33.0%, p = 0.83), the high-flow oxygen requirement (17.5% vs. 18.3%, p = 0.86), the intensive care unit admission rate (30.8% vs. 22.2%, p = 0.30), and the mechanical ventilation rate (15.4% vs. 11.1%, p = 0.50) were similar in patients receiving tocilizumab and those receiving anakinra. After propensity score matching, the 28-day mortality (29.1% vs. 30.4%, p = 1) and the rate of high-flow oxygen requirement (10.1% vs. 21.5%, p = 0.081) did not differ between patients receiving tocilizumab or anakinra. Secondary infection rates were similar between the tocilizumab and anakinra groups (6.3% vs. 9.2%, p = 0.44)., Conclusion: Our study showed comparable efficacy and safety profiles of tocilizumab and anakinra to treat severe COVID-19., Competing Interests: GK has received from ROCHE-CHUGAI Research Grants <€20,000 and fees from Sobi France for scientific presentations <€4,000 and participated in a SOBI Advisory Board on COVID unpaid and an OLATEC Monitoring Board unpaid. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Arcani, Correard, Suchon, Kaplanski, Jean, Cauchois, Leprince, Arcani, Seguier, De Sainte Marie, Andre, Koubi, Rossi, Gayet, Gobin, Garrido, Weiland, Jouve, Couderc, Villani and Daumas.)
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- 2023
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48. Immune-mediated thrombotic thrombocytopenic purpura plasma induces calcium- and IgG-dependent endothelial activation: correlations with disease severity.
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Tellier E, Widemann A, Cauchois R, Faccini J, Lagarde M, Brun M, Robert P, Robert S, Bachelier R, Poullin P, Roose E, Vanhoorelbeke K, Coppo P, Dignat-George F, and Kaplanski G
- Subjects
- Animals, Humans, Calcium, von Willebrand Factor metabolism, Immunoglobulin G, ADAMTS13 Protein, Patient Acuity, Purpura, Thrombotic Thrombocytopenic
- Abstract
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by a severe ADAMTS13 deficiency due to the presence of anti-ADAMTS13 auto-antibodies, with subsequent accumulation of circulating ultra-large von Willebrand factor (VWF) multimers. The role of endothelial cell activation as a trigger of the disease has been suggested in animal models but remains to be demonstrated in humans. We prospectively obtained plasma from the first plasma exchange of 25 patients during iTTP acute phase. iTTP but not control plasma, induced a rapid VWF release and P-selectin exposure on the surface of dermal human micro-vascular endothelial cell (HMVEC-d), associated with angiopoietin-2 and endothelin-1 secretion, consistent with Weibel-Palade bodies exocytosis. Calcium (Ca2+) blockade significantly decreased VWF release, whereas iTTP plasma induced a rapid and sustained Ca2+ flux in HMVEC-d which correlated in retrospect, with disease severity and survival in 62 iTTP patients. F(ab)'2 fragments purified from the immunoglobulin G fraction of iTTP plasma mainly induced endothelial cell activation with additional minor roles for circulating free heme and nucleosomes, but not for complement. Furthermore, two anti-ADAMTS13 monoclonal antibodies purified from iTTP patients' B cells, but not serum from hereditary TTP, induced endothelial Ca2+ flux associated with Weibel-Palade bodies exocytosis in vitro, whereas inhibition of endothelial ADAMTS13 expression using small intering RNA, significantly decreased the stimulating effects of iTTP immunoglobulin G. In conclusion, Ca2+-mediated endothelial cell activation constitutes a "second hit" of iTTP, is correlated with the severity of the disease and may constitute a possible therapeutic target.
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- 2023
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49. BIOMARKERS: CAN THEY REALLY GUIDE OUR DAILY PRACTICE?
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Tsangaris I, Antonakos N, Fantoni M, Kaplanski G, Kyriazopoulou E, Veas F, and Clemens M
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- Humans, Biomarkers, Ferritins, Procalcitonin, C-Reactive Protein, Bacteremia
- Abstract
Abstract: Optimal management of septic patients requires accurate assessment of both current severity status and prognosis. Since the 1990s, substantial advances have been made in the use of circulating biomarkers for such assessments. This summary of the session on "Biomarkers: can they really use guide our daily practice?" presented at the 2021 WEB-CONFERENCE OF THE EUROPEAN SHOCK SOCIETY, 6 November 2021. These biomarkers include ultrasensitive detection of bacteremia, circulating soluble urokina-type plasminogen activator receptor (suPAR), C-reactive protein (CRP) and ferritin and procalcitonin. In addition, the potential application of novel multiwavelength optical biosensor technology allows noninvasive monitoring of multiple metabolites that can be used to assess severity and prognosis in septic patients. The application these biomarkers and improved technologies provide the potential for improved personalized management of septic patients., Competing Interests: M.F. served as advisor for SOBI and Menarini and as both advisor and speaker for GSK. F.V. is cofounder and Chie Scientific Officer of ApoH-Technologies; He acknowledges ApoH-Technologies’ team as well as the European Commission for the European Projects: EDCTP “PANDORA-ID-NET” (grant no. RIA2016E-1609) and Horizon Europe “EPIC-Crown 2” (grant no. 101046084). The rest of the authors report no conflict of interests., (Copyright © 2023 by the Shock Society.)
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- 2023
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50. Is Endothelial Activation a Critical Event in Thrombotic Thrombocytopenic Purpura?
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Cauchois R, Muller R, Lagarde M, Dignat-George F, Tellier E, and Kaplanski G
- Abstract
Thrombotic thrombocytopenic purpura (TTP) is a severe thrombotic microangiopathy. The current pathophysiologic paradigm suggests that the ADAMTS13 deficiency leads to Ultra Large-Von Willebrand Factor multimers accumulation with generation of disseminated microthrombi. Nevertheless, the role of endothelial cells in this pathology remains an issue. In this review, we discuss the various clinical, in vitro and in vivo experimental data that support the important role of the endothelium in this pathology, suggesting that ADAMTS13 deficiency may be a necessary but not sufficient condition to induce TTP. The "second hit" model suggests that in TTP, in addition to ADAMTS13 deficiency, endogenous or exogenous factors induce endothelial activation affecting mainly microvascular cells. This leads to Weibel-Palade bodies degranulation, resulting in UL-VWF accumulation in microcirculation. This endothelial activation seems to be worsened by various amplification loops, such as the complement system, nucleosomes and free heme.
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- 2023
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