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1. The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation

Author

Carapito, Raphael, Aouadi, Ismail, Verniquet, Martin, Untrau, Meiggie, Pichot, Angélique, Beaudrey, Thomas, Bassand, Xavier, Meyer, Sébastien, Faucher, Loic, Posson, Juliane, Morlon, Aurore, Kotova, Irina, Delbos, Florent, Walencik, Alexandre, Aarnink, Alice, Kennel, Anne, Suberbielle, Caroline, Taupin, Jean-Luc, Matern, Benedict M., Spierings, Eric, Congy-Jolivet, Nicolas, Essaydi, Arnaud, Perrin, Peggy, Blancher, Antoine, Charron, Dominique, Cereb, Nezih, Maumy-Bertrand, Myriam, Bertrand, Frédéric, Garrigue, Valérie, Pernin, Vincent, Weekers, Laurent, Naesens, Maarten, Kamar, Nassim, Legendre, Christophe, Glotz, Denis, Caillard, Sophie, Ladrière, Marc, Giral, Magali, Anglicheau, Dany, Süsal, Caner, and Bahram, Seiamak

Published
2022
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2. Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus-host disease in conjunction with the CMV status

Author

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
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4. 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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5. 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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6. The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation

Author

Süsal, Caner, Carapito, Raphael; Aouadi, Ismail; Verniquet, Martin; Untrau, Meiggie; Pichot, Angelique; Beaudrey, Thomas; Bassand, Xavier; Meyer, Sebastien; Faucher, Loic; Posson, Juliane; Morlon, Aurore; Kotova, Irina; Delbos, Florent; Walencik, Alexandre; Aarnink, Alice; Kennel, Anne; Suberbielle, Caroline; Taupin, Jean-Luc; Matern, Benedict M.; Spierings, Eric; Congy-Jolivet, Nicolas; Essaydi, Arnaud; Perrin, Peggy; Blancher, Antoine; Charron, Dominique; Cereb, Nezih; Maumy-Bertrand, Myriam; Bertrand, Frederic; Garrigue, Valerie; Pernin, Vincent; Weekers, Laurent; Naesens, Maarten; Kamar, Nassim; Legendre, Christophe; Glotz, Denis; Caillard, Sophie; Ladriere, Marc; Giral, Magali; Anglicheau, Dany; Bahram, Seiamak, School of Medicine, Süsal, Caner, Carapito, Raphael; Aouadi, Ismail; Verniquet, Martin; Untrau, Meiggie; Pichot, Angelique; Beaudrey, Thomas; Bassand, Xavier; Meyer, Sebastien; Faucher, Loic; Posson, Juliane; Morlon, Aurore; Kotova, Irina; Delbos, Florent; Walencik, Alexandre; Aarnink, Alice; Kennel, Anne; Suberbielle, Caroline; Taupin, Jean-Luc; Matern, Benedict M.; Spierings, Eric; Congy-Jolivet, Nicolas; Essaydi, Arnaud; Perrin, Peggy; Blancher, Antoine; Charron, Dominique; Cereb, Nezih; Maumy-Bertrand, Myriam; Bertrand, Frederic; Garrigue, Valerie; Pernin, Vincent; Weekers, Laurent; Naesens, Maarten; Kamar, Nassim; Legendre, Christophe; Glotz, Denis; Caillard, Sophie; Ladriere, Marc; Giral, Magali; Anglicheau, Dany; Bahram, Seiamak, and School of Medicine

Abstract

The identity of histocompatibility loci, besides human leukocyte antigen (HLA), remains elusive. The major histocompatibility complex (MHC) class I MICA gene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45-3.11; P < 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94-7.39; P < 0.001; HR, 9.92; 95% CI: 7.43-13.20; P < 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31-199.41; P = 0.002; HR, 82.67; 95% CI: 33.67-202.97; P < 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05-1.58; P = 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02-2.86; P = 0.041). In conclusion, assessment of MICA matching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted., ‘Laboratoire d’Excellence’ (LabEx) TRANSPLANTEX; IdEx Unistra; SFRI-STRAT’US; INSERM; European Union (EU); European Regional Development Fund; INTERREG V Program; France’s National Research Agency (Agence Nationale de Recherche; ANR); Investment for the Future Program (Programme des Investissements d’Avenir; PIA); Strasbourg’s Interdisciplinary Thematic Institute (ITI) for Precision Medicine; TRANSPLANTEX NG; ITI 2021–2028 Program of the University of Strasbourg; CNRS; Institut Universitaire de France (IUF); Fédération Hospitalo-Universitaire (FHU) OMICARE; MSD Avenir ‘Autogen’

Published
2022

7. The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation

Author

CDL HLA, CTI Spierings, Infection & Immunity, Cancer, Carapito, Raphael, Aouadi, Ismail, Verniquet, Martin, Untrau, Meiggie, Pichot, Angélique, Beaudrey, Thomas, Bassand, Xavier, Meyer, Sébastien, Faucher, Loic, Posson, Juliane, Morlon, Aurore, Kotova, Irina, Delbos, Florent, Walencik, Alexandre, Aarnink, Alice, Kennel, Anne, Suberbielle, Caroline, Taupin, Jean-Luc, Matern, Benedict M, Spierings, Eric, Congy-Jolivet, Nicolas, Essaydi, Arnaud, Perrin, Peggy, Blancher, Antoine, Charron, Dominique, Cereb, Nezih, Maumy-Bertrand, Myriam, Bertrand, Frédéric, Garrigue, Valérie, Pernin, Vincent, Weekers, Laurent, Naesens, Maarten, Kamar, Nassim, Legendre, Christophe, Glotz, Denis, Caillard, Sophie, Ladrière, Marc, Giral, Magali, Anglicheau, Dany, Süsal, Caner, Bahram, Seiamak, CDL HLA, CTI Spierings, Infection & Immunity, Cancer, Carapito, Raphael, Aouadi, Ismail, Verniquet, Martin, Untrau, Meiggie, Pichot, Angélique, Beaudrey, Thomas, Bassand, Xavier, Meyer, Sébastien, Faucher, Loic, Posson, Juliane, Morlon, Aurore, Kotova, Irina, Delbos, Florent, Walencik, Alexandre, Aarnink, Alice, Kennel, Anne, Suberbielle, Caroline, Taupin, Jean-Luc, Matern, Benedict M, Spierings, Eric, Congy-Jolivet, Nicolas, Essaydi, Arnaud, Perrin, Peggy, Blancher, Antoine, Charron, Dominique, Cereb, Nezih, Maumy-Bertrand, Myriam, Bertrand, Frédéric, Garrigue, Valérie, Pernin, Vincent, Weekers, Laurent, Naesens, Maarten, Kamar, Nassim, Legendre, Christophe, Glotz, Denis, Caillard, Sophie, Ladrière, Marc, Giral, Magali, Anglicheau, Dany, Süsal, Caner, and Bahram, Seiamak

Published
2022

8. ZMIZ1 Variants Cause a Syndromic Neurodevelopmental Disorder

Author

Carapito, Raphael, Ivanova, Ekaterina L., Morlon, Aurore, Meng, Linyan, Molitor, Anne, Erdmann, Eva, Kieffer, Bruno, Pichot, Angélique, Naegely, Lydie, Kolmer, Aline, Paul, Nicodème, Hanauer, Antoine, Tran Mau-Them, Frédéric, Jean-Marçais, Nolwenn, Hiatt, Susan M., Cooper, Gregory M., Tvrdik, Tatiana, Muir, Alison M., Dimartino, Clémantine, Chopra, Maya, Amiel, Jeanne, Gordon, Christopher T., Dutreux, Fabien, Garde, Aurore, Thauvin-Robinet, Christel, Wang, Xia, Leduc, Magalie S., Phillips, Meredith, Crawford, Heather P., Kukolich, Mary K., Hunt, David, Harrison, Victoria, Kharbanda, Mira, Smigiel, Robert, Gold, Nina, Hung, Christina Y., Viskochil, David H., Dugan, Sarah L., Bayrak-Toydemir, Pinar, Joly-Helas, Géraldine, Guerrot, Anne-Marie, Schluth-Bolard, Caroline, Rio, Marlène, Wentzensen, Ingrid M., McWalter, Kirsty, Schnur, Rhonda E., Lewis, Andrea M., Lalani, Seema R., Mensah-Bonsu, Noël, Céraline, Jocelyn, Sun, Zijie, Ploski, Rafal, Bacino, Carlos A., Mefford, Heather C., Faivre, Laurence, Bodamer, Olaf, Chelly, Jamel, Isidor, Bertrand, and Bahram, Seiamak

Published
2019
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9. 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

11. ZMIZ1 Variants Cause a Syndromic Neurodevelopmental Disorder

Author

Carapito, Raphael, primary, Ivanova, Ekaterina L., additional, Morlon, Aurore, additional, Meng, Linyan, additional, Molitor, Anne, additional, Erdmann, Eva, additional, Kieffer, Bruno, additional, Pichot, Angélique, additional, Naegely, Lydie, additional, Kolmer, Aline, additional, Paul, Nicodème, additional, Hanauer, Antoine, additional, Tran Mau-Them, Frédéric, additional, Jean-Marçais, Nolwenn, additional, Hiatt, Susan M., additional, Cooper, Gregory M., additional, Tvrdik, Tatiana, additional, Muir, Alison M., additional, Dimartino, Clémantine, additional, Chopra, Maya, additional, Amiel, Jeanne, additional, Gordon, Christopher T., additional, Dutreux, Fabien, additional, Garde, Aurore, additional, Thauvin-Robinet, Christel, additional, Wang, Xia, additional, Leduc, Magalie S., additional, Phillips, Meredith, additional, Crawford, Heather P., additional, Kukolich, Mary K., additional, Hunt, David, additional, Harrison, Victoria, additional, Kharbanda, Mira, additional, Smigiel, Robert, additional, Gold, Nina, additional, Hung, Christina Y., additional, Viskochil, David H., additional, Dugan, Sarah L., additional, Bayrak-Toydemir, Pinar, additional, Joly-Helas, Géraldine, additional, Guerrot, Anne-Marie, additional, Schluth-Bolard, Caroline, additional, Rio, Marlène, additional, Wentzensen, Ingrid M., additional, McWalter, Kirsty, additional, Schnur, Rhonda E., additional, Lewis, Andrea M., additional, Lalani, Seema R., additional, Mensah-Bonsu, Noël, additional, Céraline, Jocelyn, additional, Sun, Zijie, additional, Ploski, Rafal, additional, Bacino, Carlos A., additional, Mefford, Heather C., additional, Faivre, Laurence, additional, Bodamer, Olaf, additional, Chelly, Jamel, additional, Isidor, Bertrand, additional, and Bahram, Seiamak, additional

Published
2020
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12. The MHC class I MICAgene is a histocompatibility antigen in kidney transplantation

Author

Carapito, Raphael, Aouadi, Ismail, Verniquet, Martin, Untrau, Meiggie, Pichot, Angélique, Beaudrey, Thomas, Bassand, Xavier, Meyer, Sébastien, Faucher, Loic, Posson, Juliane, Morlon, Aurore, Kotova, Irina, Delbos, Florent, Walencik, Alexandre, Aarnink, Alice, Kennel, Anne, Suberbielle, Caroline, Taupin, Jean-Luc, Matern, Benedict M., Spierings, Eric, Congy-Jolivet, Nicolas, Essaydi, Arnaud, Perrin, Peggy, Blancher, Antoine, Charron, Dominique, Cereb, Nezih, Maumy-Bertrand, Myriam, Bertrand, Frédéric, Garrigue, Valérie, Pernin, Vincent, Weekers, Laurent, Naesens, Maarten, Kamar, Nassim, Legendre, Christophe, Glotz, Denis, Caillard, Sophie, Ladrière, Marc, Giral, Magali, Anglicheau, Dany, Süsal, Caner, and Bahram, Seiamak

Abstract

The identity of histocompatibility loci, besides human leukocyte antigen (HLA), remains elusive. The major histocompatibility complex (MHC) class I MICAgene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICAmismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45–3.11; P< 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94–7.39; P< 0.001; HR, 9.92; 95% CI: 7.43–13.20; P< 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31–199.41; P= 0.002; HR, 82.67; 95% CI: 33.67–202.97; P< 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05–1.58; P= 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02–2.86; P= 0.041). In conclusion, assessment of MICAmatching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted.

Published
2022
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14. Multi-OMICS analyses unveil STAT1 as a potential modifier gene in mevalonate kinase deficiency

Author

Carapito, Raphael, Carapito, Christine, Morlon, Aurore, Paul, Nicodème, Vaca Jacome, Alvaro Sebastian, Alsaleh, Ghada, Rolli, Véronique, Tahar, Ouria, Aouadi, Ismaïl, Rompais, Magali, Delalande, Francois, Pichot, Angélique, Georgel, Philippe, Messer, Laurent, Sibilia, Jean, Cianférani, Sarah, Van Dorsselaer, Alain, Bahram, Seiamak, Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Functional Genomics and Cancer, Service de rhumatologie (Hôpitaux Civils de Colmar), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Immunorhumathologie moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gaillard, Brigitte, and Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Proteomics, Genes, Modifier, gene polymorphism, Gene Expression Profiling, Mutation, Missense, Middle Aged, Polymorphism, Single Nucleotide, Phenotype, STAT1 Transcription Factor, inflammation, [CHIM] Chemical Sciences, Humans, [CHIM]Chemical Sciences, Exome, Female, Mevalonate Kinase Deficiency, Basic and Translational Research, familial mediterranean fever
Abstract

International audience; Objectives The objective of the present study was to explain why two siblings carrying both the same homozygous pathogenic mutation for the autoinflammatory disease hyper IgD syndrome, show opposite phenotypes, that is, the first being asymptomatic, the second presenting all classical characteristics of the disease.Methods Where single omics (mainly exome) analysis fails to identify culprit genes/mutations in human complex diseases, multiomics analyses may provide solutions, although this has been seldom used in a clinical setting. Here we combine exome, transcriptome and proteome analyses to decipher at a molecular level, the phenotypic differences between the two siblings.Results This multiomics approach led to the identification of a single gene—STAT1—which harboured a rare missense variant and showed a significant overexpression of both mRNA and protein in the symptomatic versus the asymptomatic sister. This variant was shown to be of gain of function nature, involved in an increased activation of the Janus kinase/signal transducer and activator of transcription signalling (JAK/STAT) pathway, known to play a critical role in inflammatory diseases and for which specific biotherapies presently exist. Pathway analyses based on information from differentially expressed transcripts and proteins confirmed the central role of STAT1 in the proposed regulatory network leading to an increased inflammatory phenotype in the symptomatic sibling.Conclusions This study demonstrates the power of a multiomics approach to uncover potential clinically actionable targets for a personalised therapy. In more general terms, we provide a proteogenomics analysis pipeline that takes advantage of subject-specific genomic and transcriptomic information to improve protein identification and hence advance individualised medicine.This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Published
2018
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15. 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

16. 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

17. Multi-OMICS analyses unveil as a potential modifier gene in mevalonate kinase deficiency.

Author

Carapito, Raphael, Carapito, Christine, Morlon, Aurore, Paul, Nicodème, Jacome, Alvaro Sebastian Vaca, Alsaleh, Ghada, Rolli, Véronique, Tahar, Ouria, Aouadi, Ismail, Rompais, Magali, Delalande, François, Pichot, Angélique, Georgel, Philippe, Messer, Laurent, Sibilia, Jean, Cianferani, Sarah, Van Dorsselaer, Alain, Bahram, Seiamak, and Vaca Jacome, Alvaro Sebastian

Abstract

Objectives: The objective of the present study was to explain why two siblings carrying both the same homozygous pathogenic mutation for the autoinflammatory disease hyper IgD syndrome, show opposite phenotypes, that is, the first being asymptomatic, the second presenting all classical characteristics of the disease.Methods: Where single omics (mainly exome) analysis fails to identify culprit genes/mutations in human complex diseases, multiomics analyses may provide solutions, although this has been seldom used in a clinical setting. Here we combine exome, transcriptome and proteome analyses to decipher at a molecular level, the phenotypic differences between the two siblings.Results: This multiomics approach led to the identification of a single gene-STAT1-which harboured a rare missense variant and showed a significant overexpression of both mRNA and protein in the symptomatic versus the asymptomatic sister. This variant was shown to be of gain of function nature, involved in an increased activation of the Janus kinase/signal transducer and activator of transcription signalling (JAK/STAT) pathway, known to play a critical role in inflammatory diseases and for which specific biotherapies presently exist. Pathway analyses based on information from differentially expressed transcripts and proteins confirmed the central role of STAT1 in the proposed regulatory network leading to an increased inflammatory phenotype in the symptomatic sibling.Conclusions: This study demonstrates the power of a multiomics approach to uncover potential clinically actionable targets for a personalised therapy. In more general terms, we provide a proteogenomics analysis pipeline that takes advantage of subject-specific genomic and transcriptomic information to improve protein identification and hence advance individualised medicine. [ABSTRACT FROM AUTHOR]

Published
2018
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19. 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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21. Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD.

Author

Jung, Nicolas, Kwemou, Marius, Untrau, Meiggie, Pichot, Angélique, Macquin, Cécile, Ilias, Wassila, Carapito, Raphael, Michel, Sandra, Bahram, Seiamak, Paillard, Catherine, Oudshoorn, Machteld, Claas, Frans, van der Holt, Bronno, Labalette, Myriam, Spierings, Eric, Picard, Christophe, Tamouza, Ryad, Charron, Dominique, Giacometti, Gaëlle, and Morlon, Aurore

Subjects
*GRAFT versus host disease, *HEMATOPOIETIC stem cell transplantation, *HEMATOPOIETIC stem cells, *LYMPHOCYTES, *LEUKEMIA
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, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 10/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA. MICA mismatches 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 MICA and HLA-B renders identifying a MICA-matched donor readily feasible in clinical practice. [ABSTRACT FROM AUTHOR]

Published
2016
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22. The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation

Author

Raphael Carapito, Ismail Aouadi, Martin Verniquet, Meiggie Untrau, Angélique Pichot, Thomas Beaudrey, Xavier Bassand, Sébastien Meyer, Loic Faucher, Juliane Posson, Aurore Morlon, Irina Kotova, Florent Delbos, Alexandre Walencik, Alice Aarnink, Anne Kennel, Caroline Suberbielle, Jean-Luc Taupin, Benedict M. Matern, Eric Spierings, Nicolas Congy-Jolivet, Arnaud Essaydi, Peggy Perrin, Antoine Blancher, Dominique Charron, Nezih Cereb, Myriam Maumy-Bertrand, Frédéric Bertrand, Valérie Garrigue, Vincent Pernin, Laurent Weekers, Maarten Naesens, Nassim Kamar, Christophe Legendre, Denis Glotz, Sophie Caillard, Marc Ladrière, Magali Giral, Dany Anglicheau, Caner Süsal, Seiamak Bahram, Süsal, Caner, Carapito, Raphael, Aouadi, Ismail, Verniquet, Martin, Untrau, Meiggie, Pichot, Angelique, Beaudrey, Thomas, Bassand, Xavier, Meyer, Sebastien, Faucher, Loic, Posson, Juliane, Morlon, Aurore, Kotova, Irina, Delbos, Florent, Walencik, Alexandre, Aarnink, Alice, Kennel, Anne, Suberbielle, Caroline, Taupin, Jean-Luc, Matern, Benedict M., Spierings, Eric, Congy-Jolivet, Nicolas, Essaydi, Arnaud, Perrin, Peggy, Blancher, Antoine, Charron, Dominique, Cereb, Nezih, Maumy-Bertrand, Myriam, Bertrand, Frederic, Garrigue, Valerie, Pernin, Vincent, Weekers, Laurent, Naesens, Maarten, Kamar, Nassim, Legendre, Christophe, Glotz, Denis, Caillard, Sophie, Ladriere, Marc, Giral, Magali, Anglicheau, Dany, Bahram, Seiamak, and School of Medicine

Subjects
Graft Rejection, Biochemistry & Molecular Biology, Science & Technology, HLA ANTIBODIES, Biochemistry and molecular biology, Cell biology, Medicine, Graft Survival, Histocompatibility Antigens Class I, Cell Biology, General Medicine, Research & Experimental Medicine, Kidney Transplantation, General Biochemistry, Genetics and Molecular Biology, Antibodies, Kidney transplantation, Alloantibody, Medicine, Research & Experimental, REJECTION, Humans, Life Sciences & Biomedicine
Abstract

The identity of histocompatibility loci, besides human leukocyte antigen (HLA), remains elusive. The major histocompatibility complex (MHC) class I MICA gene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45-3.11; P < 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94-7.39; P < 0.001; HR, 9.92; 95% CI: 7.43-13.20; P < 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31-199.41; P = 0.002; HR, 82.67; 95% CI: 33.67-202.97; P < 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05-1.58; P = 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02-2.86; P = 0.041). In conclusion, assessment of MICA matching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted., ‘Laboratoire d’Excellence’ (LabEx) TRANSPLANTEX; IdEx Unistra; SFRI-STRAT’US; INSERM; European Union (EU); European Regional Development Fund; INTERREG V Program; France’s National Research Agency (Agence Nationale de Recherche; ANR); Investment for the Future Program (Programme des Investissements d’Avenir; PIA); Strasbourg’s Interdisciplinary Thematic Institute (ITI) for Precision Medicine; TRANSPLANTEX NG; ITI 2021–2028 Program of the University of Strasbourg; CNRS; Institut Universitaire de France (IUF); Fédération Hospitalo-Universitaire (FHU) OMICARE; MSD Avenir ‘Autogen’

Published
2021

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

Author

Christophe Picard, Cécile Macquin, Sergi Querol, Catherine Paillard, Katharina Fleischhauer, Gaëlle Giacometti, Bronno van der Holt, Ibrahim Yakoub-Agha, Wassila Ilias, Anne Cesbron, Myriam Labopin, Masao Ota, Jorge Sierra, Fabio Ciceri, Dominique Charron, Ryad Tamouza, Régis Peffault de Latour, Xavier Lafarge, Katia Gagne, Seiamak Bahram, Myriam Maumy-Bertrand, Meiggie Untrau, Pascale Loiseau, Raphael Carapito, Jürgen Kuball, Bruno Lioure, Frans H.J. Claas, Noel Milpied, Antoine Toubert, Jan J. Cornelissen, Irina Kotova, Philippe Moreau, Eric Spierings, Mauricette Michallet, Arnon Nagler, Annette Schmitt-Graeff, Angélique Pichot, Petya Apostolova, Mohamad Mohty, Aurore Morlon, Myriam Labalette, Nicolas Jung, Didier Blaise, Yoshihiko Katsuyama, Hidetoshi Inoko, A. Parissiadis, Frédéric Bertrand, Marius Kwemou, Sandra Michel, Machteld Oudshoorn, Gérard Socié, Robert Zeiser, Peter A. von dem Borne, Valérie Dubois, Luca Vago, Carapito, Raphael, Jung, Nicola, Kwemou, Mariu, 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, De Latour, Régis Peffault, Blaise, Didier, Cornelissen, Jan J., Yakoub Agha, Ibrahim, Claas, Fran, Moreau, Philippe, Milpied, Noël, Charron, Dominique, Mohty, Mohamad, Zeiser, Robert, Socié, Gérard, Bahram, Seiamak, inconnu, Inconnu, Institut de Recherche Mathématique Avancée (IRMA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Mathématiques et Modélisation d'Evry (LaMME), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), laboratoire d'Etudes et de recherches en Statistiques et Développement (LERSTAD), Université Gaston Bergé Sénégal, Laboratoire d'Acoustique Environnementale (IFSTTAR/AME/LAE), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université de Lyon-PRES Université Nantes Angers Le Mans (UNAM), Physique des interactions ioniques et moléculaires (PIIM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Etablissement Français du Sang [Nantes], Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Service de pneumologie [Rennes] = Pneumology [Rennes], CHU Pontchaillou [Rennes], Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Alloimmunité-Autoimmunité-Transplantation (A2T), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Sociétés, Acteurs, Gouvernement en Europe (SAGE), Politique, Religion, Institutions et Sociétés : Mutations Européennes - Groupe de Sociologie Politique Européenne (PRISME-GSPE), Centre National de la Recherche Scientifique (CNRS), Centre de Transfusion Sanguine Aquitaine-Limousin (CTS AQUITAINE-LIMOUSIN), Centre de Transfusion Sanguine, Ospedale San Raffaele, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Barcelona Cord Blood Bank, Agrosystèmes tropicaux (ASTRO), Institut National de la Recherche Agronomique (INRA), Chaim Sheba Medical Center [Ramat Gan, Israel], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Université Paris Diderot - Paris 7 (UPD7), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigations Biomédicales-Hématologie, Oncologie et Greffes (CIB-HOG), Hôpital St Louis, Assistance Publique des Hôpitaux de Paris (AP-HP), Centre d'Investigations Biomédicales-Hématologie, Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-ENSIIE-Centre National de la Recherche Scientifique (CNRS), Service de pneumologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), ALWP-EBMT & Département d'hématologie et de thérapie cellulaire [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Hematology, Institut de Recherche Mathématique Avancée ( IRMA ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Mathématiques et Modélisation d'Evry ( LaMME ), Institut National de la Recherche Agronomique ( INRA ) -Université d'Évry-Val-d'Essonne ( UEVE ) -ENSIIE-Centre National de la Recherche Scientifique ( CNRS ), laboratoire d'Etudes et de recherches en Statistiques et Développement ( LERSTAD ), Laboratoire d'Acoustique Environnementale ( IFSTTAR/AME/LAE ), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux ( IFSTTAR ) -Université de Lyon-PRES Université Nantes Angers Le Mans ( UNAM ), Laboratoire d'Histoire des Sciences et de Philosophie - Archives Henri Poincaré ( LHSP ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Physique des interactions ioniques et moléculaires ( PIIM ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Functional Genomics and Cancer, Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes], Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Alloimmunité-Autoimmunité-Transplantation ( A2T ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Politique, Religion, Institutions et Sociétés : Mutations Européennes - Groupe de Sociologie Politique Européenne ( PRISME-GSPE ), Centre National de la Recherche Scientifique ( CNRS ), Centre de Transfusion Sanguine Aquitaine-Limousin ( CTS AQUITAINE-LIMOUSIN ), Géographie de l'environnement ( GEODE ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse - Jean Jaurès ( UT2J ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Agrosystèmes tropicaux ( ASTRO ), Institut National de la Recherche Agronomique ( INRA ), Hospices Civils de Lyon ( HCL ), IFR Saint-Louis, institut d'hématologie ( ISLIH ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Erasmus MC University medical Centre / Daniel den Hoed Cancer centre, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Laboratoire de Mathématiques et Modélisation d'Evry, PRES Université Nantes Angers Le Mans (UNAM)-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Centre National de la Recherche Scientifique (CNRS)-ENSIIE-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medizin, Graft vs Host Disease, Hematopoietic stem cell transplantation, Biochemistry, Linkage Disequilibrium, immune system diseases, HLA Antigens, Cytotoxic T cell, Child, ComputingMilieux_MISCELLANEOUS, HLA-DQB1, biology, Histocompatibility Testing, Incidence, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Allografts, 3. Good health, surgical procedures, operative, NK Cell Lectin-Like Receptor Subfamily K, Child, Preschool, Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Adult, Adolescent, Immunology, Human leukocyte antigen, 03 medical and health sciences, MHC class I, medicine, Journal Article, Humans, Aged, Retrospective Studies, Transplantation, [ SDV ] Life Sciences [q-bio], Histocompatibility Antigens Class I, Infant, Newborn, Infant, Cell Biology, medicine.disease, Histocompatibility, stomatognathic diseases, 030104 developmental biology, Graft-versus-host disease, Chronic Disease, biology.protein
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, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 10/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA. MICA mismatches 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 MICA and HLA-B renders identifying a MICA-matched donor readily feasible in clinical practice.

Published
2016
Full Text
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24. Multi-OMICS analyses unveil STAT1 as a potential modifier gene in mevalonate kinase deficiency.

Author

Carapito R, Carapito C, Morlon A, Paul N, Vaca Jacome AS, Alsaleh G, Rolli V, Tahar O, Aouadi I, Rompais M, Delalande F, Pichot A, Georgel P, Messer L, Sibilia J, Cianferani S, Van Dorsselaer A, and Bahram S

Subjects
Adult, Exome, Female, Gene Expression Profiling methods, Humans, Middle Aged, Mutation, Missense, Phenotype, Polymorphism, Single Nucleotide, Proteomics methods, Genes, Modifier, Mevalonate Kinase Deficiency genetics, STAT1 Transcription Factor genetics
Abstract

Objectives: The objective of the present study was to explain why two siblings carrying both the same homozygous pathogenic mutation for the autoinflammatory disease hyper IgD syndrome, show opposite phenotypes, that is, the first being asymptomatic, the second presenting all classical characteristics of the disease., Methods: Where single omics (mainly exome) analysis fails to identify culprit genes/mutations in human complex diseases, multiomics analyses may provide solutions, although this has been seldom used in a clinical setting. Here we combine exome, transcriptome and proteome analyses to decipher at a molecular level, the phenotypic differences between the two siblings., Results: This multiomics approach led to the identification of a single gene -STAT1 -which harboured a rare missense variant and showed a significant overexpression of both mRNA and protein in the symptomatic versus the asymptomatic sister. This variant was shown to be of gain of function nature, involved in an increased activation of the Janus kinase/signal transducer and activator of transcription signalling (JAK/STAT) pathway, known to play a critical role in inflammatory diseases and for which specific biotherapies presently exist. Pathway analyses based on information from differentially expressed transcripts and proteins confirmed the central role of STAT1 in the proposed regulatory network leading to an increased inflammatory phenotype in the symptomatic sibling., Conclusions: This study demonstrates the power of a multiomics approach to uncover potential clinically actionable targets for a personalised therapy. In more general terms, we provide a proteogenomics analysis pipeline that takes advantage of subject-specific genomic and transcriptomic information to improve protein identification and hence advance individualised medicine., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2018
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26. TAB2, TRAF6 and TAK1 are involved in NF-kappaB activation induced by the TNF-receptor, Edar and its adaptator Edaradd.

Author

Morlon A, Munnich A, and Smahi A

Subjects
Adaptor Proteins, Signal Transducing genetics, Amino Acid Sequence, Cells, Cultured, Edar Receptor, Edar-Associated Death Domain Protein, Humans, I-kappa B Kinase metabolism, Immunoprecipitation, MAP Kinase Kinase Kinases genetics, Molecular Sequence Data, Mutation, Receptors, Ectodysplasin, Receptors, Tumor Necrosis Factor metabolism, Signal Transduction, TNF Receptor-Associated Factor 6 genetics, Two-Hybrid System Techniques, Adaptor Proteins, Signal Transducing metabolism, Ectodermal Dysplasia metabolism, MAP Kinase Kinase Kinases metabolism, NF-kappa B metabolism, TNF Receptor-Associated Factor 6 metabolism, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins metabolism
Abstract

Activation of the NF-kappaB pathway by the TNF-receptor Edar (Ectodysplasin receptor) and its downstream adaptator Edaradd (Edar-associated death domain) is essential for the development of hair follicles, teeth, exocrine glands and other ectodermal derivatives. Dysfunction of Edar signalling causes hypohidrotic/anhidrotic ectodermal dysplasia (ED), a disorder characterized by sparse hair, lack of sweat glands and malformation of teeth. The Edar signalling pathway stimulates NF-kappaB transcription factors via an activation of the IkappaB kinase (IKK) complex. To gain further insight into the mechanism of IKK activation by Edar and Edaradd, we performed a yeast two-hybrid screen and isolated TAB2 (TAK1-binding protein 2) as a binding partner of Edaradd. TAB2 is an adaptator protein that brigdes TRAF6 (TNF-receptor-associated factor 6) to TAK1 (TGFbeta-activated kinase 1), allowing TAK1 activation and subsequent IKK activation. Here, we show that endogenous and overexpressed TAB2, TRAF6 and TAK1 co-immunoprecipitated with Edaradd in 293 cells. Moreover, we show that dominant negative forms of TAB2, TRAF6 and TAK1 blocked the NF-kappaB activation induced by Edaradd. These results support the involvement of the TAB2/TRAF6/TAK1 signalling complex in the Edar signal transduction pathway and have important implications for our understanding of NF-kappaB activation and EDs in human.

Published
2005
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