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1. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial

Author

Yañez, Anahí, Fernández, Marcelo, Tolcachier, Alberto, Belloni, Juan, Taborda, Jorge, De Salvo, Maria, Maspero, Jorge, Victorio, Carlos, Navarta, Miguel Chirino, Grilli, Monica, Rodríguez, Pablo, Otaola, María, Cambursano, Víctor, Malamud, Patricia, Stok, Ana, Arce, German, Roza, Osiris, Scherbovsky, Fernando, Elias, Pedro, Saez, Maria Salazan, Peters, Matthew, Phillips, Martin, Upham, John, Gibson, Peter, Thien, Francis, Douglass, Jo, Thomas, Paul, Bardin, Philip, Sajkov, Dimitar, Hew, Mark, Langton, David, Pez, Andreia, Fritscher, Carlos, Hetzel, Jorge, Mattos, Waldo, Stelmach, Rafael, Antila, Martti, Fernandes, Ana Luisa, Metev, Hristo, Ivanov, Yavor, Bogdanova, Aneliya, Markova, Ana Dancheva, Peneva, Marinka, Veselinova, Rumyana, Petkova, Tatyana, Petrova, Vanushka, Shopova, Elena, Ivanova, Yuliya, Yotsova, Rumyana, Kirkova, Ginka, Petrova, Galina, Dachev, Svetoslav, Sotirova, Kostadinka, Stoyanova, Mariyana, Yakov, Oleg, Ilieva-Fartunova, Vanya, Lemiere, Catherine, Laviolette, Michel, Yang, William, FitzGerald, J Mark, Pek, Bonavuth, Killorn, William Patrick, Poirier, Claude, Chouinard, Guy, Melenka, Lyle, Leigh, Richard, Nair, Parameswaran, Dorscheid, Delbert, Martin, James, Pavie, Juana, Rosenblut, Andres, Cartagena, Claudia, Quilodran, Carlos, Muñoz, Silvia, Malkusova, Ivana, Veverka, Josef, Holub, Stanislav, Mares, Jaroslav, Kozel, Radovan, Kopecka, Daniela, Zindr, Vladimir, Cerva, Pavel, Chanez, Pascal, Bourdin, Arnaud, Devouassoux, Gilles, Taille, Camille, De Blay, Frédéric, Goupil, Francois, Leroyer, Christophe, Gourcerol, Delphine, Didi, Toufik, Didier, Alain, Garcia, Gilles, Bonniaud, Philippe, Vasram, Riazate Rossanaly, Lommatzsch, Marek, Harnest, Ulf, Linnhoff, Anneliese, Keller, Claus, Hoheisel, Gerhard, Förster, Karin, Schultz, Thomas, Schenkenberger, Isabelle, Kirschner, Joachim, Schmoller, Tibor, Zielen, Stefan, Kornmann, Marc, Beck, Ekkehard, Volgmann, Lutz, Dichmann, Rolf, Overlack, Axel, Winkler, Jörg, Mikloweit, Petra, Ballenberger, Sabine, Rolke, Mathias, Korn, Stephanie, Pabel, Helmut, Hoffmann, Martin, Feimer, Jan, Rabe, Klaus, Deckelmann, Regina, Welte, Tobias, Ohbayashi, Hiroyuki, Hozawa, Soichiro, Shimoda, Terufumi, Yoshida, Makoto, Nagakura, Toshikazu, Kamei, Tadashi, Sano, Yasuyuki, Kagami, Shinichiro, Takahashi, Hisaho, Haida, Michiko, Kimura, Goro, Nakamura, Hiroyuki, To, Yasuo, Shinkai, Masaharu, Shimokawaji, Tadasuke, Kudo, Makoto, Shijyubo, Noriharu, Tochigi, Takao, Kato, Motokazu, Tanaka, Akihiko, Gon, Yasuhiro, Sasaki, Norihisa, Ohdaira, Tetsuro, Omori, Chiharu, Takahashi, Toshiki, Takeuchi, Satomi, Nakajima, Kiyotaka, Makita, Hironi, Kaneko, Masahiro, Furuta, Kenjiro, Taniguchi, Masami, Inobe, Yoshito, Miki, Hiroshi, Nakamura, Yoichi, Miyazawa, Naoki, Yano, Shuichi, Iijima, Masayuki, Yamato, Tsuyoshi, Diaz, Javier, Matsuno, Alberto, Felix, Efrain, Guerreros, Alfredo, Daly, Alejandro, Rodriguez Chariarse, Fernando, Salazar, Danilo, Castro, Socorro, Chavez, William, Estrella, Rolando, Aquino, Teresita, Atienza, Tito, Samoro, Ronnie, Isidro, Marie Grace Dawn, Kuna, Piotr, Antczak, Adam, Bednarek, Michał, Mądra-Rogacka, Danuta, Hofman, Teresa, Jutel, Marek, Pisarczyk-Bogacka, Ewa, Kot, Agata, Mróz, Robert, Czupryńska-Borkowska, Małgorzata, Żurowska-Gębala, Małgorzata, Dyczek, Andrzej, Jasieniak-Pinis, Grażyna, Wojnowski, Piotr, Trębas-Pietraś, Ewa, Dobryniewska, Małgorzata, Stobiecki, Marcin, Tarnowska-Matusiak, Marzenna, Magner, Alina, Kolczyński, Andrzej, Kachel, Tomasz, Bartuzi, Zbigniew, Majorek-Olechowska, Bernadetta, Śliwiński, Paweł, Balicka, Violetta, Hajoł, Elżbieta, Stachera, Jacek, Rachel, Marta, Michnar, Marek, Tałałaj, Jarosław, Springer, Ewa, Napora, Piotr, Grzelewski, Tomasz, Bijata-Bronisz, Renata, Świderska, Anna, Mincewicz, Grzegorz, Sankowski, Zbigniew, Fijołek, Tomasz, Kwaśniewski, Artur, Jerzyńska, Joanna, Cygler, Jerzy, Olesiejuk, Ryszard, Von Steiner, Iwona, Machowiak, Wojciech, Filipek, Krzysztof, Piskorz, Piotr, Uhryn, Ewa, Nittner-Marszalska, Marita, Rybicka-Liszewska, Elżbieta, Bodzenta-Łukaszyk, Anna, Chełmińska, Marta, Krupa-Borek, Izabella, Skucha, Wojciech, Płoszczuk, Anna, Mihaescu, Traian, Petrui, Ioan Dorin, Savu, Angelica, Apti, Ghiulten, Toma, Claudia, Trailescu, Ana, Sokurenko, Sergei, Trofimov, Vasiliy, Leshchenko, Igor, Shaporova, Natalia, Ilyashevich, Inna, Stitsenko, Irina, Vizel, Alexander, Ilkovich, Yulia, Tikhanov, Dmitrii, Goncharova, Svetlana, Ezhov, Andrey, Ignatova, Galina, Izmozherova, Nadezhda, Berdnikova, Nadezhda, Goryachkina, Ludmila, Popova, Veronika, Bolieva, Laura, Rebrov, Andrey, Nosov, Vladimir, Magnitskaya, Olga, Nedogoda, Sergey, Abrosimov, Vladimir, Molotkov, Artem, Reshedko, Galina, Smirnov, Mikhail, Osipenko, Marina, Pavlysh, Elena, Myasoedova, Svetlana, Lenskaya, Liudmila, Chistyakov, Valery, Vishneva, Elena, Uon, Liliya, Zateyschikova, Anna, Laleko, Svetlana, Pak, Tatiana, Bruning, Axel, Naidoo, Visvakuren, Reddy, Jeevren, Van Zyl Smit, Richard, Park, Hae-Sim, Cho, Young Joo, Cho, Sang-Heon, Lee, Sang Haak, Lee, Byung Jae, Kim, Ju Sang, Cho, You Sook, Park, Choon-Sik, Kim, Mi-Kyeong, Koh, Young-Il, Kim, Joo-Hee, Lee, Sook Young, Lee, Sang Pyo, Park, Jung Won, Yoo, Kwang Ha, Yoon, Hyoungkyu, Lee, Jaechun, Hur, Gyu-Young, Lee, Soo Keol, Kim, HeeKyoo, Ramos Barbón, David, Laffond Yges, Elena, Martínez Moragón, Eva, Arias Guillen, Miguel, Saura Vinuesa, Alberto, Sánchez-Toril López, Fernando, Velasco Garrido, José Luis, García-Cosio Piqueras, Borja, Pérez de Llano, Luis, Valero Santiago, Antonio Luis, Rubio, Myriam Calle, Bjermer, Leif, Lundbäck, Bo, Gemicioglu, Bilun, Bavbek, Sevim, Ediger, Dane, Erdinc, Munevver, Hanta, Ismail, Nayci, Sibel, Arinc, Sibel, Iashyna, Liudmyla, Mostovoy, Yuriy, Ostrovskyy, Mykola, Kuryk, Lesia, Lemko, Ivan, Ospanova, Tetyana, Moskalenko, Liubov, Korzh, Oleksii, Blazhko, Viktor, Krakhmalova, Olena, Romaniuk, Liliia, Dytyatkovs'ka, Yevgeniya, Yakovenko, Oleh, Gavrysyuk, Volodymyr, Burhan, Hassan, Saralaya, Dinesh, Scott, Stephen, Morice, Alyn, Jackson-Voyzey, Ewart, Win, Thida, Nasser, Shuab, Harrison, Richard, Chaudhuri, Rekha, Nordstrom, Monica, De, Pradip, Masoli, Matthew, Mansur, Adel, Gunstone, Anthony, Niven, Robert, Harrison, Timothy, Babu, Suresh, Bhuchar, Subodh, Kureishy, Shahrukh, Zwetchkenbaum, John, Kaplan, Lawrence, Bleecker, Eugene, Reyes, Santiago, Fakih, Faisal, Heuer, Marvin, Klein, Ryan, Marcus, Michael, Hussain, Iftikhar, Tanus, Tonny, Raissy, Hengameh, Alpizar, Sady, Rodriguez, Hector, Gleich, Gerald, Bridges, Tracy, Pouzar, Joe, Steven, Gary, Matz, Jonathan, Krstevska, Shana, Ziworitin, Dama, Kaplan, Adolfo, Sublett, James, DeAngelo, James, Darter, Amy, Agaiby, John, Hagan, John, Davis, Enrique, Siri, Dareen, Mcevoy, Charlene, Dharma, Chrisette, Karimjee, Najmuddin, Kelsen, Steven, Frade, Manuel, Silverthorn, Amy, Kline, Joel, Averill, Francis, Ruiz, Jose, Robinette, Emory, Shaikh, Zeeshan, Aguilar, Carlos, Nish, William, Alvarez, German, Ismail, Younus, Parikh, Purvi, Leong, Mila, Murphy, Dennis, Garcia, Francisco, Goldsobel, Alan, Blanco, Antonio, Campbell, Edward, Perez, Guido, Chupp, Geoffrey, Bates, Toby, Perez, Vandely, Wenzel, Sally, Shenoy, Kartik, Katial, Rohit, Bernstein, David, Parikh, Neil, Sims, William, Ferguson, Gary, Pham, David, George, Anu, Beasley, Richard, Perez, Gilberto, Garver, Robert, Garcia-Portela, Miriam, Wong, Stephen, Soong, Weily, Guillot, Richard, Hudes, Golda, Arif, Ahmed, Binker, Josefa, Villareal, Manuel, Ziegner, Ulrike, Ojile, Joseph, Goswami, Sanjeev, Piniella, Carlos, Segal, Ilia, Zafra, Heidi, Lee, Mitchell, Tarpay, Martha, Panuto, John, Merchant, Rajan, Springsteen, Peter, Scialla, Timothy, Shapero, Paul, Allen, Karen, Moss, Mark, Cruz, Humberto, Rumbyrt, Jeffrey, Boyd, Amy, Nathan, Robert, Bernstein, Jonathan, Jacobs, Joshua, Ginchansky, Elliot, Johnston, Janice, Baxter, Barbara, Johnson II, Thomas, Apaliski, Stephen, Corder, Clinton, Fuentes, David, Diaz, Joseph, Ngo, Chau, Le, Lan, Busse, William W, Bleecker, Eugene R, Ferguson, Gary T, Barker, Peter, Sproule, Stephanie, Olsson, Richard F, Martin, Ubaldo J, and Goldman, Mitchell

Published
2019
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7. Concentrations of plasminogen activator inhibitor-1 (PAI-1) and urokinase plasminogen activator (uPA) in induced sputum of asthma patients after allergen challenge.

Author

Marcin Moniuszko, Krzysztof Kowal, Sebastian Zukowski, and Anna Bodzenta-Lukaszyk

Subjects
Cytology, QH573-671
Abstract

Urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) are involved in tiisue remodeling and repair processes associated with acute and chronic inflammation. The aim of the study was to evaluate the effect of allergen challenge on concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs). Thirty HDM-AAs and ten healthy persons (HCs)were recruited for the study. In 24 HDM-AAs bronchial challenge with Dermatophagoides pteronyssinus (Dp) and in 6 HDM-AAs sham challenege with saline were performed. In HDM-AAs sputum was induced 24 hours before (T0) and 24 hours (T24) after the challenge. Concentration of uPA and PAI-1 in induced sputum were determined using immunoenzymatic assays. At T0 in HDM-AAs mean sputum uPA (151 Âą 96 pg/ml) and PAI-1 (4341 Âą 1262 pg/ml) concentrations were higher than in HC (18.8 Âą 6.7 pg/ml; p=0.0002 and 596 Âą 180 pg/ml; p

Published
2011
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8. Concentrations of plasminogen activator inhibitor-1 (PAI-1) and urokinase plasminogen activator (uPA) in induced sputum of asthma patients after allergen challenge

Author

Krzysztof Kowal,, Marcin Moniuszko, Sebastian Zukowski, and Anna Bodzenta-Lukaszyk

Subjects
plasminogen activator inhibitor, urokinase, asthma, allergen challenge, Cytology, QH573-671
Abstract

Urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) are involved in tiisue remodeling and repairprocesses associated with acute and chronic inflammation. The aim of the study was to evaluate the effect of allergen challengeon concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs). ThirtyHDM-AAs and ten healthy persons (HCs)were recruited for the study. In 24 HDM-AAs bronchial challenge with Dermatophagoidespteronyssinus (Dp) and in 6 HDM-AAs sham challenege with saline were performed. In HDM-AAs sputumwas induced 24 hours before (T0) and 24 hours (T24) after the challenge. Concentration of uPA and PAI-1 in induced sputumwere determined using immunoenzymatic assays. At T0 in HDM-AAs mean sputum uPA (151±96 pg/ml) and PAI-1(4341±1262 pg/ml) concentrations were higher than in HC (18.8±6.7 pg/ml; p=0.0002 and 596±180 pg/ml; p

Published
2010

11. The concentration of kynurenine in rat model of asthma.

Author

Barbara Mroczko, Anna Tankiewicz-Kwedlo, Dariusz Pawlak, Irena Kasacka, Iwona Kucharewicz, Wlodzimierz Buczko, and Anna Bodzenta-Lukaszyk

Subjects
Cytology, QH573-671
Abstract

Asthma is a chronic inflammatory disease that involves the immune system activation. Evidence is accumulating about the role of kynurenine pathway in the immune system regulation. The kynurenine pathway includes several metabolites of tryptophan, among others kynurenine (KYN). To study the immunological system regulation in asthma a simple and sensitive models of asthma are required. In the present study we induced rat model of asthma using ovalbumin (OVA) sensitization followed by challenge with OVA. The development of asthma has been confirmed by plasma total IgE measurement and the histological examination. The concentration of KYN has been determined in plasma, lungs and liver by high-performance liquid chromatography (HPLC). In OVA sensitized rats the concentration of total IgE was statistically significantly increased as compared to VEH sensitized control groups (437.6 +/- 97.7 kU/l vs 159.2 +/- 22.7 kU/l, respectively; p< 0.01). In asthmatic animals, the number of eosinophils, neutrophils and mast cells increased considerably, and epithelial lesion and the increase in airway epithelium goblet cells and edema of bronchial mucosa were present. We did not observe any significant changes in the concentration of KYN in plasma, lungs or liver between studied groups. In conclusion, the concentration of KYN remains unchanged in asthmatic animals as compared to control groups. Further studies using rat model of asthma are warranted to establish the role of kynurenine pathway regulation in asthma.

Published
2008
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15. Bronchial macrophages in asthmatics reveal decreased CD16 expression and substantial levels of receptors for IL-10, but not IL-4 and IL-7.

Author

Milena Dabrowska, Krzysztof Kowal, Anna Bodzenta-Lukaszyk, and Marcin Moniuszko

Subjects
Cytology, QH573-671
Abstract

The role of different subpopulations of bronchial macrophages (BMs) in asthma pathogenesis has not yet been completely elucidated. In addition, little is known about potential in vivo responsiveness of BMs to pro- and anti-inflam-matory cytokines present in the bronchial milieu. We aimed to characterize asthmatic patients' BM subpopulations delineated by common markers of macrophage/monocyte cells, CD16 and CD14, and subsequently to analyze cytokine receptor expression on those subsets. Subjects included eighteen patients with moderate asthma (six steroid-naive and twelve steroid-treated) and ten healthy control subjects. Flow cytometry was used to analyze phenotypical features of BMs including expression of receptors for IL-10, IL-4 and IL-7. Exhaled nitric oxide analysis and induced sputum eosinophil counts were used to assess airway inflammation. BMs from both steroid-naive and steroid-treated asthmatic patients showed significantly decreased expression of CD16, as compared to healthy subjects' BMs. CD16, but not CD14, expression inversely correlated with exhaled nitric oxide levels and sputum eosinophilia. Short-term administration of inhaled cortiocosteroids (ICS) in steroid-naive asthmatic patients led to significant reduction of CD16 expression and enhancement of CD14 expression. Next, we analyzed the expression of receptors for IL-10, IL-4 and IL-7 on the surface of BM subpopulations characterized by different levels of CD14 and CD16 expression. We observed substantial levels of IL-10R on the surface of BMs collected from asthmatic and healthy subjects. Interestingly, IL-10R was found mostly on those macrophages that co-expressed CD14. In contrast, independently on co-expression of CD14, the levels of IL-4R and IL-7R on BMs were low in both asthmatic and healthy subjects. The results suggest that different BM subsets may be differentially involved in regulating the inflammatory response in allergic asthma.

Published
2007
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17. Predictors of side effects during the buildup phase of venom immunotherapy for Hymenoptera venom allergy: The importance of baseline serum tryptase †

Author

Ruëff, Franziska, Przybilla, Bernhard, Biló, Maria Beatrice, Müller, Ulrich, Scheipl, Fabian, Aberer, Werner, Birnbaum, Joëlle, Bodzenta-Lukaszyk, Anna, Bonifazi, Floriano, Bucher, Christoph, Campi, Paolo, Darsow, Ulf, Egger, Cornelia, Haeberli, Gabrielle, Hawranek, Thomas, Kucharewicz, Iwona, Küchenhoff, Helmut, Lang, Roland, Quercia, Oliviero, Reider, Norbert, Severino, Maurizio, Sticherling, Michael, Sturm, Gunter Johannes, and Wüthrich, Brunello

Published
2010
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20. Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: Importance of baseline serum tryptase—a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity

Author

Ruëff, Franziska, Przybilla, Bernhard, Biló, Maria Beatrice, Müller, Ulrich, Scheipl, Fabian, Aberer, Werner, Birnbaum, Joëlle, Bodzenta-Lukaszyk, Anna, Bonifazi, Floriano, Bucher, Christoph, Campi, Paolo, Darsow, Ulf, Egger, Cornelia, Haeberli, Gabrielle, Hawranek, Thomas, Körner, Michael, Kucharewicz, Iwona, Küchenhoff, Helmut, Lang, Roland, Quercia, Oliviero, Reider, Norbert, Severino, Maurizio, Sticherling, Michael, Sturm, Gunter Johannes, and Wüthrich, Brunello

Published
2009
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25. Clinical effectiveness of hymenoptera venom immunotherapy: a prospective observational multicenter study of the European academy of allergology and clinical immunology interest group on insect venom hypersensitivity.

Author

Franziska Ruëff, Bernhard Przybilla, Maria Beatrice Biló, Ulrich Müller, Fabian Scheipl, Michael J Seitz, Werner Aberer, Anna Bodzenta-Lukaszyk, Floriano Bonifazi, Paolo Campi, Ulf Darsow, Gabrielle Haeberli, Thomas Hawranek, Helmut Küchenhoff, Roland Lang, Oliviero Quercia, Norbert Reider, Peter Schmid-Grendelmeier, Maurizio Severino, Gunter Johannes Sturm, Regina Treudler, and Brunello Wüthrich

Subjects
Medicine, Science
Abstract

BackgroundTreatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors.ObjectiveOur aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase.MethodsIn this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models.Results22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios InterpretationIt is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy.

Published
2013
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26. Decreased CD127 Expression on CD4+ T-Cells and Elevated Frequencies of CD4+CD25+CD127− T-Cells in Children with Long-Lasting Type 1 Diabetes

Author

Marcin Moniuszko, Barbara Glowinska-Olszewska, Malgorzata Rusak, Marta Jeznach, Kamil Grubczak, Danuta Lipinska, Robert Milewski, Anna Justyna Milewska, Milena Dabrowska, Ewa Jablonska, Adam Kretowski, Maria Gorska, Anna Bodzenta-Lukaszyk, and Artur Bossowski

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Pathobiology of type 1 diabetes (T1D) is predominantly associated with T-cell-related actions. Homeostasis of majority of T-cells is critically dependent on signals mediated by CD127 (interleukin-7 receptor, IL-7R). In contrast, regulatory T-cells express very little CD127 and thereby may be delineated by CD4+CD25+CD127− phenotype. Here we aimed to analyze CD127 expression on CD4+ and CD8+ T-cells and enumerate CD4+CD25+CD127− T-cells in long-lasting T1D. T-cells were analyzed by flow cytometry and immunologic data were correlated with vascular, metabolic, and inflammatory parameters. We demonstrated significantly decreased CD127 levels on CD4+, but not CD8+, T cells in T1D pediatric patients. Interestingly, frequencies of CD4+CD25+CD127− T-cells were significantly enhanced in T1D children and correlated well with frequencies of CD34+CD144+ endothelial progenitor cells and CD4+CD25− T-cells. Levels of CD127 on both CD4+ and CD8+ T-cells in T1D patients were not correlated to each other or HbA1C. Interestingly, however, CD127 levels on CD4+ T-cells were significantly correlated to frequencies of CD4+CD25+CD127− T-cells, whereas CD127 levels on CD8+ T-cells were significantly correlated to concentrations of VEGF and triglycerides. Our data indicate that CD127 expression is differentially modulated on CD4+ and CD8+ T-cells in the course of T1D. Moreover, we demonstrated that, in contrast to recent-onset T1D, long-lasting T1D is associated with enhancement of T-cells with regulatory phenotype.

Published
2013
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27. Short-term effects of wasp-venom immunotherapy on the expression of the receptor for interleukin-7 (IL-7) on peripheral blood CD4+ T cells

Author

Maria Magdalena Tomasiak-Łozowska, Kamil Grubczak, Marcin Moniuszko, Maciej Klimek, Andrzej Eljaszewicz, Aleksandra Starosz, Marcin Czaban, and Anna Bodzenta-Lukaszyk

Subjects
business.industry, Immunology, General Earth and Planetary Sciences, Specific immunotherapy, Medicine, Interleukin, Venom immunotherapy, Receptor, business, Peripheral blood, General Environmental Science
Published
2019
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32. Zonulin, inflammation and iron status in patients with early stages of chronic kidney disease

Author

Jolanta Malyszko, Ewelina Lukaszyk, Ewa Koc-Zorawska, Mateusz Lukaszyk, and Anna Bodzenta-Lukaszyk

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, Cholera Toxin, Anemia, Urology, Iron, 030232 urology & nephrology, Hepcidin, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Hepcidins, Diabetes mellitus, Internal medicine, Chronic kidney disease, Receptors, Transferrin, medicine, Nephrology - Original Paper, Humans, Protein Precursors, Renal Insufficiency, Chronic, Soluble transferrin receptor, Aged, Inflammation, Aged, 80 and over, Intestinal permeability, biology, Haptoglobins, business.industry, Interleukin-6, Zonulin, Middle Aged, medicine.disease, Ferritin, 030104 developmental biology, C-Reactive Protein, Nephrology, Case-Control Studies, biology.protein, business, Biomarkers, Kidney disease
Abstract

Background/aims Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters. Methods Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study. Zonulin, hepcidin-25, soluble transferrin receptor, interleukin-6 and high-sensitivity C-reactive protein were measured using commercially available assays. Results Zonulin was significantly lower among patients with CKD in comparison with healthy volunteers. There were no statistically significant differences in zonulin concentration between patients with and without inflammation. Zonulin was significantly correlated with hepcidin only in patients with inflammation. Zonulin was neither related to iron nor related to ferritin. Conclusions Zonulin cannot be considered as an inflammatory marker in CKD. It does not play a role in the disturbances of iron metabolism in CKD. Its physiological role remains to be elucidated.

Published
2017

46. High-dose bee venom exposure induces similar tolerogenic B-cell responses in allergic patients and healthy beekeepers

Author

Tadech Boonpiyathad, Andrzej Eljaszewicz, Milena Sokolowska, Norbert Meyer, Oliver F. Wirz, W. van de Veen, M. M. Tomasiak-Lozowska, Marcin Moniuszko, Kiat Ruxrungtham, and Anna Bodzenta-Lukaszyk

Subjects
0301 basic medicine, Regulatory B cells, Immunology, B-Lymphocyte Subsets, Dose-Response Relationship, Immunologic, Biology, Lymphocyte Activation, Immunoglobulin E, Immunophenotyping, Immune tolerance, 03 medical and health sciences, Occupational Exposure, Hypersensitivity, Immune Tolerance, medicine, Humans, Immunology and Allergy, IL-2 receptor, B cell, B-Lymphocytes, Environmental Exposure, Environmental exposure, Allergens, Immunoglobulin A, Bee Venoms, Phospholipases A2, Tolerance induction, 030104 developmental biology, medicine.anatomical_structure, Desensitization, Immunologic, Immunoglobulin G, biology.protein, Cytokines, Antibody, Biomarkers
Abstract

Background The involvement of B cells in allergen tolerance induction remains largely unexplored. This study investigates the role of B cells in this process, by comparing B-cell responses in allergic patients before and during allergen immunotherapy (AIT) and naturally exposed healthy beekeepers before and during the beekeeping season. Methods Circulating B cells were characterized by flow cytometry. Phospholipase A2 (PLA)-specific B cells were identified using dual-color staining with fluorescently labeled PLA. Expression of regulatory B-cell-associated surface markers, interleukin-10, chemokine receptors, and immunoglobulin heavy-chain isotypes, was measured. Specific and total IgG1, IgG4, IgA, and IgE from plasma as well as culture supernatants of PLA-specific cells were measured by ELISA. Results Strikingly, similar responses were observed in allergic patients and beekeepers after venom exposure. Both groups showed increased frequencies of plasmablasts, PLA-specific memory B cells, and IL-10-secreting CD73- CD25+ CD71+ BR 1 cells. Phospholipase A2-specific IgG4-switched memory B cells expanded after bee venom exposure. Interestingly, PLA-specific B cells showed increased CCR5 expression after high-dose allergen exposure while CXCR4, CXCR5, CCR6, and CCR7 expression remained unaffected. Conclusions This study provides the first detailed characterization of allergen-specific B cells before and after bee venom tolerance induction. The observed B-cell responses in both venom immunotherapy-treated patients and naturally exposed beekeepers suggest a similar functional immunoregulatory role for B cells in allergen tolerance in both groups. These findings can be investigated in other AIT models to determine their potential as biomarkers of early and successful AIT responses.

Published
2016
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48. Fluticasone/formoterol combination therapy is as effective as fluticasone/salmeterol in the treatment of asthma, but has a more rapid onset of action: an open-label, randomized study

Author

McAulay Kirsten, Dymek Andrzej, Bodzenta-Lukaszyk Anna, and Mansikka Heikki

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Background The inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) and the long-acting β2-agonist (LABA) formoterol fumarate (formoterol) are being made available as a combination product (fluticasone/formoterol, flutiform®) in a single aerosol inhaler. This 12-week, open-label, randomized, active-controlled, parallel-group, multicentre, phase 3 study compared the efficacy and safety of fluticasone/formoterol with the commercially available combination product fluticasone/salmeterol. Methods Patients aged ≥ 18 years (N = 202) with mild-to-moderate–severe, persistent asthma for ≥ 6 months prior to screening were included in the study. After a screening phase (4–10 days), eligible patients were randomized 1:1 to receive fluticasone/formoterol or fluticasone/salmeterol during the 12-week treatment period. The primary objective was to demonstrate non-inferiority of fluticasone/formoterol versus fluticasone/salmeterol, measured by pre-dose forced expiratory volume in the first second (FEV1), at week 12. Results Fluticasone/formoterol was comparable to fluticasone/salmeterol for the primary efficacy endpoint, mean pre-dose FEV1 at week 12. The new combination was also comparable to fluticasone/salmeterol for change from baseline to week 12 in pre-dose FEV1, change from pre-dose FEV1 at baseline to 2-hour post-dose FEV1 at week 12 and discontinuations due to lack of efficacy. Importantly, fluticasone/formoterol was superior to fluticasone/salmeterol in time to onset of action throughout the duration of the study. The two treatments demonstrated similar results for various other secondary efficacy parameters, including other lung function tests, patient-reported outcomes, rescue medication use, asthma exacerbations and Asthma Quality of Life Questionnaire scores. Fluticasone/formoterol was well tolerated and had a good safety profile that was similar to fluticasone/salmeterol. Conclusions The results of this study indicate that fluticasone/formoterol is as effective as fluticasone/salmeterol, and has a more rapid onset of action, reflecting the faster bronchodilatory effects of formoterol compared with those of salmeterol. If patients perceive the benefits of therapy with fluticasone/formoterol more rapidly than with fluticasone/salmeterol, this could have a positive impact on preference and adherence. Trial Registration ClinicalTrials.gov: NCT00476073

Published
2011
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49. Eotaxin-1 in exhaled breath condensate of stable and unstable asthma patients.

Author

Zietkowski Ziemowit, Tomasiak-Lozowska Maria M, Skiepko Roman, Zietkowska Elzbieta, and Bodzenta-Lukaszyk Anna

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Airway eosinophilia is considered a central event in the pathogenesis of asthma. Eotaxin plays a key role in selective eosinophil accumulation in the airways and, subsequently, their activation and degranulation. The study was undertaken to evaluate eotaxin-1 levels in the exhaled breath condensate (EBC) of asthmatics with different degrees of asthma severity and to establish the possible correlation of these measurements with other recognized parameters of airway inflammation. Methods EBC was collected from 46 patients with allergic asthma (14 with steroid-naïve asthma, 16 with ICS-treated, stable asthma, 16 with ICS-treated unstable asthma) and 12 healthy volunteers. Concentrations of eotaxin-1 were measured by ELISA. Results In the three groups of asthmatics, eotaxin-1 concentrations in EBC were significantly higher compared with healthy volunteers (steroid-naïve asthma: 9.70 pg/ml ± 1.70, stable ICS-treated asthma: 10.45 ± 2.00, unstable ICS-treated asthma: 17.97 ± 3.60, healthy volunteers: 6.24 ± 0.70). Eotaxin-1 levels were significantly higher in patients with unstable asthma than in the two groups with stable disease. We observed statistically significant correlations between the concentrations of eotaxin-1 in EBC and exhaled nitric oxide (FENO) or serum eosinophil cationic protein (ECP) in the three studied groups of asthmatics. We also discovered a significantly positive correlation between eotaxin-1 in EBC and blood eosinophil count in the groups of patients with unstable asthma and steroid-naïve asthma. Conclusions Measurements of eotaxin-1 in the EBC of asthma patients may provide another useful diagnostic tool for detecting and monitoring airway inflammation and disease severity.

Published
2010
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50. Fibroblast growth factor 23, iron and inflammation – are they related in early stages of chronic kidney disease?

Author

Ewelina Lukaszyk, Ewa Koc-Zorawska, Jolanta Malyszko, Anna Bodzenta-Lukaszyk, and Mateusz Lukaszyk

Subjects
Fibroblast growth factor 23, medicine.medical_specialty, 030232 urology & nephrology, Renal function, Fibrinogen, fibroblast growth factor 23, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, iron, Hepcidin, Clinical Research, Internal medicine, Medicine, 030212 general & internal medicine, Soluble transferrin receptor, Creatinine, biology, Transferrin saturation, business.industry, General Medicine, medicine.disease, Endocrinology, chemistry, inflammation, biology.protein, business, chronic kidney disease, Kidney disease, medicine.drug
Abstract

INTRODUCTION Fibroblast growth factor 23 (FGF-23) levels are elevated in impaired renal function. Inflammation and iron are potential regulators of FGF-23. The aim of the study was to evaluate the association between FGF-23 concentration, novel iron status biomarkers and inflammatory parameters among patients with early stages of chronic kidney disease (CKD). MATERIAL AND METHODS The study population included 84 patients with CKD in the early stage. Serum hemoglobin, fibrinogen, creatinine, iron, transferrin saturation and ferritin levels were measured using standard laboratory methods. Commercially available kits were used to measure: intact FGF-23, hepcidin, soluble transferrin receptor (sTfR), interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP). RESULTS In patients with CKD no differences in FGF-23 concentration according to iron status were observed. Lower iron concentration was associated with higher concentrations of hsCRP, IL-6 and fibrinogen. In univariate and multivariate analysis FGF-23 correlated with fibrinogen (r = -0.23, p < 0.05) and eGFR (r = -0.36, p < 0.05). CONCLUSIONS FGF-23 is affected by kidney function and fibrinogen but not iron status parameters in the early stages of CKD. Our data are paving the way for further studies on the role of FGF-23 in iron metabolism, especially in early stages of CKD.

Published
2016

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