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1. Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD

Author

Carapito, Raphael, Jung, Nicolas, Kwemou, Marius, Untrau, Meiggie, Michel, Sandra, Pichot, Angélique, Giacometti, Gaëlle, Macquin, Cécile, Ilias, Wassila, Morlon, Aurore, Kotova, Irina, Apostolova, Petya, Schmitt-Graeff, Annette, Cesbron, Anne, Gagne, Katia, Oudshoorn, Machteld, van der Holt, Bronno, Labalette, Myriam, Spierings, Eric, Picard, Christophe, Loiseau, Pascale, Tamouza, Ryad, Toubert, Antoine, Parissiadis, Anne, Dubois, Valérie, Lafarge, Xavier, Maumy-Bertrand, Myriam, Bertrand, Frédéric, Vago, Luca, Ciceri, Fabio, Paillard, Catherine, Querol, Sergi, Sierra, Jorge, Fleischhauer, Katharina, Nagler, Arnon, Labopin, Myriam, Inoko, Hidetoshi, von dem Borne, Peter A., Kuball, Jürgen, Ota, Masao, Katsuyama, Yoshihiko, Michallet, Mauricette, Lioure, Bruno, Peffault de Latour, Régis, Blaise, Didier, Cornelissen, Jan J., Yakoub-Agha, Ibrahim, Claas, Frans, Moreau, Philippe, Milpied, Noël, Charron, Dominique, Mohty, Mohamad, Zeiser, Robert, Socié, Gérard, and Bahram, Seiamak

Published
2016
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2. Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond–like features

Author

Carapito, Raphael, Konantz, Martina, Paillard, Catherine, Miao, Zhichao, Pichot, Angélique, Leduc, Magalie S., Yang, Yaping, Bergstrom, Katie L., Mahoney, Donald H., Shardy, Deborah L., Alsaleh, Ghada, Naegely, Lydie, Kolmer, Aline, Paul, Nicodème, Hanauer, Antoine, Rolli, Véronique, Müller, Joëlle S., Alghisi, Elisa, Sauteur, Loïc, Macquin, Cécile, Morlon, Aurore, Sancho, Consuelo Sebastia, Amati-Bonneau, Patrizia, Procaccio, Vincent, Mosca-Boidron, Anne-Laure, Marle, Nathalie, Osmani, Naël, Lefebvre, Olivier, Goetz, Jacky G., Unal, Sule, Akarsu, Nurten A., Radosavljevic, Mirjana, Chenard, Marie-Pierre, Rialland, Fanny, Grain, Audrey, Béné, Marie-Christine, Eveillard, Marion, Vincent, Marie, Guy, Julien, Faivre, Laurence, Thauvin-Robinet, Christel, Thevenon, Julien, Myers, Kasiani, Fleming, Mark D., Shimamura, Akiko, Bottollier-Lemallaz, Elodie, Westhof, Eric, Lengerke, Claudia, Isidor, Bertrand, and Bahram, Seiamak

Published
2017
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3. A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1β as relevant therapy for gout patients

Author

Mariotte, Alexandre, De Cauwer, Aurore, Po, Chrystelle, Abou-Faycal, Chérine, Pichot, Angélique, Paul, Nicodème, Aouadi, Ismael, Carapito, Raphael, Frisch, Benoit, Macquin, Cécile, Chatelus, Emmanuel, Sibilia, Jean, Armspach, Jean-Paul, Bahram, Seiamak, and Georgel, Philippe

Subjects
Inflammation, Mice, Knockout, Imiquimod, Gout, Administration, Topical, Injections, Subcutaneous, Interleukin-1beta, Magnetic Resonance Imaging, Antioxidants, Uric Acid, Disease Models, Animal, Mice, Adjuvants, Immunologic, Acute Disease, Animals, Cytokines, Research Paper
Abstract

Rationale: The role of Monosodium Urate (MSU) crystals in gout pathophysiology is well described, as is the major impact of IL-1β in the inflammatory reaction that constitutes the hallmark of the disease. However, despite the discovery of the NLRP3 inflammasome and its role as a Pattern Recognition Receptor linking the detection of a danger signal (MSU) to IL-1β secretion in vitro, the precise mechanisms leading to joint inflammation in gout patients are still poorly understood. Methods: Acute urate crystal inflammation was obtained by subcutaneous injections of MSU crystals in mice. Symptoms were followed by scoring, cytokine quantification by ELISA and western blot, gene expression by RT-qPCR and RNAseq; Magnetic Resonance Imaging was also used to assess inflammation. Results: We provide an extensive clinical, biological and molecular characterization of an acute uratic inflammation mouse model which accurately mimics human gout. We report the efficacy of topical imiquimod treatment and its impact on Interferon-dependent down modulation of Il-1β gene expression in this experimental model. Conclusion: Our work reveals several key features of MSU-dependent inflammation and identifies novel therapeutic opportunities for gout patients.

Published
2020

4. NLRP3- and AIM2-autonomy in a mouse model of MSU crystal-induced acute inflammation in vivo highlights imiquimod-dependent targeting of Il-1E expression as relevant therapy for gout patients

Author

Mariotte, Alexandre, De Cauwer, Aurore, Po, Chrystelle, Abou-Fayçal, Cherine, Pichot, Angélique, Paul, Nicodème, Aouadi, Ismael, Carapito, Raphael, Frisch, Benoit, Macquin, Cécile, Chatelus, Emmanuel, Sibilia, Jean, Armspach, Jean-Paul, Bahram, Seiamak, Georgel, Philippe, Frisch, Benoit, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Equipe 2 - Bases Moléculaires de la Progression des Cancers du Poumon, Inserm U823, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe Plate-forme GENOMAX (Inserm U1109), Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA)-Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie, Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de Référence pour les Maladies Systémiques Autoimmunes Rares, Rhumatologie, CHU Strasbourg, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ICube Laboratory, University of Strasbourg, CNRS, France, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

L'article est publié dans la revue sous le titre définitif :"A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1β as relevant therapy for gout patients"; International audience; The role of Monosodium Urate (MSU) crystals in gout pathophysiology is well described, as is the major impact of IL-1 in the inflammatory reaction that constitutes the hallmark of the disease. However, despite the discovery of the NLRP3 inflammasome and its role as a Pattern Recognition Receptor linking the detection of a danger signal (MSU) to IL-1 secretion in vitro, the precise mechanisms leading to joint inflammation in gout patients are still poorly understood. Here, we provide an extensive clinical, biological and molecular characterization of the acute uratic inflammation mouse model induced by subcutaneous injection of MSU crystals, which accurately mimics human gout. Our work reveals several key features of MSU-dependent inflammation and identifies novel therapeutic opportunities, among which the use of topical application of imiquimod to promote interferon-dependent anti-inflammatory action maybe relevant. All rights reserved. No reuse allowed without permission. (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

Published
2020

5. Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus-host disease in conjunction with the CMV status

Author

CDL Patiëntenzorg MI, Infection & Immunity, Cancer, Carapito, Raphael, Aouadi, Ismail, Pichot, Angélique, Spinnhirny, Perrine, Morlon, Aurore, Kotova, Irina, Macquin, Cécile, Rolli, Véronique, Cesbron, Anne, Gagne, Katia, Oudshoorn, Machteld, van der Holt, Bronno, Labalette, Myriam, Spierings, Eric, Picard, Christophe, Loiseau, Pascale, Tamouza, Ryad, Toubert, Antoine, Parissiadis, Anne, Dubois, Valérie, Paillard, Catherine, Maumy-Bertrand, Myriam, Bertrand, Frédéric, von dem Borne, Peter A, Kuball, Jürgen H E, Michallet, Mauricette, Lioure, Bruno, Peffault de Latour, Régis, Blaise, Didier, Cornelissen, Jan J, Yakoub-Agha, Ibrahim, Claas, Frans, Moreau, Philippe, Charron, Dominique, Mohty, Mohamad, Morishima, Yasuo, Socié, Gérard, Bahram, Seiamak, CDL Patiëntenzorg MI, Infection & Immunity, Cancer, Carapito, Raphael, Aouadi, Ismail, Pichot, Angélique, Spinnhirny, Perrine, Morlon, Aurore, Kotova, Irina, Macquin, Cécile, Rolli, Véronique, Cesbron, Anne, Gagne, Katia, Oudshoorn, Machteld, van der Holt, Bronno, Labalette, Myriam, Spierings, Eric, Picard, Christophe, Loiseau, Pascale, Tamouza, Ryad, Toubert, Antoine, Parissiadis, Anne, Dubois, Valérie, Paillard, Catherine, Maumy-Bertrand, Myriam, Bertrand, Frédéric, von dem Borne, Peter A, Kuball, Jürgen H E, Michallet, Mauricette, Lioure, Bruno, Peffault de Latour, Régis, Blaise, Didier, Cornelissen, Jan J, Yakoub-Agha, Ibrahim, Claas, Frans, Moreau, Philippe, Charron, Dominique, Mohty, Mohamad, Morishima, Yasuo, Socié, Gérard, and Bahram, Seiamak

Published
2020

6. Matching for the non-conventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD

Author

Carapito, Raphael, Jung, Nicolas, Kwemou, Marius, Untrau, Meiggie, Michel, Sandra, Pichot, Angélique, Giacometti, Gaëlle, Macquin, Cécile, Ilias, Wassila, Morlon, Aurore, Kotova, Irina, Apostolova, Petya, Schmitt-Graeff, Annette, Cesbron, Anne, Gagne, Katia, Oudshoorn, Machteld, van der Holt, Bronno, Labalette, Myriam, Spierings, Eric, Picard, Christophe, Loiseau, Pascale, Tamouza, Ryad, Toubert, Antoine, Parissiadis, Anne, Dubois, Valérie, Lafarge, Xavier, Maumy-Bertrand, Myriam, Bertrand, Frédéric, Vago, Luca, Ciceri, Fabio, Paillard, Catherine, Querol, Sergi, Sierra, Jorge, Fleischhauer, Katharina, Nagler, Arnon, Labopin, Myriam, Inoko, Hidetoshi, von dem Borne, Peter A, Kuball, Jürgen H E, Ota, Masao, Katsuyama, Yoshihiko, Michallet, Mauricette, Lioure, Bruno, Peffault de Latour, Régis, Blaise, Didier, Cornelissen, Jan J, Yakoub-Agha, Ibrahim, Claas, Frans, Moreau, Philippe, Milpied, Noël, Charron, Dominique, Mohty, Mohamad, Zeiser, Robert, Socié, Gérard, Bahram, Seiamak, Carapito, Raphael, Jung, Nicolas, Kwemou, Marius, Untrau, Meiggie, Michel, Sandra, Pichot, Angélique, Giacometti, Gaëlle, Macquin, Cécile, Ilias, Wassila, Morlon, Aurore, Kotova, Irina, Apostolova, Petya, Schmitt-Graeff, Annette, Cesbron, Anne, Gagne, Katia, Oudshoorn, Machteld, van der Holt, Bronno, Labalette, Myriam, Spierings, Eric, Picard, Christophe, Loiseau, Pascale, Tamouza, Ryad, Toubert, Antoine, Parissiadis, Anne, Dubois, Valérie, Lafarge, Xavier, Maumy-Bertrand, Myriam, Bertrand, Frédéric, Vago, Luca, Ciceri, Fabio, Paillard, Catherine, Querol, Sergi, Sierra, Jorge, Fleischhauer, Katharina, Nagler, Arnon, Labopin, Myriam, Inoko, Hidetoshi, von dem Borne, Peter A, Kuball, Jürgen H E, Ota, Masao, Katsuyama, Yoshihiko, Michallet, Mauricette, Lioure, Bruno, Peffault de Latour, Régis, Blaise, Didier, Cornelissen, Jan J, Yakoub-Agha, Ibrahim, Claas, Frans, Moreau, Philippe, Milpied, Noël, Charron, Dominique, Mohty, Mohamad, Zeiser, Robert, Socié, Gérard, and Bahram, Seiamak

Published
2016

7. Matching for the non-conventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD

Author

CDL Celdiagnostiek, Infection & Immunity, MS Hematologie, Regenerative Medicine and Stem Cells, Cancer, Carapito, Raphael, Jung, Nicolas, Kwemou, Marius, Untrau, Meiggie, Michel, Sandra, Pichot, Angélique, Giacometti, Gaëlle, Macquin, Cécile, Ilias, Wassila, Morlon, Aurore, Kotova, Irina, Apostolova, Petya, Schmitt-Graeff, Annette, Cesbron, Anne, Gagne, Katia, Oudshoorn, Machteld, van der Holt, Bronno, Labalette, Myriam, Spierings, Eric, Picard, Christophe, Loiseau, Pascale, Tamouza, Ryad, Toubert, Antoine, Parissiadis, Anne, Dubois, Valérie, Lafarge, Xavier, Maumy-Bertrand, Myriam, Bertrand, Frédéric, Vago, Luca, Ciceri, Fabio, Paillard, Catherine, Querol, Sergi, Sierra, Jorge, Fleischhauer, Katharina, Nagler, Arnon, Labopin, Myriam, Inoko, Hidetoshi, von dem Borne, Peter A, Kuball, Jürgen H E, Ota, Masao, Katsuyama, Yoshihiko, Michallet, Mauricette, Lioure, Bruno, Peffault de Latour, Régis, Blaise, Didier, Cornelissen, Jan J, Yakoub-Agha, Ibrahim, Claas, Frans, Moreau, Philippe, Milpied, Noël, Charron, Dominique, Mohty, Mohamad, Zeiser, Robert, Socié, Gérard, Bahram, Seiamak, CDL Celdiagnostiek, Infection & Immunity, MS Hematologie, Regenerative Medicine and Stem Cells, Cancer, Carapito, Raphael, Jung, Nicolas, Kwemou, Marius, Untrau, Meiggie, Michel, Sandra, Pichot, Angélique, Giacometti, Gaëlle, Macquin, Cécile, Ilias, Wassila, Morlon, Aurore, Kotova, Irina, Apostolova, Petya, Schmitt-Graeff, Annette, Cesbron, Anne, Gagne, Katia, Oudshoorn, Machteld, van der Holt, Bronno, Labalette, Myriam, Spierings, Eric, Picard, Christophe, Loiseau, Pascale, Tamouza, Ryad, Toubert, Antoine, Parissiadis, Anne, Dubois, Valérie, Lafarge, Xavier, Maumy-Bertrand, Myriam, Bertrand, Frédéric, Vago, Luca, Ciceri, Fabio, Paillard, Catherine, Querol, Sergi, Sierra, Jorge, Fleischhauer, Katharina, Nagler, Arnon, Labopin, Myriam, Inoko, Hidetoshi, von dem Borne, Peter A, Kuball, Jürgen H E, Ota, Masao, Katsuyama, Yoshihiko, Michallet, Mauricette, Lioure, Bruno, Peffault de Latour, Régis, Blaise, Didier, Cornelissen, Jan J, Yakoub-Agha, Ibrahim, Claas, Frans, Moreau, Philippe, Milpied, Noël, Charron, Dominique, Mohty, Mohamad, Zeiser, Robert, Socié, Gérard, and Bahram, Seiamak

Published
2016

11. Lipolysis is altered in MHC class I zinc-α2-glycoprotein deficient mice

Author

Rolli, Véronique, primary, Radosavljevic, Mirjana, additional, Astier, Valérie, additional, Macquin, Cécile, additional, Castan-Laurell, Isabelle, additional, Visentin, Virgile, additional, Guigné, Charlotte, additional, Carpéné, Christian, additional, Valet, Philippe, additional, Gilfillan, Susan, additional, and Bahram, Seiamak, additional

Published
2007
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12. Rapid Evolution of Major Histocompatibility Complex Class I Genes in Primates Generates New Disease Alleles in Humans via Hitchhiking Diversity

Author

Shiina, Takashi, primary, Ota, Masao, additional, Shimizu, Sayoko, additional, Katsuyama, Yoshihiko, additional, Hashimoto, Nami, additional, Takasu, Miwa, additional, Anzai, Tatsuya, additional, Kulski, Jerzy K, additional, Kikkawa, Eri, additional, Naruse, Taeko, additional, Kimura, Natsuki, additional, Yanagiya, Kazuyo, additional, Watanabe, Atsushi, additional, Hosomichi, Kazuyoshi, additional, Kohara, Sakae, additional, Iwamoto, Chie, additional, Umehara, Yumi, additional, Meyer, Alice, additional, Wanner, Valérie, additional, Sano, Kazumi, additional, Macquin, Cécile, additional, Ikeo, Kazuho, additional, Tokunaga, Katsushi, additional, Gojobori, Takashi, additional, Inoko, Hidetoshi, additional, and Bahram, Seiamak, additional

Published
2006
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13. Matching for the nonconventional MHC-I MICAgene significantly reduces the incidence of acute and chronic GVHD

Author

Carapito, Raphael, Jung, Nicolas, Kwemou, Marius, Untrau, Meiggie, Michel, Sandra, Pichot, Angélique, Giacometti, Gaëlle, Macquin, Cécile, Ilias, Wassila, Morlon, Aurore, Kotova, Irina, Apostolova, Petya, Schmitt-Graeff, Annette, Cesbron, Anne, Gagne, Katia, Oudshoorn, Machteld, van der Holt, Bronno, Labalette, Myriam, Spierings, Eric, Picard, Christophe, Loiseau, Pascale, Tamouza, Ryad, Toubert, Antoine, Parissiadis, Anne, Dubois, Valérie, Lafarge, Xavier, Maumy-Bertrand, Myriam, Bertrand, Frédéric, Vago, Luca, Ciceri, Fabio, Paillard, Catherine, Querol, Sergi, Sierra, Jorge, Fleischhauer, Katharina, Nagler, Arnon, Labopin, Myriam, Inoko, Hidetoshi, von dem Borne, Peter A., Kuball, Jürgen, Ota, Masao, Katsuyama, Yoshihiko, Michallet, Mauricette, Lioure, Bruno, Peffault de Latour, Régis, Blaise, Didier, Cornelissen, Jan J., Yakoub-Agha, Ibrahim, Claas, Frans, Moreau, Philippe, Milpied, Noël, Charron, Dominique, Mohty, Mohamad, Zeiser, Robert, Socié, Gérard, and Bahram, Seiamak

Abstract

Graft-versus-host disease (GVHD) is among the most challenging complications in unrelated donor hematopoietic cell transplantation (HCT). The highly polymorphic MHC class I chain–related gene A, MICA, encodes a stress-induced glycoprotein expressed primarily on epithelia. MICA interacts with the invariant activating receptor NKG2D, expressed by cytotoxic lymphocytes, and is located in the MHC, next to HLA-B. Hence, MICAhas the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICAmismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB110/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA. MICAmismatches were significantly associated with an increased incidence of grade III-IV acute GVHD (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.50-2.23; P< .001), chronic GVHD (HR, 1.50; 95% CI, 1.45-1.55; P< .001), and nonelapse mortality (HR, 1.35; 95% CI, 1.24-1.46; P< .001). The increased risk for GVHD was mirrored by a lower risk for relapse (HR, 0.50; 95% CI, 0.43-0.59; P< .001), indicating a possible graft-versus-leukemia effect. In conclusion, when possible, selecting a MICA-matched donor significantly influences key clinical outcomes of HCT in which a marked reduction of GVHD is paramount. The tight linkage disequilibrium between MICAand HLA-Brenders identifying a MICA-matched donor readily feasible in clinical practice.

Published
2016
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14. Lipolysis is altered in MHC class I zinc-α2-glycoprotein deficient mice

Author

Rolli, Véronique, Radosavljevic, Mirjana, Astier, Valérie, Macquin, Cécile, Castan-Laurell, Isabelle, Visentin, Virgile, Guigné, Charlotte, Carpéné, Christian, Valet, Philippe, Gilfillan, Susan, and Bahram, Seiamak

Subjects
MAJOR histocompatibility complex, IMMUNE system, GENOTYPE-environment interaction, TRANSPLANTATION immunology
Abstract

Abstract: Non-conventional major histocompatibility complex class I molecules are involved in a variety of physiological functions, most at the periphery of the immune system per se. Zinc-α2-glycoprotein (ZAG), the sole soluble member of this superfamily has been implicated in cachexia, a poorly understood yet life-threatening, severe wasting syndrome. To further ascertain the role of ZAG in lipid metabolism and perhaps the immune system, we inactivated both ZAG alleles by gene targeting in mice. Subjecting these ZAG deficient animals to standard or lipid rich food regimens led to increased body weight in comparison to identically treated wild-type mice. This phenotype appeared to correlate with a significant decrease in adipocytic lipolysis that could not be rescued by several pharmacological agents including β3-adrenoreceptor agonists. Furthermore, in contrast to previously reported data, ZAG was found to be ubiquitously and constitutively expressed, with an especially high level in the mouse liver. No overt immunological phenotype was identified in these animals. [Copyright &y& Elsevier]

Published
2007
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