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Author Lubka T Roumenina

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The receptor for advanced glycation end products is a sensor for cell-free heme.

Olivia May, Laure Yatime, Nicolas S Merle, Florian Delguste, Mike Howsam, Marie V Daugan, Charles Paul-Constant, Muriel Billamboz, Alina Ghinet, Steve Lancel, Jordan D Dimitrov, Eric Boulanger, Lubka T Roumenina, Marie Frimat,

Heme's interaction with Toll-like receptor 4 (TLR4) does not fully explain the proinflammatory properties of this hemoglobin-derived molecule during intravascular hemolysis. The receptor for advanced glycation end products (RAGE) shares many features with TLR4 such as common ligands and proinflammatory, prothrombotic, and pro-oxidative signaling pathways, prompting us to study its ... Read more >>

FEBS J (The FEBS journal)
[2020, :]

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Complement activation is a crucial driver of acute kidney injury in rhabdomyolysis.

Idris Boudhabhay, Victoria Poillerat, Anne Grunenwald, Carine Torset, Juliette Leon, Marie V Daugan, Francesca Lucibello, Khalil El Karoui, Amandine Ydee, Sophie Chauvet, Patrick Girardie, Steven Sacks, Conrad A Farrar, Peter Garred, Romain Berthaud, Moglie Le Quintrec, Marion Rabant, Pascale de Lonlay, Caroline Rambaud, Viviane Gnemmi, Veronique Fremeaux-Bacchi, Marie Frimat, Lubka T Roumenina,

Rhabdomyolysis is a life-threatening condition caused by skeletal muscle damage with acute kidney injury being the main complication dramatically worsening the prognosis. Specific treatment for rhabdomyolysis-induced acute kidney injury is lacking and the mechanisms of the injury are unclear. To clarify this, we studied intra-kidney complement activation (C3d and C5b-9 ... Read more >>

Kidney Int (Kidney international)
[2020, :]

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Complement System: Promoter or Suppressor of Cancer Progression?

Margot Revel, Marie V Daugan, Catherine Sautés-Fridman, Wolf H Fridman, Lubka T Roumenina,

Constituent of innate immunity, complement is present in the tumor microenvironment. The functions of complement include clearance of pathogens and maintenance of homeostasis, and as such could contribute to an anti-tumoral role in the context of certain cancers. However, multiple lines of evidence show that in many cancers, complement has ... Read more >>

Antibodies (Basel) (Antibodies (Basel, Switzerland))
[2020, 9(4):]

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The murine Microenvironment Cell Population counter method to estimate abundance of tissue-infiltrating immune and stromal cell populations in murine samples using gene expression.

Florent Petitprez, Sacha Levy, Cheng-Ming Sun, Maxime Meylan, Christophe Linhard, Etienne Becht, Nabila Elarouci, David Tavel, Lubka T Roumenina, Mira Ayadi, Catherine Sautès-Fridman, Wolf H Fridman, Aurélien de Reyniès,

Quantifying tissue-infiltrating immune and stromal cells provides clinically relevant information for various diseases. While numerous methods can quantify immune or stromal cells in human tissue samples from transcriptomic data, few are available for mouse studies. We introduce murine Microenvironment Cell Population counter (mMCP-counter), a method based on highly specific transcriptomic ... Read more >>

Genome Med (Genome medicine)
[2020, 12(1):86]

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Adult post COVID-19 multisystem inflammatory syndrome and thrombotic microangiopathy

Idris Boudhabhay, Marion Rabant, Louis-Marie Coupry, Armance Marchal, Lubka Roumenina, Khalil El-Karoui, Mehran Monchi, Franck Pourcine,

<h4>Background: </h4> The coronavirus disease 2019 pandemic has affected millions of people worldwide but medium and long-term consequences are unknown. Clinical series of Kawasaki-like multisystem inflammatory syndrome in children (MIS-C), occurring after SARS-Cov-2 spreading, have been recently described. Case presentation: We describe a case of post COVID-19 MIS in a ... Read more >>

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Plasma C3d levels as a diagnostic marker for complete complement factor I deficiency.

Leslie Naesens, Julie Smet, Simon J Tavernier, Petra Schelstraete, Levi Hoste, Stijn Lambrecht, Helene Verhelst, Jutte van der Werff Ten Bosch, Alina Ferster, Sophie Blumental, Pascale Hilbert, Tessa Kerre, Johan Vande Walle, Christoph Licht, Lubka T Roumenina, Patrick Stordeur, Filomeen Haerynck,

J Allergy Clin Immunol (The Journal of allergy and clinical immunology)
[2020, :]

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Circulating FH Protects Kidneys From Tubular Injury During Systemic Hemolysis.

Nicolas S Merle, Juliette Leon, Victoria Poillerat, Anne Grunenwald, Idris Boudhabhay, Samantha Knockaert, Tania Robe-Rybkine, Carine Torset, Matthew C Pickering, Sophie Chauvet, Veronique Fremeaux-Bacchi, Lubka T Roumenina,

Intravascular hemolysis of any cause can induce acute kidney injury (AKI). Hemolysis-derived product heme activates the innate immune complement system and contributes to renal damage. Therefore, we explored the role of the master complement regulator Factor H (FH) in the kidney's resistance to hemolysis-mediated AKI. Acute systemic hemolysis was induced ... Read more >>

Front Immunol (Frontiers in immunology)
[2020, 11:1772]

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Hemopexin as an Inhibitor of Hemolysis-Induced Complement Activation.

Victoria Poillerat, Thomas Gentinetta, Juliette Leon, Andreas Wassmer, Monika Edler, Carine Torset, Dandan Luo, Gerald Tuffin, Lubka T Roumenina,

Hemopexin is the main plasmatic scavenger of cell-free heme, released in the context of intravascular hemolysis or major cell injury. Heme is indispensable for the oxygen transport by hemoglobin but when released outside of the erythrocytes it becomes a danger-associated molecular pattern, contributing to tissue injury. One of the mechanisms ... Read more >>

Front Immunol (Frontiers in immunology)
[2020, 11:1684]

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B cells and complement at the forefront of chemotherapy.

Catherine Sautès-Fridman, Lubka T Roumenina,

Nat Rev Clin Oncol (Nature reviews. Clinical oncology)
[2020, 17(7):393-394]

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Heme induces human and mouse platelet activation through C-type-lectin-like receptor-2.

Joshua H Bourne, Martina Colicchia, Ying Di, Eleyna Martin, Alexander Slater, Lubka T Roumenina, Jordan D Dimitrov, Steve P Watson, Julie Rayes,

Haematologica (Haematologica)
[2020, :]

Cited: 2 times

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Complement activation in sickle cell disease: Dependence on cell density, hemolysis and modulation by hydroxyurea therapy.

Lubka T Roumenina, Philippe Chadebech, Gwellaouen Bodivit, Paula Vieira-Martins, Anne Grunenwald, Idris Boudhabhay, Victoria Poillerat, Sadaf Pakdaman, Laurent Kiger, Alicia Jouard, Etienne Audureau, France Pirenne, Frédéric Galactéros, Véronique Frémeaux-Bacchi, Pablo Bartolucci,

The complement system is an innate immune defense cascade that can cause tissue damage when inappropriately activated. Evidence for complement over activation has been reported in small cohorts of patients with sickle cell disease (SCD). However, the mechanism governing complement activation in SCD has not been elucidated. Here, we observe ... Read more >>

Am J Hematol (American journal of hematology)
[2020, 95(5):456-464]

Cited: 2 times

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Context-dependent roles of complement in cancer.

Lubka T Roumenina, Marie V Daugan, Florent Petitprez, Catherine Sautès-Fridman, Wolf Herman Fridman,

The tumour microenvironment (TME) highly influences the growth and spread of tumours, thus impacting the patient's clinical outcome. In this context, the complement system plays a major and complex role. It may either act to kill antibody-coated tumour cells, support local chronic inflammation or hamper antitumour T cell responses favouring ... Read more >>

Nat Rev Cancer (Nature reviews. Cancer)
[2019, 19(12):698-715]

Cited: 8 times

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The role of Complement in Post-Transfusion Hemolysis and Hyperhemolysis Reaction.

Lubka T Roumenina, Pablo Bartolucci, France Pirenne,

Transfusion-related hemolysis is classically the result of an interaction between antibodies produced by the recipient and blood group antigens carried by the donor red blood cells. This reaction may be life threatening, especially in sickle cell patients when they develop hyperhemolysis with concomitant accelerated clearance of their own red blood ... Read more >>

Transfus Med Rev (Transfusion medicine reviews)
[2019, 33(4):225-230]

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Tumor Cells Hijack Macrophage-Produced Complement C1q to Promote Tumor Growth.

Lubka T Roumenina, Marie V Daugan, Rémi Noé, Florent Petitprez, Yann A Vano, Rafaël Sanchez-Salas, Etienne Becht, Julie Meilleroux, Bénédicte Le Clec'h, Nicolas A Giraldo, Nicolas S Merle, Cheng-Ming Sun, Virginie Verkarre, Pierre Validire, Janick Selves, Laetitia Lacroix, Olivier Delfour, Isabelle Vandenberghe, Celine Thuilliez, Sonia Keddani, Imene B Sakhi, Eric Barret, Pierre Ferré, Nathalie Corvaïa, Alexandre Passioukov, Eric Chetaille, Marina Botto, Aurélien de Reynies, Stephane Marie Oudard, Arnaud Mejean, Xavier Cathelineau, Catherine Sautès-Fridman, Wolf H Fridman, Wolf H Fridman,

Clear-cell renal cell carcinoma (ccRCC) possesses an unmet medical need, particularly at the metastatic stage, when surgery is ineffective. Complement is a key factor in tissue inflammation, favoring cancer progression through the production of complement component 5a (C5a). However, the activation pathways that generate C5a in tumors remain obscure. By ... Read more >>

Cancer Immunol Res (Cancer immunology research)
[2019, 7(7):1091-1105]

Cited: 7 times

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Glomerulonephritis With Isolated C3 Deposits as a Manifestation of Subtotal Factor I Deficiency.

Idris Boudhabhay, Véronique Frémeaux-Bacchi, Lubka T Roumenina, Anissa Moktefi, Jean-Michel Goujon, Marie Matignon, Valérie Caudwell, Vincent Audard, Khalil El Karoui,

Kidney Int Rep (Kidney international reports)
[2019, 4(9):1354-1358]

Cited: 0 times

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Anti-inflammatory activity of intravenous immunoglobulin through scavenging of heme.

Marie Wiatr, Nicolas S Merle, Idris Boudhabhay, Victoria Poillerat, Sofia Rossini, Maxime Lecerf, Srini V Kaveri, Sébastian Lacroix-Desmazes, Lubka T Roumenina, Jordan D Dimitrov,

Therapeutic intravenous immunoglobulin preparations (IVIg) are used for treatment of wide range of autoimmune and inflammatory diseases. Versatile mechanisms have been reported to contribute to the immunomodulatory effects of IVIg. Here we demonstrate that IVIg has a strong potential to inhibit pro-inflammatory effect of extracellular heme. Indeed, the presence of ... Read more >>

Mol Immunol (Molecular immunology)
[2019, 111:205-208]

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P-selectin drives complement attack on endothelium during intravascular hemolysis in TLR-4/heme-dependent manner.

Nicolas S Merle, Romain Paule, Juliette Leon, Marie Daugan, Tania Robe-Rybkine, Victoria Poillerat, Carine Torset, Véronique Frémeaux-Bacchi, Jordan D Dimitrov, Lubka T Roumenina,

Hemolytic diseases are frequently linked to multiorgan failure subsequent to vascular damage. Deciphering the mechanisms leading to organ injury upon hemolytic event could bring out therapeutic approaches. Complement system activation occurs in hemolytic disorders, such as sickle cell disease, but the pathological relevance and the acquisition of a complement-activating phenotype ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2019, 116(13):6280-6285]

Cited: 13 times

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Autoantibodies Against C3b-Functional Consequences and Disease Relevance.

Vasil V Vasilev, Maria Radanova, Valentin J Lazarov, Marie-Agnes Dragon-Durey, Veronique Fremeaux-Bacchi, Lubka T Roumenina,

The complement component C3 is at the heart of the complement cascade. It is a complex protein, which generates different functional activated fragments (C3a, C3b, iC3b, C3c, C3d). C3b is a constituent of the alternative pathway C3 convertase (C3bBb), binds multiple regulators, and receptors, affecting thus the functioning of the ... Read more >>

Front Immunol (Frontiers in immunology)
[2019, 10:64]

Cited: 3 times

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Endothelium structure and function in kidney health and disease.

Noemie Jourde-Chiche, Fadi Fakhouri, Laetitia Dou, Jeremy Bellien, Stéphane Burtey, Marie Frimat, Pierre-André Jarrot, Gilles Kaplanski, Moglie Le Quintrec, Vincent Pernin, Claire Rigothier, Marion Sallée, Veronique Fremeaux-Bacchi, Dominique Guerrot, Lubka T Roumenina,

The kidney harbours different types of endothelia, each with specific structural and functional characteristics. The glomerular endothelium, which is highly fenestrated and covered by a rich glycocalyx, participates in the sieving properties of the glomerular filtration barrier and in the maintenance of podocyte structure. The microvascular endothelium in peritubular capillaries, ... Read more >>

Nat Rev Nephrol (Nature reviews. Nephrology)
[2019, 15(2):87-108]

Cited: 22 times

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Heme Drives Susceptibility of Glomerular Endothelium to Complement Overactivation Due to Inefficient Upregulation of Heme Oxygenase-1.

Olivia May, Nicolas S Merle, Anne Grunenwald, Viviane Gnemmi, Juliette Leon, Cloé Payet, Tania Robe-Rybkine, Romain Paule, Florian Delguste, Simon C Satchell, Peter W Mathieson, Marc Hazzan, Eric Boulanger, Jordan D Dimitrov, Veronique Fremeaux-Bacchi, Marie Frimat, Lubka T Roumenina,

Atypical hemolytic uremic syndrome (aHUS) is a severe disease characterized by microvascular endothelial cell (EC) lesions leading to thrombi formation, mechanical hemolysis and organ failure, predominantly renal. Complement system overactivation is a hallmark of aHUS. To investigate this selective susceptibility of the microvascular renal endothelium to complement attack and thrombotic ... Read more >>

Front Immunol (Frontiers in immunology)
[2018, 9:3008]

Cited: 7 times

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Hemolytic uremic syndrome associated with Bordetella pertussis infection in a 2-month-old infant carrying a pathogenic variant in complement factor H.

Iona Madden, Lubka T Roumenina, Hélène Langlois-Meurinne, Julie Guichoux, Brigitte Llanas, Véronique Frémeaux-Bacchi, Jérôme Harambat, Astrid Godron-Dubrasquet,

BACKGROUND:Hemolytic uremic syndrome (HUS) has been associated with a number of infectious agents. We report here the case of an infant with severe Bordetella pertussis infection who developed HUS. CASE DIAGNOSIS/TREATMENT:A 2-month-old preterm male was admitted for severe Bordetella pertussis infection. Symptoms leading to a diagnosis of hemolytic uremic syndrome ... Read more >>

Pediatr Nephrol (Pediatric nephrology (Berlin, Germany))
[2019, 34(3):533-537]

Cited: 1 time

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Detection of Autoantibodies to Complement Components by Surface Plasmon Resonance-Based Technology.

Remi Noe, Sophie Chauvet, Shambhuprasad K Togarsimalemath, Maria Chiara Marinozzi, Maria Radanova, Vasil V Vasilev, Veronique Fremeaux-Bacchi, Marie-Agnes Dragon-Durey, Lubka T Roumenina,

The innate immune complement system is a powerful defense cascade against pathogens, but can induce host tissue damage when overactivated. In pathological conditions, mainly but not restricted to renal diseases, such as lupus nephritis, atypical hemolytic uremic syndrome, and C3 glomerulopathies, complement is overactivated or dysregulated by autoantibodies directed against ... Read more >>

Methods Mol Biol (Methods in molecular biology (Clifton, N.J.))
[2019, 1901:271-280]

Cited: 1 time

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Both Monoclonal and Polyclonal Immunoglobulin Contingents Mediate Complement Activation in Monoclonal Gammopathy Associated-C3 Glomerulopathy.

Sophie Chauvet, Lubka T Roumenina, Pierre Aucouturier, Maria-Chiara Marinozzi, Marie-Agnès Dragon-Durey, Alexandre Karras, Yahsou Delmas, Moglie Le Quintrec, Dominique Guerrot, Noémie Jourde-Chiche, David Ribes, Pierre Ronco, Frank Bridoux, Véronique Fremeaux-Bacchi,

C3 glomerulopathy (C3G) results from acquired or genetic abnormalities in the complement alternative pathway (AP). C3G with monoclonal immunoglobulin (MIg-C3G) was recently included in the spectrum of "monoclonal gammopathy of renal significance." However, mechanisms of complement dysregulation in MIg-C3G are not described and the pathogenic effect of the monoclonal immunoglobulin ... Read more >>

Front Immunol (Frontiers in immunology)
[2018, 9:2260]

Cited: 3 times

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Intravascular hemolysis activates complement via cell-free heme and heme-loaded microvesicles.

Nicolas S Merle, Anne Grunenwald, Helena Rajaratnam, Viviane Gnemmi, Marie Frimat, Marie-Lucile Figueres, Samantha Knockaert, Sanah Bouzekri, Dominique Charue, Remi Noe, Tania Robe-Rybkine, Marie Le-Hoang, Nathan Brinkman, Thomas Gentinetta, Monika Edler, Sara Petrillo, Emanuela Tolosano, Sylvia Miescher, Sylvain Le Jeune, Pascal Houillier, Sophie Chauvet, Marion Rabant, Jordan D Dimitrov, Veronique Fremeaux-Bacchi, Olivier P Blanc-Brude, Lubka T Roumenina,

In hemolytic diseases, such as sickle cell disease (SCD), intravascular hemolysis results in the release of hemoglobin, heme, and heme-loaded membrane microvesicles in the bloodstream. Intravascular hemolysis is thus associated with inflammation and organ injury. Complement system can be activated by heme in vitro. We investigated the mechanisms by which ... Read more >>

JCI Insight (JCI insight)
[2018, 3(12):]

Cited: 21 times

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Complement C3 is a novel modulator of the anti-factor VIII immune response.

Julie Rayes, Mathieu Ing, Sandrine Delignat, Ivan Peyron, Laurent Gilardin, Carl-Wilhelm Vogel, David C Fritzinger, Véronique Frémeaux-Bacchi, Srinivas V Kaveri, Lubka T Roumenina, Sébastien Lacroix-Desmazes,

Development of neutralizing antibodies against therapeutic Factor VIII (FVIII) is the most serious complication of the treatment of hemophilia A. There is growing evidence to show the multifactorial origin of the anti-FVIII immune response, combining both genetic and environmental factors. While a role for the complement system on innate as ... Read more >>

Haematologica (Haematologica)
[2018, 103(2):351-360]

Cited: 3 times

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