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13. La supplémentation maternelle en prébiotiques pendant la grossesse régule la colonisation du microbiote des enfants à haut-risque de dermatite atopique, mais ne prévient pas la maladie à l’âge d’un an. Un essai contrôlé randomisé multicentrique

Author

Barbarot, S., Aubert, H., Boivin, M., Brosseau, C., Foureau, A., Cherbuy, C., Dhily, E., Larsen, M., Maruani, A., Droitcourt, C., Mazereeuw-Hautier, J., Faurel-Paul, E., Le Thuaut, A., Tching-Sin, M., Dochez, V., and Bodinier, M.

Abstract

De nouvelles stratégies de prévention primaire de la dermatite atopique (DA) sont nécessaires dans le but de réduire la fréquence et la sévérité de cette maladie. Les maladies atopiques sont associées à une perturbation de l’équilibre microbien intestinal au début de la vie. Les prébiotiques sont des sucres aux propriétés immunomodulatrices qui stimulent la diversité du microbiote digestif. Jusqu’à présent, la plupart des essais cliniques de prévention primaire se sont concentrés sur l’amélioration de la colonisation intestinale postnatale des nourrissons. Cependant, la vie prénatale est une période cruciale au cours de laquelle différents mécanismes de tolérance sont mis en place et des études précliniques chez la souris ont montré que l’apport maternel en prébiotique réduisait le risque d’allergie alimentaire chez la progéniture. Nous avons cherché à déterminer si la supplémentation anténatale en prébiotiques pendant la grossesse était susceptible de prévenir la DA chez les enfants à risque.

Published
2024
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14. Transplacental innate immune training via maternal microbial exposure: Role of XBP1-ERN1 axis in dendritic cell precursor programming

Author

Mincham, K.T., Jones, A.C., Bodinier, M., Scott, N.M., Lauzon-Joset, J-F, Stumbles, P.A., Bosco, A., Holt, P.G., Strickland, D.H., Mincham, K.T., Jones, A.C., Bodinier, M., Scott, N.M., Lauzon-Joset, J-F, Stumbles, P.A., Bosco, A., Holt, P.G., and Strickland, D.H.

Abstract

We recently reported that offspring of mice treated during pregnancy with the microbial-derived immunomodulator OM-85 manifest striking resistance to allergic airways inflammation, and localized the potential treatment target to fetal conventional dendritic cell (cDC) progenitors. Here, we profile maternal OM-85 treatment-associated transcriptomic signatures in fetal bone marrow, and identify a series of immunometabolic pathways which provide essential metabolites for accelerated myelopoiesis. Additionally, the cDC progenitor compartment displayed treatment-associated activation of the XBP1-ERN1 signalling axis which has been shown to be crucial for tissue survival of cDC, particularly within the lungs. Our forerunner studies indicate uniquely rapid turnover of airway mucosal cDCs at baseline, with further large-scale upregulation of population dynamics during aeroallergen and/or pathogen challenge. We suggest that enhanced capacity for XBP1-ERN1-dependent cDC survival within the airway mucosal tissue microenvironment may be a crucial element of OM-85-mediated transplacental innate immune training which results in postnatal resistance to airway inflammatory disease.

Published
2020

20. Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

Author

Pouessel, G, Claverie, C, Labreuche, J, Renaudin, J-M, Dorkenoo, A, Eb, M, Moneret-Vautrin, A, Deschildre, A, Leteurtre, S, Grabenhenrich, L, Worm, M, Dölle, S, Scherer, K, Hutteger, I, Christensen, M, Bindslev-Jensen, C, Mortz, C, Eller, E, Kjaer, HF, Carneiro-Leão, L, Badas, J, Coimbra, A, Levy, DP, Ben-Shoshan, M, Rimon, A, Benor, S, Arends, NJT, Edelbroek, N, de Groot, H, Emons, JAM, Brand, HKA, Verhoeven, D, van Veen, LN, de Jong, NW, Noh, G, Jang, EH, Pascal, M, Dominguez, O, Piquer, M, Alvaro, M, Jimenez-Feijoo, R, Lozano, J, Machinena, A, del Mar Folqué, M, Giner, MT, Plaza, AM, Turner, P, Patel, N, Vazquez-Ortiz, M, Lindsley, S, Walker, L, Rosenberg, S, Mari, A, Alessandri, C, Giangrieco, I, Tuppo, L, Rafaiani, C, Mitterer, G, Ciancamerla, M, Ferrara, R, Bernardi, ML, Zennaro, D, Tamburrini, M, Ciardiello, MA, Harwanegg, C, Fernandez, A, Selb, R, Egenmann, P, Epstein, M, Hoffmann-Sommergruber, K, Koning, F, Lovik, M, Clare Mills, EN, Moreno, J, van Loveren, H, Wal, J-M, Diesner, S, Bergmayr, C, Pfitzner, B, Assmann, VE, Starkl, P, Endesfelder, D, Eiwegger, T, Szepfalusi, Z, Fehrenbach, H, Jensen-Jarolim, E, Hartmann, A, Pali-Schöll, I, Untersmayr, E, Wille, S, Meyer, P, Klingebiel, C, Lidholm, J, Ehrenberg, A, Östling, J, Cleach, I, Mège, J-L, Vitte, J, Aina, R, Dubiela, P, Pfeifer, S, Bublin, M, Radauer, C, Humeniuk, P, Kabasser, S, Asero, R, Bogas, G, Gomez, F, Campo, P, Salas, M, Doña, I, Barrionuevo, E, Guerrero, MA, Mayorga, C, Prieto, A, Barber, D, Torres, MJ, Jamin, A, Wangorsch, A, Ballmer, B, Vieths, S, Scheurer, S, Apostolovic, D, Mihailovic, J, Krstic, M, Starkhammar, M, Velickovic, TC, Hamsten, C, van Hage, M, van Erp, FC, Knol, EF, Kansen, HM, Pontoppidan, B, Meijer, Y, van der Ent, CK, Knulst, AC, Sayers, R, Brown, H, Custovic, A, Simpson, A, Mills, C, Schulz, J, Akkerdaas, J, Totis, M, Capt, A, Herouet-Guicheney, C, van Ree, R, Banerjee, T, Banerjee, A, Claude, M, Bouchaud, G, Lupi, R, Castan, L, Tranquet, O, Denery-Papini, S, Bodinier, M, Brossard, C, De Poi, R, Gritti, E, De Dominicis, E, Popping, B, de Laureto, PP, Palosuo, K, Kukkonen, AK, Pelkonen, A, Mäkelä, M, Lee, NA, Rost, J, Muralidharan, S, Campbell, D, Mehr, S, Nock, C, Baumert, J, Taylor, S, Mastrorilli, C, Tripodi, S, Caffarelli, C, Perna, S, Di Rienzo Businco, A, Sfika, I, Dondi, A, Bianchi, A, Dascola, CP, Ricci, G, Cipriani, F, Maiello, N, del Giudice, MM, Frediani, T, Frediani, S, Macrì, F, Pistoletti, C, Iacono, ID, Patria, MF, Varin, E, Peroni, D, Comberiati, P, Chini, L, Moschese, V, Lucarelli, S, Bernardini, R, Pingitore, G, Pelosi, U, Olcese, R, Moretti, M, Cirisano, A, Faggian, D, Travaglini, A, Plebani, M, Verga, MC, Calvani, M, Giordani, P, Matricardi, PM, Ontiveros, N, Cabrera-Chavez, F, Galand, J, Beaudouin, E, Pineau, F, Sakai, S, Matsunaga, K, Teshima, R, Larré, C, Denery, S, Tschirner, S, Trendelenburg, V, Schulz, G, Niggemann, B, Beyer, K, Bouferkas, Y, Belabbas, Y, Saidi, D, Kheroua, O, Mecherfi, KEE, Guendouz, M, Haddi, A, Kaddouri, H, Amaral, L, Pereira, A, Rodrigues, S, Datema, M, Jongejan, L, Clausen, M, Knulst, A, Papadopoulos, N, Kowalski, M, de Blay, F, Zwinderman, A, Hoffman-Sommergruber, K, Ballmer-Weber, B, Fernandez-Rivas, M, Deng, S, Yin, J, Eisenmann, C, Nassiri, M, Reinert, R, van der Valk, JPM, van Wijk, RG, Vergouwe, Y, Steyerberg, EW, Reitsma, M, Wichers, HJ, Savelkoul, HFJ, Vlieg-Boerstra, B, Dubois, AEJ, Carolino, F, Rodolfo, A, Cernadas, J, Roa-Medellín, D, Rodriguez-Fernandez, A, Navarro, J, Albendiz, V, Baeza, ML, Intente-Herrero, S, Mikkelsen, A, Mehlig, K, Lissner, L, Verrill, L, Luccioli, S, van Bilsen, J, Kuper, F, Wolterbeek, A, Rankouhi, TR, Verschuren, L, Cnossen, H, Jeurink, P, Garssen, J, Knippels, L, Garthoff, J, Houben, G, Leeman, W, Eleonore Pettersson, M, Schins, AMM, Koppelman, GH, Kollen, BJ, Zubchenko, S, Kuntz, S, Mérida, P, Álvaro, M, Riggioni, C, Castellanos, JH, Jimenez, R, Cap, M, Drumez, E, Lejeune, S, Thumerelle, C, Mordacq, C, Nève, V, Ricò, S, Varini, M, Nocerino, R, Cosenza, L, Amoroso, A, Di Costanzo, M, Di Scala, C, Bedogni, G, Canani, RB, Turner, PJ, Poza-Guedes, P, González-Pérez, R, Sánchez-Machín, I, Matheu-Delgado, V, Wambre, E, Ballegaard, A-S, Madsen, C, Gregersen, J, Bøgh, KL, Aubert, P, Neunlist, M, Magnan, A, Lozano-Ojalvo, D, Pablos-Tanarro, A, Pérez-Rodríguez, L, Molina, E, López-Fandiño, R, Rekima, A, Macchiaverni, P, Turfkruyer, M, Holvoet, S, Dupuis, L, Baiz, N, Annesi-Maesano, I, Mercenier, A, Nutten, S, Verhasselt, V, Mrakovcic-Sutic, I, Banac, S, Sutic, I, Baricev-Novakovic, Z, Pavisic, V, Muñoz-Cano, R, Jiménez-Rodríguez, T, Corbacho, D, Roca-Ferrer, J, Bartra, J, Bulog, A, Micovic, V, Markiewicz, L, Szymkiewicz, A, Szyc, A, Wróblewska, B, Harvey, BM, Harthoorn, LF, Wesley Burks, A, Rentzos, G, Björk, A-LB, Bengtsson, U, Barber, C, Kalicinsky, C, Breynaert, C, Coorevits, L, Jansen, C, Van Hoeyveld, E, Verbeke, K, Kochuyt, A-M, Schrijvers, R, Deleanu, D, Muntean, A, Konstantakopoulou, M, Pasioti, M, Papadopoulou, A, Iliopoulou, A, Mikos, N, Kompoti, E, de Castro, ED, Bartalomé, B, Ue, KL, Griffiths, E, Till, S, Grimshaw, K, Roberts, G, Selby, A, Butiene, I, Larco, JI, Dubakiene, R, Fiandor, A, Fiocchi, A, Sigurdardottir, S, Sprikkelman, A, Schoemaker, A-F, Xepapadaki, P, Keil, T, Cojocariu, Z, Barbado, BS, Iancu, V, Arroabarren, E, Esarte, MG, Arteaga, M, Andrade, MC, Borges, D, Kalil, J, Bianchi, PG, Agondi, RC, Gupta, RK, Sharma, A, Gupta, K, Das, M, Dwivedi, P, Karseladze, R, Jorjoliani, L, Saginadze, L, Tskhakaia, M, Basello, K, Piuri, G, Speciani, AF, Speciani, MC, Camerotto, C, Zinno, F, Pakholchuk, O, Nedelska, S, Pattini, S, Costantino, MT, Peveri, S, Villalta, D, Savi, E, Costanzi, A, Revyakina, VA, Kiseleva, MA, Kuvshinova, ED, Larkova, IA, Shekhetov, AA, Silva, D, Moreira, A, Plácido, J, van der Kleij, H, van Twuijver, E, Sutorius, R, de Kam, P-J, van Odijk, J, Lindqvist, H, Lustig, E, Jácome, AAA, Aguilar, KLB, Domínguez, MG, Hernández, DAM, Caruso, C, Casale, C, Rapaccini, GL, Romano, A, De Vitis, I, Cocco, RR, Aranda, C, Mallozi, MC, Motta, JF, Moraes, L, Pastorino, A, Rosario, N, Goudouris, E, Porto, A, Wandalsen, NF, Sarinho, E, Sano, F, Solé, D, Pitsios, C, Petrodimopoulou, M, Papadopoulou, E, Passioti, M, Kontogianni, M, Adamia, N, Khaleva, E, del Prado, AP, Du Toit, G, Krzych, E, Samolinska-Zawisza, U, Furmanczyk, K, Tomaszewska, A, Raciborski, F, Lipiec, A, Samel-Kowalik, P, Walkiewicz, A, Borowicz, J, Samolinski, B, Nano, AL, Recto, M, Somoza, ML, López, NB, Alzate, DP, Ruano, FJ, Garcimartín, MI, Haroun, E, de la Torre, MV, Rojas, A, Onieva, ML, Canto, G, Rodrigues, A, Forno, A, Cabral, AJ, Gonçalves, R, Vorozhko, I, Sentsova, T, Chernyak, O, Denisova, S, Ilènko, L, Muhortnich, V, Zimmermann, C, Rohrbach, A, Bakhsh, FR, Boudewijn, K, Oomkes-Pilon, A-M, Van Ginkle, D, Šilar, M, Jeverica, A, Vesel, T, Avčin, T, Korošec, P, van der Valk, J, Berends, I, Arends, N, van Maaren, M, Wichers, H, Emons, J, Dubois, A, de Jong, N, Matsyura, O, Besh, L, Huang, C-H, Jan, T-R, Stiefel, G, Tratt, J, Kirk, K, Arasi, S, Caminiti, L, Crisafulli, G, Fiamingo, C, Fresta, J, Pajno, G, Remington, B, Kruizinga, A, Marty Blom, W, Westerhout, J, Bijlsma, S, Blankestijn, M, Otten, H, Klemans, R, Michelsen-Huisman, AD, van Os-Medendorp, H, Kruizinga, AG, Versluis, A, van Duijn, G, de Zeeuw-Brouwer, HM-L, Castenmiller, JJM, Noteborn, HPJM, Houben, GF, Bravin, K, Luyt, D, Javed, B, Couch, P, Munro, C, Padfield, P, Sperrin, M, Byrne, A, Oosthuizen, L, Kelleher, C, Ward, F, Brosnan, N, King, G, Corbet, E, Guzmán, JAH, García, MB, Asensio, O, Navarrete, LV, Larramona, H, Miró, XD, Pyrz, K, Austin, M, Boloh, Y, Galloway, D, Hernandez, P, Hourihane, JOB, Kenna, F, Majkowska-Wojciechowska, B, Regent, L, Themisb, M, Schnadt, S, Semic-Jusufagic, A, Galvin, AD, Kauppila, T, Kuitunen, M, Kitsioulis, NA, Douladiris, N, Kostoudi, S, Manolaraki, I, Mitsias, D, Manousakis, E, Papadopoulos, NG, Knibb, R, Hammond, J, Cooke, R, Yrjänä, J, Hanni, A-M, Vähäsarja, P, Mustonen, O, Dunder, T, Kulmala, P, Lasa, E, D’Amelio, C, Martínez, S, Joral, A, Gastaminza, G, Goikoetxea, MJ, Candy, DCA, Van Ampting, MTJ, Oude Nijhuis, MM, Butt, AM, Peroni, DG, Fox, AT, Knol, J, Michaelis, LJ, Padua, I, Padrao, P, Moreira, P, Barros, R, Sharif, H, Ahmed, M, Gomaa, N, Mens, J, Smit, K, Timmermans, F, Poredoš, T, Jeverica, AK, Sedmak, M, Benedik, E, Accetto, M, Zupančič, M, Yonamine, G, Soldateli, G, Aquilante, B, Pastorino, AC, de Moraes Beck, CL, Gushken, AK, de Barros Dorna, M, dos Santos, CN, Castro, APM, Al-Qahtani, A, Arnaout, R, Khaliq, AR, Amin, R, Sheikh, F, Alvarez, J, Anda, M, Palacios, M, De Prada, M, Ponce, C, Balbino, B, Sibilano, R, Marichal, T, Gaudenzio, N, Karasuyama, H, Bruhns, P, Tsai, M, Reber, LL, Galli, SJ, Ferreira, AR, Cernadas, JR, del Campo García, A, Fernández, SP, Carrera, NS, Sánchez-Cruz, FB, Lorenzo, JRF, Claus, S, Pföhler, C, Ruëff, F, Treudler, R, Jaume, ME, Madroñero, A, Perez, MTG, Julia, JC, Plovdiv, CH, Gethings, L, Langridge, J, Adel-Patient, K, Bernard, H, Barcievic-Jones, I, Sokolova, R, Yankova, R, Ivanovska, M, Murdjeva, M, Popova, T, Dermendzhiev, S, Karjalainen, M, Lehnigk, U, Brown, D, Locklear, JC, Locklear, J, Maris, I, Hourihane, J, Ornelas, C, Caiado, J, Ferreira, MB, Pereira-Barbosa, M, Puente, Y, Daza, JC, Monteseirin, FJ, Ukleja-Sokolowska, N, Gawronska-Ukleja, E, Zbikowska-Gotz, M, Bartuzi, Z, Sokolowski, L, Adams, A, Mahon, B, English, K, Gourdon-Dubois, N, Sellam, L, Pereira, B, Michaud, E, Messaoudi, K, Evrard, B, Fauquert, J-L, Palomares, F, Gomez, G, Rodriguez, MJ, Galindo, L, Molina, A, Paparo, L, Mennini, M, Aitoro, R, Wawrzeńczyk, A, Przybyszewski, M, Sarıcoban, HE, Ugras, M, Yalvac, Z, Flokstra-de Blok, BMJ, van der Velde, JL, Vereda, A, Ippolito, C, Traversa, A, Adriano, D, Bianchi, DM, Gallina, S, Decastelli, L, Makatsori, M, Miles, A, Devetak, SP, Devetak, I, Tabet, SA, Trandbohus, JF, Winther, P, Malling, H-J, Hansen, KS, Garvey, LH, Wang, C-C, Cheng, Y-H, Tung, C-W, Dietrich, M, Marenholz, I, Kalb, B, Grosche, S, Blümchen, K, Schlags, R, Price, M, Rietz, S, Esparza-Gordillo, J, Lau, S, Lee, Y-A, Almontasheri, A, Bahkali, MA, Elshorbagi, S, Alfhaid, A, Altamimi, M, Madbouly, E, Al-Dhekri, H, Arnaout, RK, Basagaña, M, Miquel, S, Bartolomé, B, Brix, B, Rohwer, S, Brandhoff, S, Berger, A, Suer, W, Weimann, A, Bueno, C, Martín-Pedraza, L, Abián, S, Segundo-Acosta, PS, López-Rodríguez, JC, Barderas, R, Batanero, E, Cuesta-Herranz, J, Villalba, MT, Correia, M, Benito-Garcia, F, Arêde, C, Piedade, S, Morais-Almeida, M, Hindley, J, Yarham, R, Kuklinska-Pijanka, A, Gillick, D, Patient, K, Chapman, MD, Miranda, A, Matos, E, Sokolova, A, Rao, H, Baricevic-Jones, I, Smith, F, Xue, W, Magnusdottir, H, Vidarsdottir, AG, Lund, S, Jensen, AB, Ludviksson, BR, Simon, R, Elfont, R, Bennett, S, Voyksner, R, de Lurdes Torre, M, Yürek, S, Faber, MA, Bastiaensen, A, Mangodt, E, van Gasse, A, Decuyper, I, Sabato, V, Hagendorens, MM, Bridts, CH, De Clerck, LS, Ebo, D, Schwarz, S, Ziegert, M, Albroscheit, S, Schwager, C, Kull, S, Behrends, J, Röckendorf, N, Schocker, F, Frey, A, Homann, A, Becker, W-M, Jappe, U, Zaabat, N, Osscini, S, Agabriel, C, Sterling, B, Carsin, A, Liabeuf, V, Maćków, M, Zbróg, A, Bronkowska, M, Courtois, J, Gadisseur, R, Bertholet, C, Lukas, P, Cavalier, E, Delahaut, P, Quinting, B, Gertmo, MB, Hasseus, ET, Barzylovych, V, Oliveira, J, Ensina, LF, Aranda, CS, Dopazo, L, Lopez, R, Perez, R, Santos-Diez, L, Bilbao, A, Garcia, JM, Núñez, IG, Mármol, MÁA, Villarejo, MJB, Martos, JAB, Vergara, MS, García, JMI, Michalska, A, Sergiejko, G, Zacniewski, R, Ghiordanescu, I-M, Deaconu, C, Popescu, M, Bumbacea, RS, Ibranji, A, Nikolla, E, Loloci, G, Juel-Berg, N, Larsen, LF, Poulsen, LK, Marcelino, J, Prata, R, Costa, AC, Duarte, F, Neto, M, Santos, J, Pestana, LC, Sampaio, D, Minale, P, Dignetti, P, Bignardi, D, Nedelea, I, Popescu, F-D, Vieru, M, Secureanu, F-A, Ganea, CS, Vieira, M, Silva, JPM, Watts, T, Watts, S, Lomikovska, M, Peredelskaya, M, Nenasheva, N, Filipovic, I, Zivkovic, Z, Filipovic, D, Higgs, J, Warner, A, Jones, C, Pouessel, G, Claverie, C, Labreuche, J, Renaudin, J-M, Dorkenoo, A, Eb, M, Moneret-Vautrin, A, Deschildre, A, Leteurtre, S, Grabenhenrich, L, Worm, M, Dölle, S, Scherer, K, Hutteger, I, Christensen, M, Bindslev-Jensen, C, Mortz, C, Eller, E, Kjaer, HF, Carneiro-Leão, L, Badas, J, Coimbra, A, Levy, DP, Ben-Shoshan, M, Rimon, A, Benor, S, Arends, NJT, Edelbroek, N, de Groot, H, Emons, JAM, Brand, HKA, Verhoeven, D, van Veen, LN, de Jong, NW, Noh, G, Jang, EH, Pascal, M, Dominguez, O, Piquer, M, Alvaro, M, Jimenez-Feijoo, R, Lozano, J, Machinena, A, del Mar Folqué, M, Giner, MT, Plaza, AM, Turner, P, Patel, N, Vazquez-Ortiz, M, Lindsley, S, Walker, L, Rosenberg, S, Mari, A, Alessandri, C, Giangrieco, I, Tuppo, L, Rafaiani, C, Mitterer, G, Ciancamerla, M, Ferrara, R, Bernardi, ML, Zennaro, D, Tamburrini, M, Ciardiello, MA, Harwanegg, C, Fernandez, A, Selb, R, Egenmann, P, Epstein, M, Hoffmann-Sommergruber, K, Koning, F, Lovik, M, Clare Mills, EN, Moreno, J, van Loveren, H, Wal, J-M, Diesner, S, Bergmayr, C, Pfitzner, B, Assmann, VE, Starkl, P, Endesfelder, D, Eiwegger, T, Szepfalusi, Z, Fehrenbach, H, Jensen-Jarolim, E, Hartmann, A, Pali-Schöll, I, Untersmayr, E, Wille, S, Meyer, P, Klingebiel, C, Lidholm, J, Ehrenberg, A, Östling, J, Cleach, I, Mège, J-L, Vitte, J, Aina, R, Dubiela, P, Pfeifer, S, Bublin, M, Radauer, C, Humeniuk, P, Kabasser, S, Asero, R, Bogas, G, Gomez, F, Campo, P, Salas, M, Doña, I, Barrionuevo, E, Guerrero, MA, Mayorga, C, Prieto, A, Barber, D, Torres, MJ, Jamin, A, Wangorsch, A, Ballmer, B, Vieths, S, Scheurer, S, Apostolovic, D, Mihailovic, J, Krstic, M, Starkhammar, M, Velickovic, TC, Hamsten, C, van Hage, M, van Erp, FC, Knol, EF, Kansen, HM, Pontoppidan, B, Meijer, Y, van der Ent, CK, Knulst, AC, Sayers, R, Brown, H, Custovic, A, Simpson, A, Mills, C, Schulz, J, Akkerdaas, J, Totis, M, Capt, A, Herouet-Guicheney, C, van Ree, R, Banerjee, T, Banerjee, A, Claude, M, Bouchaud, G, Lupi, R, Castan, L, Tranquet, O, Denery-Papini, S, Bodinier, M, Brossard, C, De Poi, R, Gritti, E, De Dominicis, E, Popping, B, de Laureto, PP, Palosuo, K, Kukkonen, AK, Pelkonen, A, Mäkelä, M, Lee, NA, Rost, J, Muralidharan, S, Campbell, D, Mehr, S, Nock, C, Baumert, J, Taylor, S, Mastrorilli, C, Tripodi, S, Caffarelli, C, Perna, S, Di Rienzo Businco, A, Sfika, I, Dondi, A, Bianchi, A, Dascola, CP, Ricci, G, Cipriani, F, Maiello, N, del Giudice, MM, Frediani, T, Frediani, S, Macrì, F, Pistoletti, C, Iacono, ID, Patria, MF, Varin, E, Peroni, D, Comberiati, P, Chini, L, Moschese, V, Lucarelli, S, Bernardini, R, Pingitore, G, Pelosi, U, Olcese, R, Moretti, M, Cirisano, A, Faggian, D, Travaglini, A, Plebani, M, Verga, MC, Calvani, M, Giordani, P, Matricardi, PM, Ontiveros, N, Cabrera-Chavez, F, Galand, J, Beaudouin, E, Pineau, F, Sakai, S, Matsunaga, K, Teshima, R, Larré, C, Denery, S, Tschirner, S, Trendelenburg, V, Schulz, G, Niggemann, B, Beyer, K, Bouferkas, Y, Belabbas, Y, Saidi, D, Kheroua, O, Mecherfi, KEE, Guendouz, M, Haddi, A, Kaddouri, H, Amaral, L, Pereira, A, Rodrigues, S, Datema, M, Jongejan, L, Clausen, M, Knulst, A, Papadopoulos, N, Kowalski, M, de Blay, F, Zwinderman, A, Hoffman-Sommergruber, K, Ballmer-Weber, B, Fernandez-Rivas, M, Deng, S, Yin, J, Eisenmann, C, Nassiri, M, Reinert, R, van der Valk, JPM, van Wijk, RG, Vergouwe, Y, Steyerberg, EW, Reitsma, M, Wichers, HJ, Savelkoul, HFJ, Vlieg-Boerstra, B, Dubois, AEJ, Carolino, F, Rodolfo, A, Cernadas, J, Roa-Medellín, D, Rodriguez-Fernandez, A, Navarro, J, Albendiz, V, Baeza, ML, Intente-Herrero, S, Mikkelsen, A, Mehlig, K, Lissner, L, Verrill, L, Luccioli, S, van Bilsen, J, Kuper, F, Wolterbeek, A, Rankouhi, TR, Verschuren, L, Cnossen, H, Jeurink, P, Garssen, J, Knippels, L, Garthoff, J, Houben, G, Leeman, W, Eleonore Pettersson, M, Schins, AMM, Koppelman, GH, Kollen, BJ, Zubchenko, S, Kuntz, S, Mérida, P, Álvaro, M, Riggioni, C, Castellanos, JH, Jimenez, R, Cap, M, Drumez, E, Lejeune, S, Thumerelle, C, Mordacq, C, Nève, V, Ricò, S, Varini, M, Nocerino, R, Cosenza, L, Amoroso, A, Di Costanzo, M, Di Scala, C, Bedogni, G, Canani, RB, Turner, PJ, Poza-Guedes, P, González-Pérez, R, Sánchez-Machín, I, Matheu-Delgado, V, Wambre, E, Ballegaard, A-S, Madsen, C, Gregersen, J, Bøgh, KL, Aubert, P, Neunlist, M, Magnan, A, Lozano-Ojalvo, D, Pablos-Tanarro, A, Pérez-Rodríguez, L, Molina, E, López-Fandiño, R, Rekima, A, Macchiaverni, P, Turfkruyer, M, Holvoet, S, Dupuis, L, Baiz, N, Annesi-Maesano, I, Mercenier, A, Nutten, S, Verhasselt, V, Mrakovcic-Sutic, I, Banac, S, Sutic, I, Baricev-Novakovic, Z, Pavisic, V, Muñoz-Cano, R, Jiménez-Rodríguez, T, Corbacho, D, Roca-Ferrer, J, Bartra, J, Bulog, A, Micovic, V, Markiewicz, L, Szymkiewicz, A, Szyc, A, Wróblewska, B, Harvey, BM, Harthoorn, LF, Wesley Burks, A, Rentzos, G, Björk, A-LB, Bengtsson, U, Barber, C, Kalicinsky, C, Breynaert, C, Coorevits, L, Jansen, C, Van Hoeyveld, E, Verbeke, K, Kochuyt, A-M, Schrijvers, R, Deleanu, D, Muntean, A, Konstantakopoulou, M, Pasioti, M, Papadopoulou, A, Iliopoulou, A, Mikos, N, Kompoti, E, de Castro, ED, Bartalomé, B, Ue, KL, Griffiths, E, Till, S, Grimshaw, K, Roberts, G, Selby, A, Butiene, I, Larco, JI, Dubakiene, R, Fiandor, A, Fiocchi, A, Sigurdardottir, S, Sprikkelman, A, Schoemaker, A-F, Xepapadaki, P, Keil, T, Cojocariu, Z, Barbado, BS, Iancu, V, Arroabarren, E, Esarte, MG, Arteaga, M, Andrade, MC, Borges, D, Kalil, J, Bianchi, PG, Agondi, RC, Gupta, RK, Sharma, A, Gupta, K, Das, M, Dwivedi, P, Karseladze, R, Jorjoliani, L, Saginadze, L, Tskhakaia, M, Basello, K, Piuri, G, Speciani, AF, Speciani, MC, Camerotto, C, Zinno, F, Pakholchuk, O, Nedelska, S, Pattini, S, Costantino, MT, Peveri, S, Villalta, D, Savi, E, Costanzi, A, Revyakina, VA, Kiseleva, MA, Kuvshinova, ED, Larkova, IA, Shekhetov, AA, Silva, D, Moreira, A, Plácido, J, van der Kleij, H, van Twuijver, E, Sutorius, R, de Kam, P-J, van Odijk, J, Lindqvist, H, Lustig, E, Jácome, AAA, Aguilar, KLB, Domínguez, MG, Hernández, DAM, Caruso, C, Casale, C, Rapaccini, GL, Romano, A, De Vitis, I, Cocco, RR, Aranda, C, Mallozi, MC, Motta, JF, Moraes, L, Pastorino, A, Rosario, N, Goudouris, E, Porto, A, Wandalsen, NF, Sarinho, E, Sano, F, Solé, D, Pitsios, C, Petrodimopoulou, M, Papadopoulou, E, Passioti, M, Kontogianni, M, Adamia, N, Khaleva, E, del Prado, AP, Du Toit, G, Krzych, E, Samolinska-Zawisza, U, Furmanczyk, K, Tomaszewska, A, Raciborski, F, Lipiec, A, Samel-Kowalik, P, Walkiewicz, A, Borowicz, J, Samolinski, B, Nano, AL, Recto, M, Somoza, ML, López, NB, Alzate, DP, Ruano, FJ, Garcimartín, MI, Haroun, E, de la Torre, MV, Rojas, A, Onieva, ML, Canto, G, Rodrigues, A, Forno, A, Cabral, AJ, Gonçalves, R, Vorozhko, I, Sentsova, T, Chernyak, O, Denisova, S, Ilènko, L, Muhortnich, V, Zimmermann, C, Rohrbach, A, Bakhsh, FR, Boudewijn, K, Oomkes-Pilon, A-M, Van Ginkle, D, Šilar, M, Jeverica, A, Vesel, T, Avčin, T, Korošec, P, van der Valk, J, Berends, I, Arends, N, van Maaren, M, Wichers, H, Emons, J, Dubois, A, de Jong, N, Matsyura, O, Besh, L, Huang, C-H, Jan, T-R, Stiefel, G, Tratt, J, Kirk, K, Arasi, S, Caminiti, L, Crisafulli, G, Fiamingo, C, Fresta, J, Pajno, G, Remington, B, Kruizinga, A, Marty Blom, W, Westerhout, J, Bijlsma, S, Blankestijn, M, Otten, H, Klemans, R, Michelsen-Huisman, AD, van Os-Medendorp, H, Kruizinga, AG, Versluis, A, van Duijn, G, de Zeeuw-Brouwer, HM-L, Castenmiller, JJM, Noteborn, HPJM, Houben, GF, Bravin, K, Luyt, D, Javed, B, Couch, P, Munro, C, Padfield, P, Sperrin, M, Byrne, A, Oosthuizen, L, Kelleher, C, Ward, F, Brosnan, N, King, G, Corbet, E, Guzmán, JAH, García, MB, Asensio, O, Navarrete, LV, Larramona, H, Miró, XD, Pyrz, K, Austin, M, Boloh, Y, Galloway, D, Hernandez, P, Hourihane, JOB, Kenna, F, Majkowska-Wojciechowska, B, Regent, L, Themisb, M, Schnadt, S, Semic-Jusufagic, A, Galvin, AD, Kauppila, T, Kuitunen, M, Kitsioulis, NA, Douladiris, N, Kostoudi, S, Manolaraki, I, Mitsias, D, Manousakis, E, Papadopoulos, NG, Knibb, R, Hammond, J, Cooke, R, Yrjänä, J, Hanni, A-M, Vähäsarja, P, Mustonen, O, Dunder, T, Kulmala, P, Lasa, E, D’Amelio, C, Martínez, S, Joral, A, Gastaminza, G, Goikoetxea, MJ, Candy, DCA, Van Ampting, MTJ, Oude Nijhuis, MM, Butt, AM, Peroni, DG, Fox, AT, Knol, J, Michaelis, LJ, Padua, I, Padrao, P, Moreira, P, Barros, R, Sharif, H, Ahmed, M, Gomaa, N, Mens, J, Smit, K, Timmermans, F, Poredoš, T, Jeverica, AK, Sedmak, M, Benedik, E, Accetto, M, Zupančič, M, Yonamine, G, Soldateli, G, Aquilante, B, Pastorino, AC, de Moraes Beck, CL, Gushken, AK, de Barros Dorna, M, dos Santos, CN, Castro, APM, Al-Qahtani, A, Arnaout, R, Khaliq, AR, Amin, R, Sheikh, F, Alvarez, J, Anda, M, Palacios, M, De Prada, M, Ponce, C, Balbino, B, Sibilano, R, Marichal, T, Gaudenzio, N, Karasuyama, H, Bruhns, P, Tsai, M, Reber, LL, Galli, SJ, Ferreira, AR, Cernadas, JR, del Campo García, A, Fernández, SP, Carrera, NS, Sánchez-Cruz, FB, Lorenzo, JRF, Claus, S, Pföhler, C, Ruëff, F, Treudler, R, Jaume, ME, Madroñero, A, Perez, MTG, Julia, JC, Plovdiv, CH, Gethings, L, Langridge, J, Adel-Patient, K, Bernard, H, Barcievic-Jones, I, Sokolova, R, Yankova, R, Ivanovska, M, Murdjeva, M, Popova, T, Dermendzhiev, S, Karjalainen, M, Lehnigk, U, Brown, D, Locklear, JC, Locklear, J, Maris, I, Hourihane, J, Ornelas, C, Caiado, J, Ferreira, MB, Pereira-Barbosa, M, Puente, Y, Daza, JC, Monteseirin, FJ, Ukleja-Sokolowska, N, Gawronska-Ukleja, E, Zbikowska-Gotz, M, Bartuzi, Z, Sokolowski, L, Adams, A, Mahon, B, English, K, Gourdon-Dubois, N, Sellam, L, Pereira, B, Michaud, E, Messaoudi, K, Evrard, B, Fauquert, J-L, Palomares, F, Gomez, G, Rodriguez, MJ, Galindo, L, Molina, A, Paparo, L, Mennini, M, Aitoro, R, Wawrzeńczyk, A, Przybyszewski, M, Sarıcoban, HE, Ugras, M, Yalvac, Z, Flokstra-de Blok, BMJ, van der Velde, JL, Vereda, A, Ippolito, C, Traversa, A, Adriano, D, Bianchi, DM, Gallina, S, Decastelli, L, Makatsori, M, Miles, A, Devetak, SP, Devetak, I, Tabet, SA, Trandbohus, JF, Winther, P, Malling, H-J, Hansen, KS, Garvey, LH, Wang, C-C, Cheng, Y-H, Tung, C-W, Dietrich, M, Marenholz, I, Kalb, B, Grosche, S, Blümchen, K, Schlags, R, Price, M, Rietz, S, Esparza-Gordillo, J, Lau, S, Lee, Y-A, Almontasheri, A, Bahkali, MA, Elshorbagi, S, Alfhaid, A, Altamimi, M, Madbouly, E, Al-Dhekri, H, Arnaout, RK, Basagaña, M, Miquel, S, Bartolomé, B, Brix, B, Rohwer, S, Brandhoff, S, Berger, A, Suer, W, Weimann, A, Bueno, C, Martín-Pedraza, L, Abián, S, Segundo-Acosta, PS, López-Rodríguez, JC, Barderas, R, Batanero, E, Cuesta-Herranz, J, Villalba, MT, Correia, M, Benito-Garcia, F, Arêde, C, Piedade, S, Morais-Almeida, M, Hindley, J, Yarham, R, Kuklinska-Pijanka, A, Gillick, D, Patient, K, Chapman, MD, Miranda, A, Matos, E, Sokolova, A, Rao, H, Baricevic-Jones, I, Smith, F, Xue, W, Magnusdottir, H, Vidarsdottir, AG, Lund, S, Jensen, AB, Ludviksson, BR, Simon, R, Elfont, R, Bennett, S, Voyksner, R, de Lurdes Torre, M, Yürek, S, Faber, MA, Bastiaensen, A, Mangodt, E, van Gasse, A, Decuyper, I, Sabato, V, Hagendorens, MM, Bridts, CH, De Clerck, LS, Ebo, D, Schwarz, S, Ziegert, M, Albroscheit, S, Schwager, C, Kull, S, Behrends, J, Röckendorf, N, Schocker, F, Frey, A, Homann, A, Becker, W-M, Jappe, U, Zaabat, N, Osscini, S, Agabriel, C, Sterling, B, Carsin, A, Liabeuf, V, Maćków, M, Zbróg, A, Bronkowska, M, Courtois, J, Gadisseur, R, Bertholet, C, Lukas, P, Cavalier, E, Delahaut, P, Quinting, B, Gertmo, MB, Hasseus, ET, Barzylovych, V, Oliveira, J, Ensina, LF, Aranda, CS, Dopazo, L, Lopez, R, Perez, R, Santos-Diez, L, Bilbao, A, Garcia, JM, Núñez, IG, Mármol, MÁA, Villarejo, MJB, Martos, JAB, Vergara, MS, García, JMI, Michalska, A, Sergiejko, G, Zacniewski, R, Ghiordanescu, I-M, Deaconu, C, Popescu, M, Bumbacea, RS, Ibranji, A, Nikolla, E, Loloci, G, Juel-Berg, N, Larsen, LF, Poulsen, LK, Marcelino, J, Prata, R, Costa, AC, Duarte, F, Neto, M, Santos, J, Pestana, LC, Sampaio, D, Minale, P, Dignetti, P, Bignardi, D, Nedelea, I, Popescu, F-D, Vieru, M, Secureanu, F-A, Ganea, CS, Vieira, M, Silva, JPM, Watts, T, Watts, S, Lomikovska, M, Peredelskaya, M, Nenasheva, N, Filipovic, I, Zivkovic, Z, Filipovic, D, Higgs, J, Warner, A, and Jones, C

Published
2017

23. Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

Author

Bøgh KL van Bilsen J Glogowski R López-Expósito I Bouchaud G Blanchard C Bodinier M Smit J P

Abstract

Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet such as newly developed innovative foods or foods produced using new technologies and production processes insects algae duckweed or agricultural products from third countries creates the opportunity for development of new food allergies and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However although various animal models have been proposed for this purpose to date none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here the design of various animal models are reviewed including among others considerations of species and strain diet route of administration dose and formulation of the test protein relevant controls and endpoints measured.

Published
2016
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24. Comparison of IgE-binding epitopes on wheat gliadins for patients with food allergy and experimentally sensitized mice

Author

Bodinier, M., Denery, S., Pineau, F., Triballeau, S., Leroy, M., Tranquet, O., Adel-Patient, K., Moneret-Vautrin, D., Bakan, B., Didier MARION, Lelion, A., Mothes, T., Mameri, H., Kasarda, D., Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Unité de Recherche Immuno-Allergie Alimentaire, Université Nancy 2, Institute for Laboratory Medicine, Otto Wagner Hospital Vienna, Agricultural Research Service , US Department of Agriculture, Dairy Forage Research Center, The European Academy of Allergy and Clinical Immunology (EAACI). Zurich, CHE., and ProdInra, Migration

Subjects
food allergy, wheat allergic patients, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, wheat, food and beverages, mouse model of allergy, epitopes, gliadins, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Mice models of allergy to wheat proteins have been recently developed but have not been characterized for epitope pattern. In our laboratory, mice were sensitized with total gliadins and produced IgE antibodies that recognize the different gliadin classes :α,β,γ, *1,2 and *5. The relevance of this mouse model has to be evaluated regarding IgE-binding epitopes. The aim of the study is to compare B-cell epitopes in wheat allergic patients and sensitized mice in order to find out whether IgE antibodies elicited in mice are representative of human ones.

Published
2011

34. MHC-peptide multimers: tools of choice for detecting and sorting antigen-specific T-cells.

Author

Lang, François, Bodinier, Marie, Lang, F, and Bodinier, M

Subjects
MAJOR histocompatibility complex, PEPTIDES, T cells, ANTIGENS, CELL receptors, HISTOCOMPATIBILITY antigens, DIMERIZATION
Abstract

Examines the role of major histocompatibility cell (MHC)-peptide multimers as tools of choice for detecting and sorting antigen-specific T-cells. Generation of MHC tetramers; Detection of antigen-specific T cells with tetramers; sorting specific T cells with MHC multimers.

Published
2001
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35. A Gestational Supplementation With 2′‐Fucosyllactose Is an Effective Strategy to Prevent Food Allergy.

Author

Rousseaux, A., Misme‐Aucouturier, B., Le Romancer, M., Villette, R., Larsen, M., De Carvalho, M., Bouchaud, G., Perrin, E., Barbarot, S., Brosseau, C., and Bodinier, M.

Subjects
*BIOLOGICAL systems, *FOOD allergy, *MEDITERRANEAN diet, *AMNIOTIC liquid, *BREAST milk, *MILK allergy
Abstract

The article discusses a study on the effectiveness of gestational supplementation with 2'-Fucosyllactose (2'-FL) in preventing food allergies in offspring. The study found that maternal diet during pregnancy and breastfeeding can impact the immune system, gut microbiota, and epithelial barriers, leading to allergies. The research showed that gestational supplementation with 2'-FL protected offspring from food allergies by creating a specific microbial and immune imprint. This study highlights the potential benefits of maternal nutrition and supplementation in preventing allergies in children, suggesting further research in high-risk populations. [Extracted from the article]

Published
2024
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36. From Hit to Lead. Combining Two Complementary Methods for Focused Library Design. Application to μ Opiate Ligands

Author

Poulain, R., Horvath, D., Bonnet, B., Eckhoff, C., Chapelain, B., Bodinier, M.-C., and Deprez, B.

Abstract

Compound 1 obtained by random screening and displaying a micromolar activity on the μ opiate receptor was chosen as a starting point for optimization. Two complementary concepts of similarity were used for the design of analogues and compared. These are based, respectively, on a computer-aided comparison of pharmacophoric patterns and on topological similarity. The structure−activity relationships are discussed in light of both similarity concepts. Compound 40, an N-methyl-3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decyl)acetamide derivative, designed by combining the structure−activity relationships enlightened by each method, has a subnanomolar affinity for μ (h) receptor (IC50 = 0.9 nM). It is a promising lead, allowing the design of a new series of analogues substituted at the N-3 of the spirocycle moiety.

Published
2001

37. From Hit to Lead. Analyzing Structure−Profile Relationships

Author

Poulain, R., Horvath, D., Bonnet, B., Eckhoff, C., Chapelain, B., Bodinier, M.-C., and Deprez, B.

Abstract

Two compounds, obtained by random screening, and displaying micromolar activities on the μ opiate receptor were used as starting points for optimization. In that work, the traditional concept of the activity of a compound (related to one or a few targets) was extended to the comprehensive pharmacological profile of that compound on more than 70 receptors, transporters, and channels relevant to a CNS-oriented project. Using the two complementary design strategies based on two similarity concepts described in the previous paper, we have obtained analogues with IC50 values ranging between 0.9 nM and a few micromolar on the μ receptor and displaying qualitatively different profiles. We discuss here, both on a case-by-case basis and from a statistical standpoint, the pharmacological profiles in light of the two similarity concepts.

Published
2001

39. Selection and long-term persistence of reactive CTL clones during an EBV chronic response are determined by avidity, CD8 variable contribution compensating for differences in TCR affinities

Author

Couedel, C., Bodinier, M., Peyrat, Ma, Bonneville, M., Davodeau, F., and françois LANG

Subjects
Adult, Cytotoxicity, Immunologic, Herpesvirus 4, Human, Alanine, Macromolecular Substances, CD8 Antigens, Receptors, Antigen, T-Cell, alpha-beta, Molecular Sequence Data, Immunology, Clone Cells, DNA-Binding Proteins, Major Histocompatibility Complex, Viral Proteins, Amino Acid Substitution, Trans-Activators, Humans, Immunology and Allergy, Female, Amino Acid Sequence, Peptides, T-Lymphocytes, Cytotoxic
Abstract

Recent studies have suggested that the diversity of TCR repertoire after primary immunization is conserved in memory T cells and that a progressive narrowing of this repertoire may take place during recall infections. It now remains to be investigated which parameters determine the repertoire of the memory response and possibly restrict its diversity after subsequent antigenic challenges. To address this question, we took advantage of a panel of CD8+ T cell clones from the joint of a rheumatoid arthritis patient and selected for their reactivity against a single MHC/peptide complex. Characterization of both TCR chains documented a great diversity among those clones and the persistence of clonotypes over a 2-yr period. Strikingly, despite the observed repertoire heterogeneity, all clones displayed a narrow range of MHC/peptide density requirements in cytotoxicity assays (ED50 between 9 and 36 nM). TCR affinities were then indirectly estimated by blocking CD8 interaction with an anti-CD8 mAb. We found a wide range of TCR affinities among the different clonotypes that segregated with Vβ usage. We thus propose that during an in vivo chronic response, a narrow range of avidity of the TCR-CD8 complex conditions long-term clonotype persistence, and that the level of CD8 contribution is adjusted to keep clonotypes with variable TCR affinities within this avidity window.

40. Integrated clustering of multiple immune marker trajectories reveals different immunotypes in severely injured patients.

Author

Bodinier M, Peronnet E, Llitjos JF, Kreitmann L, Brengel-Pesce K, Rimmelé T, Fleurie A, Textoris J, Venet F, Maucort-Boulch D, and Monneret G

Subjects
Humans, Male, Female, Middle Aged, Adult, Cluster Analysis, Critical Illness, Intensive Care Units statistics & numerical data, Intensive Care Units organization & administration, Aged, Sepsis blood, Sepsis immunology, Longitudinal Studies, Biomarkers blood, Biomarkers analysis, Wounds and Injuries immunology, Wounds and Injuries blood
Abstract

Background: The immune response of critically ill patients, such as those with sepsis, severe trauma, or major surgery, is heterogeneous and dynamic, but its characterization and impact on outcomes are poorly understood. Until now, the primary challenge in advancing our understanding of the disease has been to concurrently address both multiparametric and temporal aspects., Methods: We used a clustering method to identify distinct groups of patients, based on various immune marker trajectories during the first week after admission to ICU. In 339 severely injured patients, we initially longitudinally clustered common biomarkers (both soluble and cellular parameters), whose variations are well-established during the immunosuppressive phase of sepsis. We then applied this multi-trajectory clustering using markers composed of whole blood immune-related mRNA., Results: We found that both sets of markers revealed two immunotypes, one of which was associated with worse outcomes, such as increased risk of hospital-acquired infection and mortality, and prolonged hospital stays. This immunotype showed signs of both hyperinflammation and immunosuppression, which persisted over time., Conclusion: Our study suggest that the immune system of critically ill patients can be characterized by two distinct longitudinal immunotypes, one of which included patients with a persistently dysregulated and impaired immune response. This work confirms the relevance of such methodology to stratify patients and pave the way for further studies using markers indicative of potential immunomodulatory drug targets., (© 2024. The Author(s).)

Published
2024
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41. Immune profiling of critically ill patients with acute kidney injury during the first week after various types of injuries: the REALAKI study.

Author

Bidar F, Peillon L, Bodinier M, Venet F, Monneret G, Lukaszewicz AC, Llitjos JF, Textoris J, and Rimmelé T

Subjects
Humans, Male, Female, Middle Aged, Aged, Adult, Cohort Studies, Intensive Care Units statistics & numerical data, Intensive Care Units organization & administration, Wounds and Injuries complications, Wounds and Injuries immunology, Prospective Studies, Time Factors, Biomarkers blood, Biomarkers analysis, Sepsis complications, Sepsis immunology, Acute Kidney Injury immunology, Acute Kidney Injury etiology, Critical Illness
Abstract

Background: Acute kidney injury (AKI) is common in hospitalized patients and results in significant morbidity and mortality. The objective of the study was to explore the systemic immune response of intensive care unit patients presenting with AKI, especially the association between immune profiles and persistent AKI during the first week after admission following various types of injuries (sepsis, trauma, surgery, and burns)., Methods: REALAKI is an ancillary analysis of the REAnimation Low Immune Status Marker (REALISM) cohort study, in which 359 critically ill patients were enrolled in three different intensive care units. Patients with end-stage renal disease were excluded from the REALAKI study. Clinical samples and data were collected three times after admission: at day 1 or 2 (D1-2), day 3 or 4 (D3-4) and day 5, 6 or 7 (D5-7). Immune profiles were compared between patients presenting with or without AKI. Patients with AKI at both D1-2 and D5-7 were defined as persistent AKI. A multivariable logistic regression model was performed to determine the independent association between AKI and patients' immunological parameters., Results: Three hundred and fifty-nine patients were included in this analysis. Among them, 137 (38%) were trauma patients, 103 (29%) post-surgery patients, 95 (26%) sepsis patients, and 24 (7%) were burn patients. One hundred and thirty-nine (39%) patients presented with AKI at D1-2 and 61 (20%) at D5-7. Overall, 94% presented with persistent AKI at D5-7. Patients with AKI presented with increased pro and anti-inflammatory cytokines and altered innate and adaptive immune responses. The modifications observed in the immune profiles tended to be more pronounced with increasing KDIGO stages. In the logistic regression model, a statistically significant association was observed at D1-2 between AKI and CD10 low CD16 low immature neutrophils (OR 3.03 [1.7-5.5]-p < 0.001). At D5-7, increased interleukin-10 (IL-10) levels and reduced ex vivo TNF-α production after LPS stimulation were significantly associated with the presence of AKI (OR 1.38 [1.12-1.71]-p = 0.001 and 0.51 [0.27-0.91]-p = 0.03, respectively). Patients who recovered from AKI between D1-2 and D5-7 compared to patients with persistent AKI at D5-7, tended to correct these alterations., Conclusion: Following various types of severe injuries, early AKI is associated with the initial inflammatory response. Presence of AKI at the end of the first week after injury is associated with injury-induced immunosuppression., (© 2024. The Author(s).)

Published
2024
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42. Use of Immune Profiling Panel to assess the immune response of septic patients for prediction of worsening as a composite endpoint.

Author

Peronnet E, Terraz G, Cerrato E, Imhoff K, Blein S, Brengel-Pesce K, Bodinier M, Fleurie A, Rimmelé T, Lukaszewicz AC, Monneret G, and Llitjos JF

Subjects
Humans, Male, Female, Aged, Middle Aged, Machine Learning, Retrospective Studies, Prognosis, Sepsis immunology, Biomarkers
Abstract

Sepsis induces intense, dynamic and heterogeneous host response modulations. Despite improvement of patient management, the risk of mortality and healthcare-associated infections remains high. Treatments to counterbalance immune response are under evaluation, but effective biomarkers are still lacking to perform patient stratification. The design of the present study was defined to alleviate the limitations of existing literature: we selected patients who survived the initial hyperinflammatory response and are still hospitalized at day 5-7 after ICU admission. Using the Immune Profiling Panel (IPP), a fully automated RT-qPCR multiplex prototype, we optimized a machine learning model combining the IPP gene expression levels for the identification of patients at high risk of worsening, a composite endpoint defined as death or secondary infection, within one week after sampling. This was done on 332 sepsis patients selected from two retrospective studies. The IPP model identified a high-risk group comprising 30% of patients, with a significant increased proportion of worsening events at day 28 compared to the low-risk group (49% vs. 28%, respectively). These preliminary results underline the potential clinical application of IPP for sepsis patient stratification in a personalized medicine perspective, that will be confirmed in a larger prospective multicenter study., (© 2024. The Author(s).)

Published
2024
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43. Persistent NLRP3 inflammasome activation is associated with delayed immunosuppression in septic patients.

Author

Coudereau R, Bodinier M, Lukaszewicz AC, Py BF, Argaud L, Cour M, Bidar F, Cerrato E, Garnier L, Gossez M, Venet F, and Monneret G

Subjects
Humans, Immunosuppression Therapy, Interleukin-1beta genetics, NLR Family, Pyrin Domain-Containing 3 Protein genetics, Inflammasomes genetics, Sepsis genetics
Abstract

Sepsis triggers a complex response marked by the simultaneous presence of proinflammatory and immunosuppressive elements, disrupting the mechanisms intended to maintain homeostasis. While the NLRP3 inflammasome has been demonstrated to contribute to the inflammatory side, its connection with delayed sepsis-induced immunosuppression remains unexplored. The present objective was to concomitantly and prospectively assess NLRP3 activation (IL-1β, IL-18, and soluble receptors) and features of immune failure (IL-10, mHLA-DR, myeloid-derived suppressor cells) in septic patients. To validate our findings, we conducted a transcriptomic analysis of mRNA of NLRP3-related genes (IL-18R1, IL-1R2) on an additional cohort of 107 patients. Two distinct endotypes were identified. One cluster displayed moderate inflammation rapidly returning to normal values, while the other exhibited a higher inflammatory response persisting until day 28, which was associated with persistent marked immunosuppression and higher 28-d mortality. Identifying endotypes with different pro/anti-inflammatory trajectories could hold important clinical implications for the management of sepsis., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2024
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44. Tolerance to heated egg in egg allergy: Explanations and implications for prevention and treatment.

Author

Leau A, Denery-Papini S, Bodinier M, and Dijk W

Abstract

Hen's egg allergy is the second most frequent food allergy found in children. Allergic symptoms can be caused by raw or heated egg, but a majority of egg-allergic children can tolerate hard-boiled or baked egg. Understanding the reasons for the tolerance towards heated egg provides clues about the molecular mechanisms involved in egg allergy, and the differential allergenicity of heated and baked egg might be exploited to prevent or treat egg allergy. In this review, we therefore discuss (i) why some patients are able to tolerate heated egg; by highlighting the structural changes of egg white (EW) proteins upon heating and their impact on immunoreactivity, as well as patient characteristics, and (ii) to what extent heated or baked EW might be useful for primary prevention strategies or oral immunotherapy. We describe that the level of immunoreactivity towards EW helps to discriminate patients tolerant or reactive to heated or baked egg. Furthermore, the use of heated or baked egg seems effective in primary prevention strategies and might limit adverse reactions. Oral immunotherapy is a promising treatment strategy, but it can sometimes cause significant adverse events. The use of heated or baked egg might limit these, but current literature is insufficient to conclude about its efficacy., (© 2023 The Authors. Clinical and Translational Allergy published by John Wiley and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Published
2023
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45. Identification of a sub-group of critically ill patients with high risk of intensive care unit-acquired infections and poor clinical course using a transcriptomic score.

Author

Bodinier M, Monneret G, Casimir M, Fleurie A, Conti F, Venet F, Cazalis MA, Cerrato E, Peronnet E, Rimmelé T, Lukaszewicz AC, Brengel-Pesce K, and Llitjos JF

Subjects
Humans, Retrospective Studies, Critical Illness, Intensive Care Units, Disease Progression, Transcriptome, Sepsis diagnosis, Sepsis genetics
Abstract

Background: The development of stratification tools based on the assessment of circulating mRNA of genes involved in the immune response is constrained by the heterogeneity of septic patients. The aim of this study is to develop a transcriptomic score based on a pragmatic combination of immune-related genes detected with a prototype multiplex PCR tool., Methods: As training cohort, we used the gene expression dataset obtained from 176 critically ill patients enrolled in the REALISM study (NCT02638779) with various etiologies and still hospitalized in intensive care unit (ICU) at day 5-7. Based on the performances of each gene taken independently to identify patients developing ICU-acquired infections (ICU-AI) after day 5-7, we built an unweighted score assuming the independence of each gene. We then determined the performances of this score to identify a subgroup of patients at high risk to develop ICU-AI, and both longer ICU length of stay and mortality of this high-risk group were assessed. Finally, we validated the effectiveness of this score in a retrospective cohort of 257 septic patients., Results: This transcriptomic score (TScore) enabled the identification of a high-risk group of patients (49%) with an increased rate of ICU-AI when compared to the low-risk group (49% vs. 4%, respectively), with longer ICU length of stay (13 days [95% CI 8-30] vs. 7 days [95% CI 6-9], p < 0.001) and higher ICU mortality (15% vs. 2%). High-risk patients exhibited biological features of immune suppression with low monocytic HLA-DR levels, higher immature neutrophils rates and higher IL10 concentrations. Using the TScore, we identified 160 high-risk patients (62%) in the validation cohort, with 30% of ICU-AI (vs. 18% in the low-risk group, p = 0.06), and significantly higher mortality and longer ICU length of stay., Conclusions: The transcriptomic score provides a useful and reliable companion diagnostic tool to further develop immune modulating drugs in sepsis in the context of personalized medicine., (© 2023. The Author(s).)

Published
2023
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46. Distinct Immune Reconstitution Profiles Captured by Immune Functional Assays at 6 Months Post Allogeneic Hematopoietic Stem Cell Transplantation.

Author

Mouton W, Conrad A, Alcazer V, Boccard M, Bodinier M, Oriol G, Subtil F, Labussière-Wallet H, Ducastelle-Lepretre S, Barraco F, Balsat M, Fossard G, Brengel-Pesce K, Ader F, and Trouillet-Assant S

Subjects
Humans, Transplantation, Homologous, Cross-Sectional Studies, Immunophenotyping, Immune Reconstitution, Hematopoietic Stem Cell Transplantation
Abstract

Immune reconstitution after allogeneic-hematopoietic-stem-cell transplantation (allo-HSCT) is a complex and individual process. In this cross-sectional study, whole-blood (WB) immune functional assay (IFA) was used to characterize immune function by assessing immune-related gene/pathway alterations. The usefulness of this tool in the context of infection, 6 months after transplantation, was evaluated. Sixty allo-HSCT recipients at 6 months after transplantation and 10 healthy volunteers (HV) were included. WB was stimulated in standardized TruCulture tubes using lipopolysaccharides and Staphylococcal enterotoxin B. Gene expression was quantified using a custom 144-gene panel using NanoString nCounter technology and analyzed using Ingenuity Pathway Analysis. The relationships between immune function and clinical characteristics, immune cell counts, and post-transplantation infections were assessed. Allo-HSCT recipients were able to activate similar networks of the innate and adaptive immune response compared to HV, with, nevertheless, a lower intensity. A reduced number and a lower expression of genes associated with immunoregulatory and inflammatory processes were observed in allo-HSCT recipients. The use of immunosuppressive treatments was associated with a protracted immune reconstitution revealed by transcriptomic immunoprofiling. No difference in immune cell counts was observed among patients receiving or not receiving immunosuppressive treatments using a large immunophenotyping panel. Moreover, the expression of a set of genes, including CCL3/CCL4, was significantly lower in patients with Herpesviridae reactivation (32%, 19/60), which once again was not identified using classical immune cell counts. Transcriptional IFA revealed the heterogeneity among allo-HSCT recipients with a reduced immune function, a result that could not be captured by circulating immune cell counts. This highlights the potential added value of this tool for the personalized care of immunocompromised patients., Competing Interests: Conflict of interest statement K.B.P., G.O., and M.Bod are employees of bioMérieux SA., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Published
2023
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47. Immunomodulation of B Lymphocytes by Prebiotics, Probiotics and Synbiotics: Application in Pathologies.

Author

Rousseaux A, Brosseau C, and Bodinier M

Subjects
Animals, Humans, Prebiotics, Immunomodulation, B-Lymphocytes, Macrophages, Synbiotics, Probiotics pharmacology
Abstract

Introduction: Prebiotics, probiotics and synbiotics are known to have major beneficial effects on human health due to their ability to modify the composition and the function of the gut mucosa, the gut microbiota and the immune system. These components largely function in a healthy population throughout different periods of life to confer homeostasis. Indeed, they can modulate the composition of the gut microbiota by increasing bacteria strands that are beneficial for health, such as Firmicute and Bifidobacteria , and decreasing harmful bacteria, such as Enteroccocus . Their immunomodulation properties have been extensively studied in different innate cells (dendritic cells, macrophages, monocytes) and adaptive cells (Th, Treg, B cells). They can confer a protolerogenic environment but also modulate pro-inflammatory responses. Due to all these beneficial effects, these compounds have been investigated to prevent or to treat different diseases, such as cancer, diabetes, allergies, autoimmune diseases, etc. Regarding the literature, the effects of these components on dendritic cells, monocytes and T cells have been studied and presented in a number of reviews, but their impact on B-cell response has been less widely discussed., Conclusions: For the first time, we propose here a review of the literature on the immunomodulation of B-lymphocytes response by prebiotics, probiotics and synbiotics, both in healthy conditions and in pathologies., Discussion: Promising studies have been performed in animal models, highlighting the potential of prebiotics, probiotics and synbiotics intake to treat or to prevent diseases associated with B-cell immunomodulation, but this needs to be validated in humans with a full characterization of B-cell subsets and not only the humoral response.

Published
2023
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48. Maternal prebiotic supplementation impacts colitis development in offspring mice.

Author

Lê A, Selle A, Aubert P, Durand T, Brosseau C, Bordron P, Delage E, Chaffron S, Petitfils C, Cenac N, Neunlist M, Bodinier M, and Rolli-Derkinderen M

Abstract

Background and Aims: Maternal diet plays a key role in preventing or contributing to the development of chronic diseases, such as obesity, allergy, and brain disorders. Supplementation of maternal diet with prebiotics has been shown to reduce the risk of food allergies and affect the intestinal permeability in offspring later in life. However, its role in modulating the development of other intestinal disorders, such as colitis, remains unknown. Therefore, we investigated the effects of prebiotic supplementation in pregnant mice on the occurrence of colitis in their offspring., Materials and Methods: Offspring from mothers, who were administered prebiotic galacto-oligosaccharides and inulin during gestation or fed a control diet, were subjected to three cycles of dextran sulphate sodium (DSS) treatment to induce chronic colitis, and their intestinal function and disease activity were evaluated. Colonic remodelling, gut microbiota composition, and lipidomic and transcriptomic profiles were also assessed., Results: DSS-treated offspring from prebiotic-fed mothers presented a higher disease score, increased weight loss, and increased faecal humidity than those from standard diet-fed mothers. DSS-treated offspring from prebiotic-fed mothers also showed increased number of colonic mucosal lymphocytes and macrophages than the control group, associated with the increased colonic concentrations of resolvin D5, protectin DX, and 14-hydroxydocosahexaenoic acid, and modulation of colonic gene expression. In addition, maternal prebiotic supplementation induced an overabundance of eight bacterial families and a decrease in the butyrate caecal concentration in DSS-treated offspring., Conclusion: Maternal prebiotic exposure modified the microbiota composition and function, lipid content, and transcriptome of the colon of the offspring. These modifications did not protect against colitis, but rather sensitised the mice to colitis development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lê, Selle, Aubert, Durand, Brosseau, Bordron, Delage, Chaffron, Petitfils, Cenac, Neunlist, Bodinier and Rolli-Derkinderen.)

Published
2023
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49. Inflammatory bowel disease therapeutic strategies by modulation of the microbiota: how and when to introduce pre-, pro-, syn-, or postbiotics?

Author

Lê A, Mantel M, Marchix J, Bodinier M, Jan G, and Rolli-Derkinderen M

Subjects
Humans, Dysbiosis therapy, Inflammation, Inflammatory Bowel Diseases, Microbiota, Colitis, Ulcerative pathology
Abstract

Inflammatory bowel diseases (IBD), a heterogeneous group of inflammatory conditions that encompass both ulcerative colitis and Crohn's disease, represent a major public health concern. The etiology of IBD is not yet fully understood and no cure is available, with current treatments only showing long-term effectiveness in a minority of patients. A need to increase our knowledge on IBD pathophysiology is growing, to define preventive measures, to improve disease outcome, and to develop new effective and lasting treatments. IBD pathogenesis is sustained by aberrant immune responses, associated with alterations of the intestinal epithelial barrier (IEB), modifications of the enteric nervous system, and changes in microbiota composition. Currently, most of the treatments target the inflammation and the immune system, but holistic approaches targeting lifestyle and diet improvements are emerging. As dysbiosis is involved in IBD pathogenesis, pre-, pro-, syn-, and postbiotics are used/tested to reduce the inflammation or strengthen the IEB. The present review will resume these works, pointing out the stage of life, the duration, and the environmental conditions that should go along with microbiota or microbiota-derived treatments.

Published
2022
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50. A 9-mRNA signature measured from whole blood by a prototype PCR panel predicts 28-day mortality upon admission of critically ill COVID-19 patients.

Author

Tardiveau C, Monneret G, Lukaszewicz AC, Cheynet V, Cerrato E, Imhoff K, Peronnet E, Bodinier M, Kreitmann L, Blein S, Llitjos JF, Conti F, Gossez M, Buisson M, Yonis H, Cour M, Argaud L, Delignette MC, Wallet F, Dailler F, Monard C, Brengel-Pesce K, and Venet F

Subjects
Humans, RNA, Messenger, Hospitalization, Polymerase Chain Reaction, Critical Illness, COVID-19
Abstract

Immune responses affiliated with COVID-19 severity have been characterized and associated with deleterious outcomes. These approaches were mainly based on research tools not usable in routine clinical practice at the bedside. We observed that a multiplex transcriptomic panel prototype termed Immune Profiling Panel (IPP) could capture the dysregulation of immune responses of ICU COVID-19 patients at admission. Nine transcripts were associated with mortality in univariate analysis and this 9-mRNA signature remained significantly associated with mortality in a multivariate analysis that included age, SOFA and Charlson scores. Using a machine learning model with these 9 mRNA, we could predict the 28-day survival status with an Area Under the Receiver Operating Curve (AUROC) of 0.764. Interestingly, adding patients' age to the model resulted in increased performance to predict the 28-day mortality (AUROC reaching 0.839). This prototype IPP demonstrated that such a tool, upon clinical/analytical validation and clearance by regulatory agencies could be used in clinical routine settings to quickly identify patients with higher risk of death requiring thus early aggressive intensive care., Competing Interests: CT, VC, EC, KI, KB-P, EP, MBo, LK, SB, and J-FL are bioMérieux’s employees. EP, GM, and FV are co-inventors in patent applications covering the following markers: CX3CR1, CD127, IL10 and S100A9. bioFire – a bioMérieux company - holds patents on the technology. This does not alter the authors’ adherence to all the policies on sharing data and materials. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tardiveau, Monneret, Lukaszewicz, Cheynet, Cerrato, Imhoff, Peronnet, Bodinier, Kreitmann, Blein, Llitjos, Conti, Gossez, Buisson, Yonis, Cour, Argaud, Delignette, Wallet, Dailler, Monard, Brengel-Pesce, Venet and the RICO study group.)

Published
2022
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