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51. Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

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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

52. Heterogeneity of HLA Class II Gene Products as Studied in a Family by Sequential Immunoprecipitation

Author

Bontrop, R. E., Koning, F., v. Miltenburg, R., Gerrets, R., Thompson, A., Schuurman, R., Giphart, M. J., Albert, Ekkehard D., editor, Baur, Max P., editor, Mayr, Wolfgang R., editor, Bertrams, J., editor, Goldmann, S., editor, Grosse-Wilde, H., editor, Opelz, G., editor, Rittner, C., editor, Schendel, D. J., editor, Scholz, S., editor, and Wank, R., editor

Published
1984
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56. An Arthritis-Suppressive and Treg Cell-Inducing CD4+T Cell Epitope Is Functional in the Context of HLA-Restricted T Cell Responses

Author

Wolf, C. de, Zee, R. van der, Braber, I. den, Glant, T., Maillere, B., Favry, E., Lummel, M. van, Koning, F., Hoek, A., Ludwig, I., Eden, W. van, Broere, F., and LS Immunologie

Abstract

Previously, we have shown that mycobacterial heat shock protein 70 (HSP70)-derived peptide B29 induces B29-specific regulatory T cells, which suppressed experimental arthritis in mice by cross-recognition of their mammalian HSP70 homologs (1). The aim of this study is to characterize the B29 binding and specific CD4(+) T cell responses in the context of human MHC molecules (HLA). Binding of B29 peptide and its mammalian homologs to HLA molecules was examined with competitive binding assays. The effect of B29 immunization was assessed in proteoglycan-induced arthritis in HLA-DQ8 transgenic mice, followed by ex vivo restimulation with B29 to examine the T cell response. Human PBMC were used to investigate the presence of B29-specific T cells with immunoregulatory potential. We found a high to moderate binding affinity for multiple HLA-DR and HLA-DQ molecules, including those highly associated with rheumatoid arthritis. This binding was functional, as B29 immunization resulted in suppression of arthritis and T cell responses in HLA-DQ8 transgenic mice. In humans, we demonstrated the presence and expansion of B29-specific CD4(+) T cells, which were cross-reactive with the mammalian homologs. With HLA-DR4(+) tetramers specific for B29 or mB29b we showed expansion of cross-reactive T cells, especially the human CD4(+) CD25(+) FoxP3(+) T cell population after in vitro stimulation with B29. These results demonstrated a conserved fine-specificity and functionality of the B29-induced regulatory T cell responses in the context of the human MHC. Based on these findings, a translational path of the B29 experimental findings into a clinical immunomodulatory therapeutic approach comes within reach. This article is protected by copyright. All rights reserved.

Published
2016

58. Celiac disease: quantity matters

Author

Koning, F.

Subjects
Glutens, Tissue transglutaminase, T-Lymphocytes, T cell, Immunology, Review, Cross Reactions, Models, Biological, digestive system, Immune system, Glutenin, HLA-DQ Antigens, medicine, Humans, Immunology and Allergy, Triticum, chemistry.chemical_classification, biology, Age Factors, food and beverages, nutritional and metabolic diseases, Glutamic acid, Gluten, digestive system diseases, Glutamine, Celiac Disease, medicine.anatomical_structure, chemistry, Biochemistry, biology.protein, Peptides, Gliadin
Abstract

Celiac disease (CD) is caused by uncontrolled immune responses to the gluten proteins in wheat and related cereals. Gluten is a complex mixture of gliadin and glutenin proteins and most modern wheat varieties contain up to 100 highly related, but distinct gluten proteins. Invariably, these gliadin and glutenin proteins contain immunogenic peptides, particularly so after the peptides have been modified by the enzyme tissue transglutaminase (TG2). This modification results in the conversion of glutamine residues in the gluten peptides into the negatively charged glutamic acid. This generates peptides that bind strongly to the disease predisposing HLA-DQ2.5 or -DQ8 molecules and this facilitates the induction of disease-inducing CD4 T cell responses, a hallmark of CD. It is well-known that the HLA-DQ genotype determines the risk of disease development. Moreover, the abundance of immunogenic peptides in the gluten proteins is likely linked to the observation that polyclonal T cell responses to multiple gluten peptides are usually found in patients with CD. However, not all patients respond to the same set of peptides. Here, I propose a model that integrates these observations and links them to the highly variable clinical spectrum of symptoms that are associated with CD. Moreover, I discuss whether it is feasible to alter wheat and/or gluten to make it suitable for consumption by CD patients.

Published
2012

60. IgG is elevated in obese white adipose tissue but does not induce glucose intolerance via Fcγ-receptor or complement

Author

van Dam, A D, primary, van Beek, L, additional, Pronk, A C M, additional, van den Berg, S M, additional, Van den Bossche, J, additional, de Winther, M P J, additional, Koning, F, additional, van Kooten, C, additional, Rensen, P C N, additional, Boon, M R, additional, Verbeek, J S, additional, van Dijk, K Willems, additional, and van Harmelen, V, additional

Published
2017
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61. Macrophage-mediated gliadin degradation and concomitant IL-27 production drive IL-10- and IFN-γ-secreting Tr1-like-cell differentiation in a murine model for gluten tolerance

Author

van Leeuwen, M.A., primary, Costes, L M M, additional, van Berkel, L.A., additional, Simons-Oosterhuis, Y., additional, du Pré, M.F., additional, Kozijn, A.E., additional, Raatgeep, H.C., additional, Lindenbergh-Kortleve, D.J., additional, van Rooijen, N., additional, Koning, F., additional, and Samsom, J.N., additional

Published
2017
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62. Recent insight in the pathophysiology of coeliac disease: relevance to rheumatoid arthritis

Author

Koning, F.

Subjects
CD4-Positive T-Lymphocytes, B cells, Glutens, T cells, Receptors, Antigen, T-Cell, Autoimmunity, HLA, Arthritis, Rheumatoid, Celiac Disease, HLA-DQ Antigens, Immune Tolerance, Animals, Humans, T cell receptor, Protein Binding, Signal Transduction
Abstract

Coeliac disease (CD) is a T cell mediated inflammatory disorder of the small intestine that affects approximately 1% of the population (1, 2). CD is triggered by gluten ingestion, proteins found in wheat, barley and rye. CD4(+) T cells specific for post-translationally modified gluten peptides bound to the disease-predisposing HLA-DQ2 or HLADQ8 molecules are typically found in patients with CD, explaining the strong association between these HLA-alleles and the occurrence of CD (1, 2). In addition, antibodies specific for modified gluten are also present in patients with CD, implying a role for B to T cell presentation (1). Recent studies have determined the T cell repertoire (TCR) that is utilised by gluten-specific T cells in HLA-DQ2(+) and HLA-DQ8(+) patients and structures between such TCR and HLA-DQ-gluten peptide complexes have been solved (3-7). In HLA-DQ2 patients the TCR repertoire specific for an immunodominant gluten peptide is dominated by the expression of TRAV26 and TRBV7-2 (3-5) while in HLA-DQ8(+) patients such T cells frequently express TRAV26 and TRBV9 (6, 7). Moreover, in the TCR-HLADQ-gluten complexes a non-germline encoded arginine is positioned in the interface between the TCR and HLADQ-gluten which makes critical interactions with both HLA-DQ and the bound peptide (5-7). Collectively, these observations point to stringent selection of a high affinity TCR repertoire in patients with CD. Similar mechanisms are likely to play a role in rheumatoid arthritis (RA).

Published
2015

65. Crossreactivity to vinculin and microbes provides a molecular basis for HLA-based protection against rheumatoid arthritis

Author

Van Heemst, J., Jansen, D. T. S. L., Polydorides, Savvas, Moustakas, Antonis K., Bax, M., Feitsma, A. L., Bontrop-Elferink, D. G., Baarse, M., Van Der Woude, D., Wolbink, G. -J, Rispens, T., Koning, F., De Vries, R. R. P., Papadopoulos, George K., Archontis, Georgios Z., Huizinga, T. W., Toes, R. E., Landsteiner Laboratory, and Archontis, Georgios Z. [0000-0002-7750-8641]

Subjects
rheumatoid arthritis, microorganism, Models, Molecular, Enzyme-Linked Immunospot Assay, HLA DRB1 antigen, peripheral blood mononuclear cell, enzyme linked immunospot assay, T-Lymphocytes, General Physics and Astronomy, Arthritis, HLA DR antigen, Autoantigens, Epitope, Western blotting, immunology, Arthritis, Rheumatoid, Epitopes, immune system diseases, HLA Antigens, antibody, T lymphocyte, HLA SE antigen, molecular mimicry, HLA DQ8 antigen, cross reaction, skin and connective tissue diseases, Peptide sequence, donor, epitope, Antigen Presentation, Multidisciplinary, biology, HLA DQB1 antigen, Vinculin, bacterium, molecular mechanics, autoantigen, Tissue Donors, unclassified drug, antigen recognition, Blot, risk factor, Rheumatoid arthritis, Viruses, HLA DQ antigen, gamma interferon, HLA system, musculoskeletal diseases, HLA antigen, HLA DQ5 antigen, Blotting, Western, Molecular Sequence Data, virus, Human leukocyte antigen, Cross Reactions, chemistry, microbial activity, Article, General Biochemistry, Genetics and Molecular Biology, HLA DQA1 antigen, Interferon-gamma, antigen, HLA-DQ Antigens, medicine, Humans, molecular analysis, human, Amino Acid Sequence, Allele, HLA DQ7 antigen, CD4+ T lymphocyte, nonhuman, Bacteria, vinculin, human cell, disease predisposition, Models, Immunological, General Chemistry, biological model, medicine.disease, molecular dynamics, amino acid sequence, antigen presentation, disability, antigen presenting cell, molecular genetics, citrulline, Immunology, chemical structure, biology.protein, Citrulline, protein, metabolism, pathogen, HLA-DRB1 Chains
Abstract

The HLA locus is the strongest risk factor for anti-citrullinated protein antibody (ACPA) + rheumatoid arthritis (RA). Despite considerable efforts in the last 35 years, this association is poorly understood. Here we identify (citrullinated) vinculin, present in the joints of ACPA + RA patients, as an autoantigen targeted by ACPA and CD4 + T cells. These T cells recognize an epitope with the core sequence DERAA, which is also found in many microbes and in protective HLA-DRB1∗13 molecules, presented by predisposing HLA-DQ molecules. Moreover, these T cells crossreact with vinculin-derived and microbial-derived DERAA epitopes. Intriguingly, DERAA-directed T cells are not detected in HLA-DRB1∗13 + donors, indicating that the DERAA epitope from HLA-DRB1∗13 mediates (thymic) tolerance in these donors and explaining the protective effects associated with HLA-DRB1∗13. Together our data indicate the involvement of pathogen-induced DERAA-directed T cells in the HLA-RA association and provide a molecular basis for the contribution of protective/predisposing HLA alleles. 6 Cited By :21

Published
2015

66. Triticinae alpha-gliadin storage protein gene, partial cds

Author

van Herpen, T.W.J.M., Goryunova-Svetlana, V., van der Schoot, J., Mitreva, M., Salentijn, E.M.J., Vorst, O.F.J., Schenk, M.F., van Veelen, P., de Koning, F., van Soest, L.J.M., Vosman, B.J., Bosch, H.J., Gilissen, L.J.W.J., Smulders, M.J.M., van Herpen, T.W.J.M., Goryunova-Svetlana, V., van der Schoot, J., Mitreva, M., Salentijn, E.M.J., Vorst, O.F.J., Schenk, M.F., van Veelen, P., de Koning, F., van Soest, L.J.M., Vosman, B.J., Bosch, H.J., Gilissen, L.J.W.J., and Smulders, M.J.M.

Published
2016

67. Review article: future research on coeliac disease - a position report from the European multistakeholder platform on coeliac disease (CDEUSSA)

Author

Troncone R, Ivarsson A, Szajewska H, Mearin ML, Members of European Multistakeholder Platform on CD, Bai J, Deutsch H, Scerri C, van Winckel M, Wanty C, Kolacek S, Misak Z, Hadjiminas J, Stepánková R, Tlaskalová Hogenová H, Tucková L, Madsen C, Maki M, Kaukinen K, Lahdeaho MJ, Cerf Bensussan N, Jarry B, Cellier C, Bullinger M, Stern M, Ruland A, Mummert E, Wieser H, Laass M, Severin D, Eleftheria R, Papadopoulou A, Korponay I, Berant M, Branski D, Shamir R, Accomando S, Bravi E, Gianfrani C, Gobetti M, Greco L, Lionetti P, Mazzarella P, Oderda G, Pitschieller K, Rossi M, Bonamico M, Eglite L, Kaze I, Marcis L, Hogen Esch CE, Hopman E, van Koppen E, Koning F, Schweizer JJ, Vermeulen B, Brand H, Mulder CJ, Kneepkens CM, Buitendijk S, Pereira R, Gilissen L, Bindels J, Wolters V, Wijmenga C, Hadithi M, Mourad PE, Janssen FW, Verhage J, Sollid L, Lundin K, Duta D, Stanescu A, Plesa A, Dolinsek J, Micetic Turk D, Espin Jaime B, Garcia Alonso L, Juste Ruiz M, Castillejo G, Manzanares J, Canabate Reche F, Polanco I, Ribes Koninckx C, Roman E, Urruzuno P, Varea V, O'Sullivan C, Garotte J, Arranz E, Cilleruelo L, Hammerström ML, Holmberg D, Lindholm L, Rosen A, Myleus A, Norstrom F, Carlsson A, Nordyke K, Jansson A, Ertem D, Mowat A, Ahmed M, Ciclitira P, Ellis J, Mills EN, Spray C, West J, Watson P, Fasano A, Pietzak M., TOLONE, Carlo, Troncone, R, Ivarsson, A, Szajewska, H, Mearin, Ml, Members of European Multistakeholder Platform on, Cd, Bai, J, Deutsch, H, Scerri, C, van Winckel, M, Wanty, C, Kolacek, S, Misak, Z, Hadjiminas, J, Stepánková, R, Tlaskalová Hogenová, H, Tucková, L, Madsen, C, Maki, M, Kaukinen, K, Lahdeaho, Mj, Cerf Bensussan, N, Jarry, B, Cellier, C, Bullinger, M, Stern, M, Ruland, A, Mummert, E, Wieser, H, Laass, M, Severin, D, Eleftheria, R, Papadopoulou, A, Korponay, I, Berant, M, Branski, D, Shamir, R, Accomando, S, Bravi, E, Gianfrani, C, Gobetti, M, Greco, L, Lionetti, P, Mazzarella, P, Oderda, G, Pitschieller, K, Tolone, Carlo, Rossi, M, Bonamico, M, Eglite, L, Kaze, I, Marcis, L, Hogen Esch, Ce, Hopman, E, van Koppen, E, Koning, F, Schweizer, Jj, Vermeulen, B, Brand, H, Mulder, Cj, Kneepkens, Cm, Buitendijk, S, Pereira, R, Gilissen, L, Bindels, J, Wolters, V, Wijmenga, C, Hadithi, M, Mourad, Pe, Janssen, Fw, Verhage, J, Sollid, L, Lundin, K, Duta, D, Stanescu, A, Plesa, A, Dolinsek, J, Micetic Turk, D, Espin Jaime, B, Garcia Alonso, L, Juste Ruiz, M, Castillejo, G, Manzanares, J, Canabate Reche, F, Polanco, I, Ribes Koninckx, C, Roman, E, Urruzuno, P, Varea, V, O'Sullivan, C, Garotte, J, Arranz, E, Cilleruelo, L, Hammerström, Ml, Holmberg, D, Lindholm, L, Rosen, A, Myleus, A, Norstrom, F, Carlsson, A, Nordyke, K, Jansson, A, Ertem, D, Mowat, A, Ahmed, M, Ciclitira, P, Ellis, J, Mills, En, Spray, C, West, J, Watson, P, Fasano, A, and Pietzak, M.

Abstract

BACKGROUND: CDEUSSA is a Specific Support Action project from the Sixth Framework Programme Priority of the European Union (EU). Its aim is to bring together basic and applied research in the area of coeliac disease (CD). This paper reviews the main issues that are a result of the CDEUSSA initiative. AIM: To identify the major issues in need of investigation in the areas of clinical aspects, treatment, prevention and public health. METHODS: Key stakeholders, representing a wide range of knowledge with crucial importance for CD research and practice, have participated in two workshops aimed at identifying and proposing to the EU, as high priority research, topics in the areas of clinical aspects, treatment, prevention and public health. RESULTS: In public health, the overall goal should be to improve quality of life of the European population by implementing primary prevention strategies, early diagnosis and improved treatments for CD. New treatment strategies need to be developed. The option of primary prevention should be fully explored, which requires combined epidemiological, clinical and basic scientific research efforts. Such studies should also consider the importance of gene-environment interactions in the development of CD. Increased knowledge is needed on the natural history of CD. Diagnostic criteria need to be revised. CONCLUSIONS: To achieve these goals, a collaboration of the stakeholders is fundamental, including research and patient organizations, as well as industries within both diagnostics and food production.

Published
2008

70. AN IMMUNODOMINANT DQ8-RESTRICTED GLIADIN PEPTIDE ACTIVATES SMALL INTESTINAL IMMUNE RESPONSE IN 'IN VITRO' CULTURED MUCOSA FROM HLA-DQ8, BUT NOT HLA-DQ2 POSITIVE COELIAC PATIENTS

Author

MAZZARELLA G., MAGLIO M., PAPARO F., STEFANILE R., GRECO, LUIGI, VAN DE WAL Y., KOOY Y., KONING F., AURICCHIO S., NARDONE, GERARDO ANTONIO PIO, TRONCONE, RICCARDO, Mazzarella, G., Maglio, M., Paparo, F., Nardone, GERARDO ANTONIO PIO, Stefanile, R., Greco, Luigi, VAN DE WAL, Y., Kooy, Y., Koning, F., Auricchio, S., and Troncone, Riccardo

Published
2003

77. Immune response to 100 mg gluten introduced at 4 months of age: results from the PreventCD cohort

Author

Korponay-Szabo, I, Gyimesi, J, Koletzko, S, Castillejo, G, Hogen Esch, CE, Mummert, E, Troncone, R, Szajewska, H, Polanco, I, Ribes, C, Shamir, R, Kolaček, Sanja, Koning, F, and Mearin, ML.

Subjects
nutritional and metabolic diseases, biochemical phenomena, metabolism, and nutrition, digestive system diseases, celiac disease
Abstract

Immune response to 100 mg gluten introduced at 4 months of age: results from the PreventCD cohort.

Published
2011

78. Immune response to 100 mg gluten introduced at 4 months of age: results from the PreventCD cohort

Author

2. Korponay-Szabo I, Gyimesi J, Koletzko S, Castillejo G, Hogen Esch CE, Mummert E, Troncone R, Szajewska H, Polanco I, Ribes C, Shamir R, Kolaček, Sanja, and Koning F, Mearin ML.

Subjects
nutritional and metabolic diseases, biochemical phenomena, metabolism, and nutrition, digestive system diseases, coeliac disease
Abstract

Immune response to 100 mg gluten introduced at 4 months of age: results from the PreventCD cohort.

Published
2011

79. Gluten toxicity, how to get rid of it?

Author

Koning, F. and Smulders, M.J.M.

Subjects
Plant Breeding, Life Science, food and beverages, nutritional and metabolic diseases, digestive system diseases
Published
2011

81. The PreventCD Study design: towards new strategies for the prevention of coeliac disease

Author

Esch, C.E.H., Rosen, A., Auricchio, R., Romanos, J., Chmielewska, A., Putter, H., Ivarsson, A., Szajewska, H., Koning, F., Wijmenga, C., Troncone, R., Mearin, M.L., and PreventCD Study Grp

Subjects
breast-feeding coeliac disease infant nutrition primary prevention risk factors quality-of-life gluten introduction risk variants genetic risk children epidemic hla histopathology questionnaire association
Abstract

Background PreventCD (www.preventcd.com) is a European multicentre study, which studies the influence of infant nutrition, and that of genetic, immunologic and environmental factors, on the risk of developing coeliac disease (CD). The hypothesis is that it is possible to induce tolerance to gluten by introducing small quantities of gluten to infants, preferably while they are still being breast-fed, and that this might also reduce the risk for related autoimmune disorders. Aim To describe the design of this ongoing European CD research project. Methods PreventCD encompasses two study designs and two study populations: (i) a European multicentre study: a prospective, double-blind, randomized dietary-intervention study among infants from families with high risk of CD, and (ii) a Swedish population-based CD screening study among 12-year-olds from the general population, divided into two birth cohorts that differ with respect to infant feeding practices. Discussion PreventCD is expected to elucidate some of the genetic and immunological mechanisms involved in the process of immune intolerance. Eur J Gastroenterol Hepatol 22:1424-1430 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Published
2010

82. A Universal Approach to Eliminate Antigenic Properties of Alpha-Gliadin Peptides in Celiac Disease

Author

Mitea, C., Salentijn, E.M.J., Veelen, P. van, Goryunova, S.V., Meer, I.M. van der, Broeck, H.C. van den, Mujico, J.R., Monserrat, V., Gilissen, L.J.W.J., Drijfhout, J.W., Dekking, L., Koning, F., and Smulders, M.J.M.

Subjects
food and beverages, nutritional and metabolic diseases, t-cell response tissue transglutaminase cereal toxicity wheat epitopes arabidopsis mutagenesis prevalence varieties explains, digestive system, digestive system diseases
Abstract

Celiac disease is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins, including the alpha-gliadins. It has been shown that alpha-gliadins harbor several major epitopes involved in the disease pathogenesis. A major step towards elimination of gluten toxicity for celiac disease patients would thus be the elimination of such epitopes from alpha-gliadins. We have analyzed over 3,000 expressed alpha-gliadin sequences from 11 bread wheat cultivars to determine whether they encode for peptides potentially involved in celiac disease. All identified epitope variants were synthesized as peptides and tested for binding to the disease-associated HLA-DQ2 and HLA-DQ8 molecules and for recognition by patient-derived alpha-gliadin specific T cell clones. Several specific naturally occurring amino acid substitutions were identified for each of the alpha-gliadin derived peptides involved in celiac disease that eliminate the antigenic properties of the epitope variants. Finally, we provide proof of principle at the peptide level that through the systematic introduction of such naturally occurring variations alpha-gliadins genes can be generated that no longer encode antigenic peptides. This forms a crucial step in the development of strategies to modify gluten genes in wheat so that it becomes safe for celiac disease patients. It also provides the information to design and introduce safe gluten genes in other cereals, which would exhibit improved quality while remaining safe for consumption by celiac disease patients.

Published
2010

83. The tortoise and the hare: slowly evolving T-cell responses take hastily evolving KIR

Author

Bergen, J. van and Koning, F.

Subjects
CMV MHC HLA natural Killer cell Receptors KIR rheumatology T cells ig-like receptor immunoglobulin-like receptors natural-killer-cells mhc class-i human cytomegalovirus-infection inhibitory receptors rheumatoid-arthritis nk cells hla-c lymphokine production, chemical and pharmacologic phenomena
Abstract

P>The killer cell immunoglobulin-like receptor (KIR) locus comprises a variable and rapidly evolving set of genes encoding multiple inhibitory and activating receptors. The activating receptors recently evolved from the inhibitory receptors and both bind HLA class I and probably also class I-like structures induced by viral infection. Although generally considered natural killer (NK) cell receptors, KIR are also expressed by a large fraction of effector memory T cells, which slowly accumulate during human life. These effector memory cells are functionally similar to NK cells, as they are immediate effector cells that are cytotoxic and produce IFN-gamma. However, different rules apply to NK and T cells with respect to KIR expression and function. For example, KIR tend to modulate signals driven by the T-cell receptor (TCR) rather than to act independently, and use different signal transduction pathways to modulate only a subset of effector functions. The most important difference may lie in the rules governing tolerance: while NK cells with activating KIR binding self-HLA are hyporesponsive, the same is unlikely to apply to T cells. We argue that the expression of activating KIR on virus-specific T cells carrying TCR that weakly cross-react with autoantigens can unleash the autoreactive potential of these cells. This may be the case in rheumatoid arthritis, where cytomegalovirus-specific KIR2DS2+ T cells might cause vasculitis. Thus, the rapid evolution of activating KIR may have allowed for efficient NK-cell control of viruses, but may also have increased the risk that slowly evolving T-cell responses to persistent pathogens derail into autoimmunity.

Published
2010

84. AIDS-protective HLA-B*27/B*57 and chimpanzee MHC class I molecules target analogous conserved areas of HIV-1/SIVcpz

Author

Groot, N.G. de, Heijmans, C.M.C., Zoet, Y.M., Ru, A.H. de, Verreck, F.A., Veelen, P.A. van, Drijfhout, J.W., Doxiadis, G.G.M., Remarque, E.J., Doxiadis, I.I.N., Rood, J.J. van, Koning, F., and Bontrop, R.E.

Subjects
HIV/SIV peptide-binding selection selective sweep immunodeficiency-virus type-1 peptide-binding-specificity hiv-1 infection wild chimpanzees selective sweep gene repertoire receptor gene hla-b sivcpz association
Abstract

In the absence of treatment, most HIV-1-infected humans develop AIDS. However, a minority are long-term nonprogressors, and resistance is associated with the presence of particular HLA-B*27/B*57 molecules. In contrast, most HIV-1-infected chimpanzees do not contract AIDS. In comparison with humans, chimpanzees experienced an ancient selective sweep affecting the MHC class I repertoire. We have determined the peptide-binding properties of frequent chimpanzee MHC class I molecules, and show that, like HLA-B*27/B*57, they target similar conserved areas of HIV1/SIVcpz. In addition, many animals appear to possess multiple molecules targeting various conserved areas of the HIV-1/SIVcpz Gag protein, a quantitative aspect of the immune response that may further minimize the chance of viral escape. The functional characteristics of the contemporary chimpanzee MHC repertoire suggest that the selective sweep was caused by a lentiviral pandemic.

Published
2010

86. S13 complex

Author

Petersen, J., primary, Rossjohn, J., additional, Reid, H.H., additional, and Koning, F., additional

Published
2015
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87. L3-12 complex

Author

Petersen, J., primary, Rossjohn, J., additional, Reid, H.H., additional, and Koning, F., additional

Published
2015
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88. T316 complex

Author

Petersen, J., primary, Rossjohn, J., additional, Reid, H.H., additional, and Koning, F., additional

Published
2015
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90. Randomized feeding intervention in infants at high risk for celiac disease

Author

Vriezinga, S. L., Auricchio, R., Bravi, E., Castillejo, G., Chmielewska, A., Crespo Escobar, P., Kolaček, S., Koletzko, S., Korponay-Szabo, I. R., Mummert, E., Polanco, I., Putter, H., Ribes-Koninckx, C., Shamir, R., Szajewska, H., Werkstetter, K., Greco, L., Gyimesi, J., Hartman, C., Esch, C. Hogen, Hopman, E., Ivarsson, Anneli, Koltai, T., Koning, F., Martinez-Ojinaga, E., te Marvelde, C., Pavic, A. Mocic, Romanos, J., Stoopman, E., Villanacci, V., Wijmenga, C., Troncone, R., Mearin, M. L., Vriezinga, S. L., Auricchio, R., Bravi, E., Castillejo, G., Chmielewska, A., Crespo Escobar, P., Kolaček, S., Koletzko, S., Korponay-Szabo, I. R., Mummert, E., Polanco, I., Putter, H., Ribes-Koninckx, C., Shamir, R., Szajewska, H., Werkstetter, K., Greco, L., Gyimesi, J., Hartman, C., Esch, C. Hogen, Hopman, E., Ivarsson, Anneli, Koltai, T., Koning, F., Martinez-Ojinaga, E., te Marvelde, C., Pavic, A. Mocic, Romanos, J., Stoopman, E., Villanacci, V., Wijmenga, C., Troncone, R., and Mearin, M. L.

Abstract

BACKGROUND A window of opportunity has been suggested for reducing the risk of celiac disease by introducing gluten to infants at 4 to 6 months of age. METHODS We performed a multicenter, randomized, double-blind, placebo-controlled dietary-intervention study involving 944 children who were positive for HLA-DQ2 or HLA-DQ8 and had at least one first-degree relative with celiac disease. From 16 to 24 weeks of age, 475 participants received 100 mg of immunologically active gluten daily, and 469 received placebo. Anti-transglutaminase type 2 and antigliadin antibodies were periodically measured. The primary outcome was the frequency of biopsy-confirmed celiac disease at 3 years of age. RESULTS Celiac disease was confirmed by means of biopsies in 77 children. To avoid underestimation of the frequency of celiac disease, 3 additional children who received a diagnosis of celiac disease according to the 2012 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria (without having undergone biopsies) were included in the analyses (80 children; median age, 2.8 years; 59% were girls). The cumulative incidence of celiac disease among patients 3 years of age was 5.2% (95% confidence interval [CI], 3.6 to 6.8), with similar rates in the gluten group and the placebo group (5.9% [95% CI, 3.7 to 8.1] and 4.5% [95% CI, 2.5 to 6.5], respectively; hazard ratio in the gluten group, 1.23; 95% CI, 0.79 to 1.91). Rates of elevated levels of anti-transglutaminase type 2 and antigliadin antibodies were also similar in the two study groups (7.0% [95% CI, 4.7 to 9.4] in the gluten group and 5.7% [95% CI, 3.5 to 7.9] in the placebo group; hazard ratio, 1.14; 95% CI, 0.76 to 1.73). Breast-feeding, regardless of whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence the development of celiac disease or the effect of the intervention. CONCLUSIONS As compared with placebo, the introduction of small quantiti

Published
2014
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91. Dominance of an alternative CLIP sequence in the celiac disease associated HLA-DQ2 molecule

Author

Wiesner, M., Stepniak, D., de Ru, A. H., Moustakis, A. K., Drijfhout, J. W., Papadopoulos, G. K., van Veelen, P. A., and Koning, F.

Subjects
Models, Molecular, Histocompatibility Antigens Class II/immunology/metabolism, Peptides/immunology/metabolism, Antigens, Differentiation, B-Lymphocyte/immunology/metabolism, Protein Conformation, Molecular Sequence Data, Celiac Disease/*immunology, Humans, Amino Acid Sequence, Mass Spectrometry, HLA-DQ Antigens/chemistry/genetics/*immunology, Protein Binding
Abstract

During assembly, HLA class II molecules associate with the invariant chain. As the result, the peptide-binding groove is occupied by an invariant chain peptide termed CLIP (class-II-associated invariant chain peptide; sequence MRMATPLLM). By mass spectrometry, we have now characterized peptides that are naturally present in HLA-DQ2. This analysis revealed that 22 variants of Ii-derived peptides are associated with HLA-DQ2. Strikingly, the large majority of those do not contain the conventional CLIP sequence MRMATPLLM, but instead a peptide that partially overlaps with CLIP, sequence TPLLMQALPM. Peptide binding studies indicate that this alternative CLIP peptide has superior HLA-DQ2 binding properties compared to the conventional CLIP and that the minimal nine-amino-acid binding core consists of the sequence PLLMQALPM, findings that could be corroborated by molecular simulation. The alternative CLIP peptide was also found to be present in HLA-DQ2 molecules isolated from human thymus. Moreover, the alternative CLIP peptide was also found in association with HLA-DQ8. Together, these results indicate that HLA-DQ2 and HLA-DQ8 associate with an alternative CLIP sequence, a property that may relate to the strong association between HLA-DQ molecules and human autoimmune diseases. Immunogenetics

Published
2008

92. Immunization with mannosylated peptide induces poor T cell effector functions despite enhanced antigen presentation

Author

Kel, J.M., Geus, E.D. de, Stipdonk, M.J. van, Drijfhout, J.W., Koning, F., Nagelkerken, L., Risk Assessment of Toxic and Immunomodulatory Agents, Strategic Infection Biology, Dep Infectieziekten Immunologie, and TNO Kwaliteit van Leven

Subjects
Immune modulation, animal cell, delayed hypersensitivity, Lymphocyte Activation, Th1 immunity, Mice, T lymphocyte, C-type lectins, Hypersensitivity, Delayed, cell fate, Antigen Presentation, Delayed-type hypersensitivity, Th1 cell, article, ovalbumin, lymph node, female, priority journal, cytokine production, effector cell, gamma interferon, CD4 antigen, in vitro study, animal experiment, Molecular Sequence Data, Receptors, Antigen, T-Cell, Mice, Transgenic, cellular immunity, macrophage, lymphocyte proliferation, immunization, animal tissue, in vivo study, lymphocytic infiltration, immunoglobulin G2a, Animals, controlled study, immunoglobulin blood level, Amino Acid Sequence, mouse, lymphoblast, CD4+ T lymphocyte, L selectin, nonhuman, antiinflammatory activity, Th1 Cells, Mice, Inbred C57BL, clonal variation, antigen specificity, antigen expression, molecular recognition, T lymphocyte receptor, Peptides, Mannose, spleen cell
Abstract

In this study, we investigated the development of T cell responses in mice after administration of a mannosylated ovalbumin peptide (M-OVA323-339). Immunization with M-OVA323-339 in complete adjuvant resulted in enhanced antigen presentation in draining lymph nodes. Monitoring the fate of CFSE-labeled ovalbumin peptide-specific TCR transgenic CD4+ T cells revealed that immunization with M-OVA323-339 induced normal clonal expansion, recirculation and CD62L expression of antigen-specific T cells in vivo. However, these T cells developed only poor effector functions, reflected by minimal IFN-γ production, low IgG2a levels in serum and poor peptide-specific delayed-type hypersensitivity (DTH) responses. This diminished inflammatory response was associated with decreased infiltration of T cell blasts and macrophages. Importantly, also mice with functional effector T cells did not mount a robust DTH response after a challenge with M-OVA323-339 in the ear, although their T cells responded normally to M-OVA323-339 in vitro. In conclusion, mannosylated peptide induces proliferation of T cells with impaired Th1 cell effector functions and additionally abrogates the activity of pre-existing effector T cells. © The Japanese Society for Immunology. 2007. All rights reserved.

Published
2008

96. Mannosylated PLP139-151 induces peptide-specific tolerance to experimental autoimmune encephalomyelitis

Author

Luca, M.E., Kel, J.M., Rijs, W. van, Drijfhout, J.W., Koning, F., Nagelkerken, L., and Gaubius Instituut TNO

Subjects
Mannose-receptor, Central Nervous System, myelin proteolipid protein[139-151], Encephalomyelitis, Autoimmune, Experimental, cell migration, Injections, Subcutaneous, animal experiment, Molecular Sequence Data, animal cell, delayed hypersensitivity, immunization, Severity of Illness Index, animal tissue, immunoglobulin G2, Mice, allergic encephalomyelitis, proteolipid protein, Cell Movement, T lymphocyte, Animals, C-type lectins, controlled study, Hypersensitivity, Delayed, Amino Acid Sequence, Myelin Proteolipid Protein, mouse, Cells, Cultured, nonhuman, EAE, Immunodominant Epitopes, animal model, drug effect, Th1 Cells, Peptide Fragments, unclassified drug, drug efficacy, cell proliferation, female, Self Tolerance, priority journal, Leukocytes, Mononuclear, Tolerance, Mannose
Abstract

SJL mice immunized with mannosylated (M-) PLP139-151 in complete adjuvant do not develop EAE and little CNS mononuclear cell infiltration; other mannosylated peptides were ineffective in this experimental setting. Despite apparently normal T cell responses, M-PLP139-151-immunized mice show impaired delayed-type-sensitivity to PLP139-151 but a normal response to other peptides. After re-immunization with PLP139-151 in complete adjuvant, these mice are largely tolerant to EAE, show less T cell proliferation and decreased peptide-specific IgG2a. Our data suggest that M-PLP139-151 induces peptide-specific tolerance to EAE via a mechanism of deletion or impaired migration of encephalitogenic T cells. © 2004 Elsevier B.V. All rights reserved. Chemicals / CAS: Immunodominant Epitopes; Mannose, 31103-86-3; Myelin Proteolipid Protein; Peptide Fragments; proteolipid protein 139-151

Published
2005

97. T-cell recognition of HLA-DQ2-bound gluten peptides can be influenced by an N-terminal proline at p-1

Author

Stepniak, D., Vader, L. W., Kooy, Y., van Veelen, P. A., Moustakas, A., Papandreou, N. A., Eliopoulos, E., Drijfhout, J. W., Papadopoulos, G. K., and Koning, F.

Subjects
HLA-DQ Antigens/genetics/*metabolism, T-Lymphocytes/*immunology, Molecular Sequence Data, Humans, Computer Simulation, Amino Acid Sequence, Databases, Protein, Lymphocyte Activation, Peptide Fragments/chemistry/immunology/metabolism, Epitopes, T-Lymphocyte/immunology, Glutens/chemistry/*immunology, Proline/*chemistry
Abstract

Recent research has implicated a large number of gluten-derived peptides in the pathogenesis of celiac disease, a preponderantly HLA-DQ2-associated disorder. Current evidence indicates that the core of some of those peptides is ten amino acids long, while HLA class II normally accommodates nine amino acids in the binding groove. We have now investigated this in detail, using gluten-specific T-cell clones, HLA-DQ2-specific peptide-binding assays and molecular modelling. T-cell recognition of both a gamma-gliadin peptide and a low-molecular-weight glutenin peptide was found to be strictly dependent on a ten-amino acids-long peptide. Subsequent peptide-binding studies indicated that the glutenin peptide bound in a conventional p1/p9 register, with an additional proline at p-1. Testing of substitution analogues demonstrated that the nature of the amino acid at p-1 strongly influenced T-cell recognition of the peptide. Moreover, molecular modelling confirmed that the glutenin peptide binds in a p1/p9 register, and that the proline at p-1 points upward towards the T-cell receptor. Database searches indicate that a large number of potential T-cell stimulatory gluten peptides with an additional proline at relative position p-1 exist, suggesting that the recognition of other gluten peptides may depend on this proline as well. This knowledge may be of importance for the identification of additional T-cell stimulatory gluten peptides and the design of a peptide-based, tolerance-inducing therapy. Immunogenetics

Published
2005

99. A novel and sensitive method for the detection of T cell stimulatory epitopes of α/β- and γ-gliadin

Author

Spaenij-Dekking, E.H.A., Kooy-Winkelaar, E.M.C., Nieuwenhuizen, W.F., Drijfhout, J.W., Koning, F., and TNO Voeding

Subjects
cereal, T-Lymphocytes, Epitopes, T-Lymphocyte, Lymphocyte Activation, Gliadin, Mice, wheat, triticale, epitope, analytic method, Mice, Inbred BALB C, quantitative analysis, T lymphocyte subpopulation, alcohol, article, food and beverages, Antibodies, Monoclonal, cell clone, trypsin, priority journal, CD4 antigen, Cell Division, animal experiment, Cereals, Enzyme-Linked Immunosorbent Assay, Binding, Competitive, Food technology, T lymphocyte activation, Animals, Humans, controlled study, human, mouse, Nutrition, nonhuman, food analysis, food, human cell, nutritional and metabolic diseases, barley, pepsin A, gliadin antibody, antigen detection, digestive system diseases, Peptide Fragments, rye, protein analysis, sensitivity and specificity, gluten, celiac disease
Abstract

Background: It is now generally accepted that coeliac disease (CD) is caused by inflammatory T cell responses to gluten peptides bound to HLA-DQ2 or -DQ8 molecules. There is overwhelming evidence that CD patients can mount T cell responses to peptides found in both α-gliadin and γ-gliadin molecules. Assays that would detect the presence or absence of such peptides in food would thus be accurate indicators of safely for consumption by CD patients. Aims: The development of a sensitive method to detect T cell stimulatory epitopes of α-gliadin and γ-gliadin molecules in food products. Methods: Monoclonal antibodies (mAb) were raised against peptides encoding the T cell stimulatory epitopes of α-gliadin (amino acids (aa) 59-71) and aa γ-gliadin (aa 142-153 and aa 147-159). These mAb competition assays were developed that quantitatively detect T cell stimulatory epitopes present on both intact proteins and peptides of sizes recognisable by CD4+ T cells. Results: With the mAb based competition assays, T cell epitopes were detected in pepsin/trypsin digests of wheat proteins and ethanol extracts of various food products, with detection levels lower than those reached with gluten specific T cells. Moreover, the presence of T cell stimulatory epitopes was also detected in preparations of barley, rye, and triticale, other cereals known to be toxic for CD patients. Conclusions: A new antibody based method has been developed, detecting the presence of T cell stimulatory gluten peptides. This can be used to further ensure the safety of food consumed by CD patients.

Published
2004

100. Bacterial immune modulation of the cytokine response elicited by gliadin in an in vitro model ofceliac disease

Author

Pozo Rubio, Tamara, Marcos, Ascensión, Koning, F., Mujico, Jorge R., Sanz Herranz, Yolanda, Nova, Esther, Pozo Rubio, Tamara, Marcos, Ascensión, Koning, F., Mujico, Jorge R., Sanz Herranz, Yolanda, and Nova, Esther

Abstract

Gluten peptides have been shown to induce cytotoxicity and IL-15 production even in in vitro studies with cell lines and biopsies of healthy subjects(1,2). We hypothesized that the inflammatory milieu caused by gluten antigens might be counteracted by certain species or strains of the commensal intestinal microbiota in interaction with the immune system. The aim of the present study was to evaluate the effect of different bacterialstrains from breastfed (BF) and formula-fed (FF) infants at risk ofceliac disease on cytokine production and T cell proliferationin vitro. Two combinations of predominant bacteria from fecal samples ofBF (Escheriquia coli (51.6%), Lactobacillus casei (19.4%), and Bifidobacterium breve (29%)) and FF (Klebsiella pneumoniae (44.1%), Lactobacillus rhamnosus (29.4%), and Bifidobacterium longum (26.5%)) infants were used. Caco-2 monolayers grown in a transwell cell-culture system (12mm inserts (Millipore)) were challenged by apical addition of 2 · 106cfu/insert ofbacteria. PBMCs (1 · 106 cells/well) and gluten specific T cell clones (1 · 105 cells/well) from HLA-DQ2 patients were added in the basal compartment of the culture well for a 12-hour incubation.Gliadin (7.5 mg/mL) was also added at the same time in the basal or apical compartment. Thereafter, further 36 hours incubation was allowed after disassembly of the system in order to measure the cytokine production by the sensitized Caco-2, and cytokine production and proliferation by T cell clones separately.TNF-a, IL-6, IL-1b, and IL-8 cytokines were measured in Caco-2 cells basolateral medium, and TNF-a, IL-6, IL-1b, and IL-10 cytokines were measured in T cells supernatant by Cytometric Bead Array Flex sets (BD Biosciences) and analyzed by flow cytometry. T cell proliferation was measured by quantification of H3-thymidine incorporation. Gliadin in the apical compartment did not show any effect on T cell proliferation and cytokine production. In the basal compartment Gliadin plus breastfed mi

Published
2013

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