44 results on '"Quinti, I"'
Search Results
2. The response to BTN62b2 booster doses demonstrates that serum antibodies do not predict the establishment of immune B-cell memory in common variable immune deficiencies
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Piano Mortari, E., primary, Pulvirenti, F., additional, Marcellini, V., additional, Terreri, S., additional, Fernandez Salinas, A., additional, Ferrari, S., additional, Di Napoli, G., additional, Guadagnolo, D., additional, Sculco, E., additional, Albano, C., additional, Guercio, M., additional, Di Cecca, S., additional, Milito, C., additional, Garzi, G., additional, Pesce, A.M., additional, Bonanni, L., additional, Sinibaldi, M., additional, Di Cecilia, S., additional, Agrati, C., additional, Quintarelli, C., additional, Zaffina, S., additional, Locatelli, F., additional, Carsetti, R., additional, and Quinti, I., additional
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- 2022
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3. Traitement par immunoglobuline sous cutanée facilitée chez les patients atteints de déficit immunitaire primitif et secondaire : l’étude FIGARO
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Borte, M., primary, Hanitsch, L., additional, Mahlaoui, N., additional, Fasshauer, M., additional, Huscher, D., additional, Speletas, M., additional, Dimou, M., additional, Kameniak, M., additional, Pittrow, D., additional, and Quinti, I., additional
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- 2022
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4. HIGH PHENOTYPIC VARIABILITY IN THREE SIBLINGS WITH ADA2 DEFICIENCY.
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Sculco, E., Paciaroni, K., Sangiorgi, E., Quinti, I., and Pulvirenti, F.
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- 2023
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5. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations
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Tim Niehues, Catherine Waruiru, Conleth Feighery, Uwe Schauer, Virginie Courteille, Kai Lehmberg, Ingo Müller, I. Esteves, Henner Morbach, Michael Borte, Patrick Hundsdoerfer, Klaus Schwarz, Ewelina Gowin, Alessandro Aiuti, Andreas Holbro, Federica Barzaghi, João Farela Neves, Dagmar Graf, Hannah Tamary, Veneta Milenova, Benedikt Boetticher, Eleonora Gambineri, Vera Goda, Alia Eldash, Jan-Christian Wasmuth, Fabio Candotti, Svetlana O. Sharapova, Markus Metzler, Juergen Brunner, Anna Hilfanova, Brindusa Ruxandra Capilna, Pere Soler-Palacín, Arnau Antolí, Horst von Bernuth, Vassilios Lougaris, Maria Carrabba, Bernd H. Belohradsky, Julian Thalhammer, Nathalie de Vergnes, Peter Olbrich, Peter Kopač, Leif G. Hanitsch, Alexandra Nieters, Filomeen Haerynck, Juliana Gabzdilova, Sezin Aydemir, Rabab El Hawary, Patrick F.K. Yong, Maria Giovanna Danieli, Alberto Tommasini, Sandra Steinmann, Ulrich Baumann, Figen Dogu, Elisabeth Förster-Waldl, Carolina Marasco, Donato Amodio, Lorenzo Lodi, Xavier Solanich, Caterina Cancrini, Brigita Sitkauskiene, Torsten Witte, Clementina Vanessa, Nima Rezaei, Jean-Christophe Goffard, Kirsten Wittke, Emmanouil Liatsis, Helen Baxendale, Susana L. Silva, Bodo Grimbacher, Henrike Ritterbusch, Evangelia Farmaki, Safa Meshaal, Sujal Ghosh, Larysa Kostyuchenko, David Edgar, Simone Cesaro, R Zeuner, Nerea Salmón Rodríguez, Isabella Quinti, Stephan Ehl, Pauline Brosselin, Joerg C. Henes, Pilar Llobet Agulló, Rosa Maria Dellepiane, Andrea Meinhardt, Marina Kojić, Georgios Sogkas, Stephan Borte, Catharina Schuetz, Suheyla Ocak, Karin Marschall, Lukas M. Gasteiger, Stefan Raffac, Sofia Tantou, Sadia Noorani, Matthaios Speletas, Philippe Randrianomenjanahary, Ursula Holzer, Ayca Kiykim, Johannes G. Liese, Angelo Vacca, Gisela Fecker, Ekrem Unal, Koen J. van Aerde, Alba Parra-Martínez, Kaan Boztug, Sophie Stiehler, Sybille Landwehr-Kenzel, Claudio Pignata, Jennifer Neubert, Janine Reichenbach, Shahnaz Parvin, Sarah Goddard, Andrea Schroll, Dirk Holzinger, Asghar Aghamohammadi, Hassan Abolhassani, Johannes Trück, Estela Paz-Artal, Shereen M. Reda, Anna Shcherbina, Maria Raptaki, Jaroslava Orosova, Beata Wolska-Kuśnierz, Tessa Kerre, Gerrit Ahrenstorf, Ben Zion Garty, Dirk Foell, Benjamin Becker, Ulrike F. Demel, Androniki Kapousouzi, Abraham Rutgers, Klaus Warnatz, Gemma Rocamora Blanch, Stephan Rusch, Luis M. Allende, Dalia Abd Elaziz, Safa Baris, Jorisvan Montfrans, Dominik T. Schneider, Raphael Scheible, Juana Gil-Herrera, Gerhard Kindle, Annarosa Soresina, Giovanna Fabio, Uwe Wintergerst, Emilia Faria, Maria Fasshauer, Silvia Ricci, Aisha Elmarsafy, Barbara Pietrucha, Carsten Speckmann, Nizar Mahlaoui, Ulrich Heininger, Isabelle Meyts, Matthew Buckland, Efimia Papadopoulou-Alataki, Robin Kobbe, A Herwadkar, Sebastian F. N. Bode, Ali Sobh, László Maródi, Baldassarre Martire, Chiara Azzari, Maximilian Heeg, Katja Masjosthusmann, Michael H. Albert, Matteo Chinello, Juan Luis Santos-Pérez, Aarnoud Huissoon, Tanya I. Coulter, Hendrik Schulze-Koops, Norbert Graf, Radwa Alkady, Jolanta Bernatoniene, Seraina Prader, Alenka Gagro, Joachim Roesler, Taco W. Kuijpers, Ewa Więsik-Szewczyk, Maria Elena Maccari, Conrad Ferdinand Lippert, Miriam González-Amores, Johannes Dirks, Daniel E Pleguezuelo, Christof M. Kramm, Anders Fasth, Volker Schuster, Olov Ekwall, Nikolaus Rieber, Javier Carbone, Petra Kaiser-Labusch, Diana Ernst, Lucia Augusta Baselli, Luis Ignacio Gonzalez-Granado, Maria Kanariou, Stefanie S. V. Henriet, Sigune Goldacker, Kerstin Felgentreff, Oana Joean, Fine Roosens, Fabian Hauck, Eva C. Schwaneck, Milos Jesenak, Manfred Hoenig, Lenka Kapustova, Christoph Boesecke, Alain Fischer, Sara Pereira da Silva, Julia Körholz, Ansgar Schulz, Carolynne Schwarze-Zander, Mikko Seppänen, Nermeen Galal, Nora Naumann-Bartsch, Tomaz Garcez, Peter Ciznar, Klara M. Posfay-Barbe, Zelimir Pavle Eric, Reinhold E. Schmidt, Hermann J. Girschick, Sabine Heine, Anika-Kerstin Biegner, Annick A. J. M. van de Ven, Stefan Schreiber, J. Merlijn van den Berg, Nurit Assia Batzir, Alexandra Jablonka, Kim Stol, Gregor Dückers, Antonios G.A. Kolios, Ioannis Kakkas, Christian Klemann, Marina N. Guseva, Sofia Grigoriadou, Elif Karakoc-Aydiner, Antonio Marzollo, Peter D. Arkwright, Urs C. Steiner, Sara Sebnem Kilic, Romina Dieli-Crimi, Gergely Kriván, Monika Sparber-Sauer, Marco Cazzaniga, Fulvio Porta, Paraskevi Maggina, Tomas Milota, Robbert G. M. Bredius, Martine Pergent, Klaus Tenbrock, Jana Pachlopnik Schmid, Florentia Dimitriou, Cathal Laurence Steele, Helen Bourne, Anna Bobcakova, Gerd Horneff, Judith Potjewijd, Marc Schmalzing, Tobias Ankermann, Paul Ryan, Oksana Boyarchuk, Necil Kutukculer, Carl Friedrich Classen, Zita Chovancová, Moira Thomas, Cinzia Milito, Michaela Bitzenhofer-Grüber, Faranaz Atschekzei, Eva Hlaváčková, Viviana Moschese, Julie Smet, Hans-Hartmut Peter, Carla Teixeira, Sabine M El-Helou, Suzanne de Kruijf Bazen, Helmut Wittkowski, Donate Jakoby, Marina Garcia-Prat, Esther de Vries, Richard Herriot, Sven Kracker, Alessandro Plebani, Lisa Göschl, Laura Hora Marques, Anna Sediva, Jiri Litzman, Mark M. Gompels, Renate Krüger, Şefika İlknur Kökçü Karadağ, Nadine Binder, Anna Szaflarska, Peter Jandus, Lisa Ibberson, Johann Greil, Ulf Schulze-Sturm, Mehtap Sirin, Aydan Ikinciogullari, Edyta Heropolitańska-Pliszka, Michael E. Weiss, Alla Skapenko, Lukas Wisgrill, Hana Alachkar, Uta Behrends, Silvia Sánchez-Ramón, Maria N. Hatzistilianou, Otilia Petrovicova, Darko Richter, Zoreh Nademi, Jürgen K. Rockstroh, Sohilla Lotfy, Markus G. Seidel, Timothy Ronan Leahy, Audra Blažienė, Translational Immunology Groningen (TRIGR), Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Inflammatory diseases, ARD - Amsterdam Reproduction and Development, University of Zurich, Ehl, Stephan, Thalhammer, J., Kindle, G., Nieters, A., Rusch, S., Seppanen, M. R. J., Fischer, A., Grimbacher, B., Edgar, D., Buckland, M., Mahlaoui, N., Ehl, S., Boztug, K., Brunner, J., Demel, U. F., Forster-Waldl, E., Gasteiger, L. M., Goschl, L., Kojic, M., Schroll, A., Seidel, M. G., Wintergerst, U., Wisgrill, L., Sharapova, S. O., Goffard, J. -C., Kerre, T., Meyts, I., Roosens, F., Smet, J., Haerynck, F., Eric, Z. P., Milenova, V., Gagro, A., Richter, D., Chovancova, Z., Hlavackova, E., Litzman, J., Milota, T., Sediva, A., Elaziz, D. A., Alkady, R. S., El Sayed El Hawary, R., Eldash, A. S., Galal, N., Lotfy, S., Meshaal, S. S., Reda, S. M., Sobh, A., Elmarsafy, A., Brosselin, P., Courteille, V., De Vergnes, N., Kracker, S., Pergent, M., Randrianomenjanahary, P., Ahrenstorf, G., Albert, M. H., Ankermann, T., Atschekzei, F., Baumann, U., Becker, B. C., Behrends, U., Belohradsky, B. H., Biegner, A. -K., Binder, N., Bode, S. F. N., Boesecke, C., Boetticher, B., Borte, M., Borte, S., Classen, C. F., Dirks, J., Duckers, G., El-Helou, S., Ernst, D., Fasshauer, M., Fecker, G., Felgentreff, K., Foell, D., Ghosh, S., Girschick, H. J., Goldacker, S., Graf, N., Graf, D., Greil, J., Hanitsch, L. G., Hauck, F., Heeg, M., Heine, S. I., Henes, J. C., Hoenig, M., Holzer, U., Holzinger, D., Horneff, G., Hundsdoerfer, P., Jablonka, A., Jakoby, D., Joean, O., Kaiser-Labusch, P., Klemann, C., Kobbe, R., Korholz, J., Kramm, C. M., Kruger, R., Landwehr-Kenzel, S., Lehmberg, K., Liese, J. G., Lippert, C. F., Maccari, M. E., Masjosthusmann, K., Meinhardt, A., Metzler, M., Morbach, H., Muller, I., Naumann-Bartsch, N., Neubert, J., Niehues, T., Peter, H. -H., Rieber, N., Ritterbusch, H., Rockstroh, J. K., Roesler, J., Schauer, U., Scheible, R., Schmalzing, M., Schmidt, R. E., Schneider, D. T., Schreiber, S., Schuetz, C., Schulz, A., Schulze-Koops, H., Schulze-Sturm, U., Schuster, V., Schwaneck, E. C., Schwarz, K., Schwarze-Zander, C., Sirin, M., Skapenko, A., Sogkas, G., Sparber-Sauer, M., Speckmann, C., Steinmann, S., Stiehler, S., Tenbrock, K., von Bernuth, H., Warnatz, K., Wasmuth, J. -C., Weiss, M., Witte, T., Wittke, K., Wittkowski, H., Zeuner, R. A., Farmaki, E., Hatzistilianou, M. N., Kakkas, I., Kanariou, M. G., Kapousouzi, A., Liatsis, E., Maggina, P., Papadopoulou-Alataki, E., Raptaki, M., Speletas, M., Tantou, S., Goda, V., Krivan, G., Marodi, L., Abolhassani, H., Aghamohammadi, A., Rezaei, N., Feighery, C., Leahy, T. R., Ryan, P., Batzir, N. A., Garty, B. Z., Tamary, H., Aiuti, A., Amodio, D., Azzari, C., Barzaghi, F., Baselli, L. A., Cancrini, C., Carrabba, M., Cazzaniga, M., Cesaro, S., Chinello, M., Danieli, M. G., Dellepiane, R. M., Fabio, G., Gambineri, E., Lodi, L., Lougaris, V., Marasco, C., Martire, B., Marzollo, A., Milito, C., Moschese, V., Pignata, C., Plebani, A., Porta, F., Quinti, I., Ricci, S., Soresina, A., Tommasini, A., Vacca, A., Vanessa, C., Blaziene, A., Sitkauskiene, B., Gowin, E., Heropolitanska-Pliszka, E., Pietrucha, B., Szaflarska, A., Wiesik-Szewczyk, E., Wolska-Kusnierz, B., Esteves, I., Faria, E., Marques, L. H., Neves, J. F., Silva, S. L., Teixeira, C., Pereira da Silva, S., Capilna, B. R., Guseva, M. N., Shcherbina, A., Bobcakova, A., Ciznar, P., Gabzdilova, J., Jesenak, M., Kapustova, L., Orosova, J., Petrovicova, O., Raffac, S., Kopac, P., Allende, L. M., Antoli, A., Blanch, G. R., Carbone, J., Dieli-Crimi, R., Garcia-Prat, M., Gil-Herrera, J., Gonzalez-Granado, L. I., Agullo, P. L., Olbrich, P., Parra-Martinez, A., Paz-Artal, E., Pleguezuelo, D. E., Rodriguez, N. S., Sanchez-Ramon, S., Santos-Perez, J. L., Solanich, X., Soler-Palacin, P., Gonzalez-Amores, M., Ekwall, O., Fasth, A., Bitzenhofer-Gruber, M., Candotti, F., Dimitriou, F., Heininger, U., Holbro, A., Jandus, P., Kolios, A. G. A., Marschall, K., Schmid, J. P., Posfay-Barbe, K. M., Prader, S., Reichenbach, J., Steiner, U. C., Truck, J., Bredius, R. G., de Kruijf- Bazen, S., de Vries, E., Henriet, S. S. V., Kuijpers, T. W., Potjewijd, J., Rutgers, A., Stol, K., van Aerde, K. J., Van den Berg, J. M., van de Ven, A. A. J. M., Montfrans, J., Aydemir, S., Baris, S., Dogu, F., Ikinciogullari, A., Karakoc-Aydiner, E., Kilic, S. S., Kiykim, A., Kokcu Karadag, S. I., Kutukculer, N., Ocak, S., Unal, E., Boyarchuk, O., Hilfanova, A., Kostyuchenko, L. V., Alachkar, H., Arkwright, P. D., Baxendale, H. E., Bernatoniene, J., Coulter, T. I., Garcez, T., Goddard, S., Gompels, M. M., Grigoriadou, S., Herriot, R., Herwadkar, A., Huissoon, A., Ibberson, L., Nademi, Z., Noorani, S., Parvin, S., Steele, C. L., Thomas, M., Waruiru, C., Yong, P. F. K., and Bourne, H.
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0301 basic medicine ,Male ,Pediatrics ,syndromic ,Sex Factor ,Disease ,registry ,medicine.disease_cause ,Cohort Studies ,0302 clinical medicine ,Primary Immunodeficiency Disease ,inborn error of immunity ,Immunology and Allergy ,warning signs ,Age Factor ,Registries ,Family history ,presenting symptom ,Child ,Primary immunodeficiency ,Granuloma ,autoimmune ,immune dysregulation ,inflammatory ,Adult ,Autoimmune Diseases ,Female ,Humans ,Infections ,Lymphoproliferative Disorders ,Middle Aged ,Primary Immunodeficiency Diseases ,Sex Factors ,Age Factors ,10177 Dermatology Clinic ,Infections/epidemiology ,3. Good health ,Settore MED/02 ,Warning signs ,Lymphoproliferative Disorder ,2723 Immunology and Allergy ,Infection ,Human ,medicine.medical_specialty ,Immunology ,610 Medicine & health ,Malignancy ,primary immunodeficiency ,Autoimmune Disease ,03 medical and health sciences ,Immunity ,Autoimmune Diseases/epidemiology ,medicine ,2403 Immunology ,business.industry ,warning sign ,Common variable immunodeficiency ,Granuloma/epidemiology ,Immune dysregulation ,medicine.disease ,Primary Immunodeficiency Diseases/epidemiology ,030104 developmental biology ,Lymphoproliferative Disorders/epidemiology ,Cohort Studie ,business ,030215 immunology - Abstract
BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.
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- 2021
6. Progressive Depletion of B and T Lymphocytes in Patients with Ataxia Telangiectasia: Results of the Italian Primary Immunodeficiency Network
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Emilia Cirillo, Agata Polizzi, Annarosa Soresina, Rosaria Prencipe, Giuliana Giardino, Caterina Cancrini, Andrea Finocchi, Beatrice Rivalta, Rosa M. Dellepiane, Lucia A. Baselli, Davide Montin, Antonino Trizzino, Rita Consolini, Chiara Azzari, Silvia Ricci, Lorenzo Lodi, Isabella Quinti, Cinzia Milito, Lucia Leonardi, Marzia Duse, Maria Carrabba, Giovanna Fabio, Patrizia Bertolini, Paola Coccia, Irene D’Alba, Andrea Pession, Francesca Conti, Marco Zecca, Claudio Lunardi, Manuela Lo Bianco, Santiago Presti, Laura Sciuto, Roberto Micheli, Dario Bruzzese, Vassilios Lougaris, Raffaele Badolato, Alessandro Plebani, Luciana Chessa, Claudio Pignata, Cirillo, E., Polizzi, A., Soresina, A., Prencipe, R., Giardino, G., Cancrini, C., Finocchi, A., Rivalta, B., Dellepiane, R. M., Baselli, L. A., Montin, D., Trizzino, A., Consolini, R., Azzari, C., Ricci, S., Lodi, L., Quinti, I., Milito, C., Leonardi, L., Duse, M., Carrabba, M., Fabio, G., Bertolini, P., Coccia, P., D'Alba, I., Pession, A., Conti, F., Zecca, M., Lunardi, C., Bianco, M. L., Presti, S., Sciuto, L., Micheli, R., Bruzzese, D., Lougaris, V., Badolato, R., Plebani, A., Chessa, L., and Pignata, C.
- Subjects
B lymphocyte ,T-Lymphocytes ,genotype ,Immunology ,T lymphocytes ,Ataxia Telangiectasia Mutated Proteins ,lymphopenia ,primary immunodeficiency ,Settore MED/02 ,Mutation ,Humans ,Ataxia telangiectasia ,B lymphocytes ,Immunology and Allergy ,Retrospective Studies - Abstract
Ataxia telangiectasia (AT) is a rare neurodegenerative genetic disorder due to bi-allelic mutations in the Ataxia Telangiectasia Mutated (ATM) gene. The aim of this paper is to better define the immunological profile over time, the clinical immune-related manifestations at diagnosis and during follow-up, and to attempt a genotype–phenotype correlation of an Italian cohort of AT patients. Retrospective data of 69 AT patients diagnosed between December 1984 and November 2019 were collected from the database of the Italian Primary Immunodeficiency Network. Patients were classified at diagnosis as lymphopenic (Group A) or non-lymphopenic (Group B). Fifty eight out of 69 AT patients (84%) were genetically characterized and distinguished according to the type of mutations in truncating/truncating (TT; 27 patients), non-truncating (NT)/T (28 patients), and NT/NT (5 patients). In 3 patients, only one mutation was detected. Data on age at onset and at diagnosis, cellular and humoral compartment at diagnosis and follow-up, infectious diseases, signs of immune dysregulation, cancer, and survival were analyzed and compared to the genotype. Lymphopenia at diagnosis was related per se to earlier age at onset. Progressive reduction of cellular compartment occurred during the follow-up with a gradual reduction of T and B cell number. Most patients of Group A carried bi-allelic truncating mutations, had a more severe B cell lymphopenia, and a reduced life expectancy. A trend to higher frequency of interstitial lung disease, immune dysregulation, and malignancy was noted in Group B patients. Lymphopenia at the onset and the T/T genotype are associated with a worst clinical course. Several mechanisms may underlie the premature and progressive immune decline in AT subjects.
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- 2022
7. Changes in health-related quality of life in common variable immunodeficiency: an eight-year journey, including the COVID-19 pandemic.
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Pulvirenti F, Villa A, D'Ambrosi M, Cusa G, Quijada-Morales P, de la Fuente-Munoz E, Sciannamea M, Garzi G, and Quinti I
- Abstract
Background: Personalized medicine requires the assessment of the impact of health care interventions on Health-Related Quality of Life., Research Design and Methods: We run an observational study of HRQoL in 140 CVID patients with biannual assessments over 8 years using a disease-specific tool, the CVID_QoL, and the GHQ questionnaires. Factors influencing changes in HRQoL scores were identified using multiple linear regression models with a stepwise procedure., Results: Infections frequency, female gender, and chronic enteropathy were associated with worse global CVID_QoL scores. The presence of permanent organ damage and older age contributed to the perception of being at risk of health deterioration, while chronic enteropathy was associated with fatigue. The presence of permanent organ damage was also associated with perceived difficulties in usual activities. The frequency of infections was the main risk factor for difficulties in long-term planning and perceptions of vulnerability. Before COVID-19, improved HRQoL scores were associated with reduced respiratory infections and changes in immunoglobulin replacement route and setting. The COVID-19 pandemic caused a sudden deterioration in all HRQoL dimensions, and a further deterioration in the emotional dimension was observed during the pandemic period. Patients who died during the study had worse CVID_QoL scores at all time points, confirming that HRQoL performance is strongly related to patient outcome., Conclusions: Periodic HRQoL assessments are needed to capture relevant issues that change over time in patients affected by long-term chronic conditions such CVID, possibly identifying areas of intervention.
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- 2024
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8. Charting a course for global progress in PIDs by 2030 - proceedings from the IPOPI global multi-stakeholders' summit (September 2023).
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Van Coillie S, Prévot J, Sánchez-Ramón S, Lowe DM, Borg M, Autran B, Segundo G, Pecoraro A, Garcelon N, Boersma C, Silva SL, Drabwell J, Quinti I, Meyts I, Ali A, Burns SO, van Hagen M, Pergent M, and Mahlaoui N
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- Humans, Stakeholder Participation, Global Health
- Abstract
The International Patient Organisation for Primary Immunodeficiencies (IPOPI) held its second Global Multi-Stakeholders' Summit, an annual stimulating and forward-thinking meeting uniting experts to anticipate pivotal upcoming challenges and opportunities in the field of primary immunodeficiency (PID). The 2023 summit focused on three key identified discussion points: (i) How can immunoglobulin (Ig) therapy meet future personalized patient needs? (ii) Pandemic preparedness: what's next for public health and potential challenges for the PID community? (iii) Diagnosing PIDs in 2030: what needs to happen to diagnose better and to diagnose more? Clinician-Scientists, patient representatives and other stakeholders explored avenues to improve Ig therapy through mechanistic insights and tailored Ig preparations/products according to patient-specific needs and local exposure to infectious agents, amongst others. Urgency for pandemic preparedness was discussed, as was the threat of shortage of antibiotics and increasing antimicrobial resistance, emphasizing the need for representation of PID patients and other vulnerable populations throughout crisis and care management. Discussion also covered the complexities of PID diagnosis, addressing issues such as global diagnostic disparities, the integration of patient-reported outcome measures, and the potential of artificial intelligence to increase PID diagnosis rates and to enhance diagnostic precision. These proceedings outline the outcomes and recommendations arising from the 2023 IPOPI Global Multi-Stakeholders' Summit, offering valuable insights to inform future strategies in PID management and care. Integral to this initiative is its role in fostering collaborative efforts among stakeholders to prepare for the multiple challenges facing the global PID community., Competing Interests: This study received funding from CSL Behring, Grifols and Takeda. The funder had the following involvement with the study: Company representatives contributed to the stakeholder discussions and reviewed the manuscript. All authors declare no other competing interests. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Van Coillie, Prévot, Sánchez-Ramón, Lowe, Borg, Autran, Segundo, Pecoraro, Garcelon, Boersma, Silva, Drabwell, Quinti, Meyts, Ali, Burns, van Hagen, Pergent and Mahlaoui.)
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- 2024
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9. Oropharyngeal microbial ecosystem perturbations influence the risk for acute respiratory infections in common variable immunodeficiency.
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Pulvirenti F, Giufrè M, Pentimalli TM, Camilli R, Milito C, Villa A, Sculco E, Cerquetti M, Pantosti A, and Quinti I
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- Humans, Male, Female, Middle Aged, Adult, Microbiota, Prospective Studies, Aged, RNA, Ribosomal, 16S genetics, Acute Disease, Bacteria classification, Bacteria genetics, Case-Control Studies, Common Variable Immunodeficiency microbiology, Common Variable Immunodeficiency immunology, Common Variable Immunodeficiency complications, Oropharynx microbiology, Respiratory Tract Infections microbiology, Respiratory Tract Infections immunology, Dysbiosis
- Abstract
Background: The respiratory tract microbiome is essential for human health and well-being and is determined by genetic, lifestyle, and environmental factors. Patients with Common Variable Immunodeficiency (CVID) suffer from respiratory and intestinal tract infections, leading to chronic diseases and increased mortality rates. While CVID patients' gut microbiota have been analyzed, data on the respiratory microbiome ecosystem are limited., Objective: This study aims to analyze the bacterial composition of the oropharynx of adults with CVID and its link with clinical and immunological features and risk for respiratory acute infections., Methods: Oropharyngeal samples from 72 CVID adults and 26 controls were collected in a 12-month prospective study. The samples were analyzed by metagenomic bacterial 16S ribosomal RNA sequencing and processed using the Quantitative Insights Into Microbial Ecology (QIME) pipeline. Differentially abundant species were identified and used to build a dysbiosis index. A machine learning model trained on microbial abundance data was used to test the power of microbiome alterations to distinguish between healthy individuals and CVID patients., Results: Compared to controls, the oropharyngeal microbiome of CVID patients showed lower alpha- and beta-diversity, with a relatively increased abundance of the order Lactobacillales , including the family Streptococcaceae . Intra-CVID analysis identified age >45 years, COPD, lack of IgA, and low residual IgM as associated with a reduced alpha diversity. Expansion of Haemophilus and Streptococcus genera was observed in patients with undetectable IgA and COPD, independent from recent antibiotic use. Patients receiving azithromycin as antibiotic prophylaxis had a higher dysbiosis score. Expansion of Haemophilus and Anoxybacillus was associated with acute respiratory infections within six months., Conclusions: CVID patients showed a perturbed oropharynx microbiota enriched with potentially pathogenic bacteria and decreased protective species. Low residual levels of IgA/IgM, chronic lung damage, anti antibiotic prophylaxis contributed to respiratory dysbiosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pulvirenti, Giufrè, Pentimalli, Camilli, Milito, Villa, Sculco, Cerquetti, Pantosti and Quinti.)
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- 2024
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10. Editorial: IgA and mucosal immunity in vaccinology and in protection from infection.
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Carsetti R and Quinti I
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- Humans, Vaccinology methods, Vaccines immunology, Animals, Vaccination, Immunity, Mucosal, Immunoglobulin A immunology
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2024
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11. Dysregulation of Toll-Like Receptor Signaling-Associated Gene Expression in X-Linked Agammaglobulinemia: Implications for Correlations Genotype-Phenotype and Disease Expression.
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Teocchi M, de Andrade Eugênio T, Furlaneto Marega L, Quinti I, and Dos Santos Vilela MM
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- Humans, Male, Adolescent, Child, Gene Expression Regulation, Adult, Child, Preschool, Young Adult, Female, Mutation, Agammaglobulinemia genetics, Agammaglobulinemia immunology, Genetic Diseases, X-Linked genetics, Genetic Diseases, X-Linked immunology, Agammaglobulinaemia Tyrosine Kinase genetics, Signal Transduction genetics, Genetic Association Studies, Toll-Like Receptors genetics, Toll-Like Receptors metabolism
- Abstract
Introduction: In X-linked agammaglobulinemia (XLA), the diversity of BTK variants complicates the study of genotype-phenotype correlations. Since BTK negatively regulates toll-like receptors (TLRs), we investigated if distinct BTK mutation types selectively modulate TLR pathways, affecting disease expression., Methods: Using reverse transcription-quantitative polymerase chain reaction, we quantified ten TLR signaling-related genes in XLA patients with missense (n = 3) and nonsense (n = 5) BTK mutations and healthy controls (n = 17)., Results: BTK, IRAK2, PIK3R4, REL, TFRC, and UBE2N were predominantly downregulated, while RIPK2, TLR3, TLR10, and TLR6 showed variable regulation. The missense XLA group exhibited significant downregulation of IRAK2, PIK3R4, REL, and TFRC and upregulation of TLR3 and/or TLR6., Conclusion: Hypo-expression of TLR3, TLR6, and TLR10 may increase susceptibility to infections, while hyper-expression might contribute to chronic inflammatory conditions like arthritis or inflammatory bowel disease. Our findings shed light on the important inflammatory component characteristic of some XLA patients, even under optimal therapeutic conditions., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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12. Editorial to the Special Issue "Clinical Immunology in Italy, with Special Emphasis to Primary and Acquired Immunodeficiencies: A Commemorative Issue in Honor of Prof. Fernando Aiuti".
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Aiuti A, D'Amelio R, Quinti I, and Rossi P
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Fernando Aiuti (Figure 1), born in Urbino on 8 June 1935, suddenly died on 9 January 2019, leaving a great void not only among his family members and those who knew him and appreciated his great humanity and acute intelligence, but in the entire immunological scientific community [...].
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- 2023
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13. Reply to Özdemir, Ö. Allergic Disease with Selective IgA Deficiency. Comment on "Cinicola et al. The Allergic Phenotype of Children and Adolescents with Selective IgA Deficiency: A Longitudinal Monocentric Study. J. Clin. Med. 2022, 11 , 5705".
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Cinicola BL, Brindisi G, Capponi M, Gori A, Loffredo L, De Castro G, Anania C, Spalice A, Guido CA, Milito C, Duse M, Quinti I, Pulvirenti F, and Zicari AM
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We carefully read the correspondence [...].
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- 2023
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14. SARS-CoV-2 pre-exposure prophylaxis with tixagevimab/cilgavimab (AZD7442) provides protection in inborn errors of immunity with antibody defects: a real-world experience.
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Pulvirenti F, Garzi G, Milito C, Sculco E, Sciannamea M, Napoli A, Cinti L, Roberto P, Punziano A, Carrabba M, Piano Mortari E, Carsetti R, Antonelli G, and Quinti I
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- Humans, SARS-CoV-2, Prospective Studies, Antibodies, Monoclonal, Antibodies, Viral, Immunoglobulin G, Pre-Exposure Prophylaxis, COVID-19
- Abstract
Background: Preventive strategies against severe COVID-19 in Inborn Errors of Immunity (IEI) include bivalent vaccines, treatment with SARS-CoV-2 monoclonal antibodies (mAbs), early antiviral therapies, and pre-exposure prophylaxis (PrEP)., Objective: To assess the effectiveness of the PrEP with tixagevimab/cilgavimab (AZD7442) in IEI with primary antibody defects during the COVID-19 Omicron wave., Methods: A six-month prospective study evaluated the SARS-CoV-2 infection rate and the COVID-19 severity in the AZD7442 group, in the no-AZD7442 group, and in a group of patients with a recent SARS-CoV-2 infection (< three months). Spike-specific IgG levels were measured at regular intervals., Results: Six out of thirty-three patients (18%) and 54/170 patients (32%) became infected in the AZD7442 group and in the no-AZD7442 group, respectively. Within 90 days post-administration, the AZD7442 group was 85% less likely to be infected and 82% less likely to have a symptomatic disease than the no-AZD7442 group. This effect was lost thereafter. In the entire cohort, no mortality/hospitalisation was observed. The control group of 35 recently infected patients was 88% and 92% less likely to be infected than the AZD7442 and no-AZD7442 groups. Serum anti-Spike IgG reached the highest peak seven days post-AZD7442 PrEP then decreased, remaining over 1000 BAU/mL 180 days thereafter., Conclusion: In patients with IEI and antibody defects, AZD7442 prophylaxis had a transient protective effect, possibly lost possibly because of the appearance of new variants. However, PrEP with newer mAbs might still represent a feasible preventive strategy in the future in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pulvirenti, Garzi, Milito, Sculco, Sciannamea, Napoli, Cinti, Roberto, Punziano, Carrabba, Piano Mortari, Carsetti, Antonelli and Quinti.)
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- 2023
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15. Decline of gastric cancer mortality in common variable immunodeficiency in the years 2018-2022.
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Milito C, Pulvirenti F, Garzi G, Sculco E, Cinetto F, Firinu D, Lagnese G, Punziano A, Discardi C, Costanzo G, Felice C, Spadaro G, Ferrari S, and Quinti I
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- Adult, Humans, Prospective Studies, Pandemics, Gastroscopy adverse effects, Stomach Neoplasms pathology, Helicobacter Infections complications, Helicobacter Infections epidemiology, Helicobacter Infections diagnosis, Common Variable Immunodeficiency epidemiology, Common Variable Immunodeficiency complications, Helicobacter pylori, Precancerous Conditions pathology
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Introduction: In patients with Common Variable Immunodeficiency, malignancy has been reported as the leading cause of death in adults, with a high risk of B-cell lymphomas and gastric cancer., Methods: We conducted a five-year prospective study aiming to update the incidence and mortality of gastric cancer and the incidence of gastric precancerous lesions in 512 CVID patients who underwent a total of 400 upper gastrointestinal endoscopies., Results: In the pre-pandemic period, 0.58 endoscopies were performed per patient/year and in the COVID-19 period, 0.39 endoscopies were performed per patient/year. Histology revealed areas with precancerous lesions in about a third of patients. Patients who had more than one gastroscopy during the study period were more likely to have precancerous lesions. Two patients received a diagnosis of gastric cancer in the absence of Helicobacter pylori infection. The overall prevalence of Helicobacter pylori infection in biopsy specimens was 19.8% and related only to active gastritis. Among patients who had repeated gastroscopies, about 20% progressed to precancerous lesions, mostly independent of Helicobacter pylori., Discussion: While gastric cancer accounted for one in five deaths from CVID in our previous survey, no gastric cancer deaths were recorded in the past five years, likely consistent with the decline in stomach cancer mortality observed in the general population. However, during the COVID-19 pandemic, cancer screening has been delayed. Whether such a delay or true decline could be the reason for the lack of gastric cancer detection seen in CVID may become clear in the coming years. Due to the high incidence of precancerous lesions, we cannot rely on observed and predicted trends in gastric cancer mortality and strongly recommend tailored surveillance programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Milito, Pulvirenti, Garzi, Sculco, Cinetto, Firinu, Lagnese, Punziano, Discardi, Costanzo, Felice, Spadaro, Ferrari and Quinti.)
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- 2023
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16. Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations.
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Friman V, Quinti I, Davydov AN, Shugay M, Farroni C, Engström E, Pour Akaber S, Barresi S, Mohamed A, Pulvirenti F, Milito C, Granata G, Giorda E, Ahlström S, Karlsson J, Marasco E, Marcellini V, Bocci C, Cascioli S, Scarsella M, Phad G, Tilevik A, Tartaglia M, Bemark M, Chudakov DM, Carsetti R, and Grimsholm O
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- Humans, B-Lymphocytes, Germinal Center, Precursor Cells, B-Lymphoid, Autoimmunity, Common Variable Immunodeficiency genetics
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Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27
bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally, functionally, T cell-dependent activation showed that naive B cells in CVID patients are badly equipped for activation and induction of mismatch repair genes. We conclude that central tolerance is functional whereas peripheral selection is defective in CVID patients with autoimmune manifestations, which could underpin the development of autoimmunity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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17. Functional CVIDs phenotype clusters identified by the integration of immune parameters after BNT162b2 boosters.
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Piano Mortari E, Pulvirenti F, Marcellini V, Terreri S, Salinas AF, Ferrari S, Di Napoli G, Guadagnolo D, Sculco E, Albano C, Guercio M, Di Cecca S, Milito C, Garzi G, Pesce AM, Bonanni L, Sinibaldi M, Bordoni V, Di Cecilia S, Accordini S, Castilletti C, Agrati C, Quintarelli C, Zaffina S, Locatelli F, Carsetti R, and Quinti I
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- Humans, BNT162 Vaccine, Longitudinal Studies, SARS-CoV-2, Antibodies, Neutralizing, Phenotype, COVID-19, Common Variable Immunodeficiency
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Introduction: Assessing the response to vaccinations is one of the diagnostic criteria for Common Variable Immune Deficiencies (CVIDs). Vaccination against SARS-CoV-2 offered the unique opportunity to analyze the immune response to a novel antigen. We identify four CVIDs phenotype clusters by the integration of immune parameters after BTN162b2 boosters., Methods: We performed a longitudinal study on 47 CVIDs patients who received the 3rd and 4th vaccine dose of the BNT162b2 vaccine measuring the generation of immunological memory. We analyzed specific and neutralizing antibodies, spike-specific memory B cells, and functional T cells., Results: We found that, depending on the readout of vaccine efficacy, the frequency of responders changes. Although 63.8% of the patients have specific antibodies in the serum, only 30% have high-affinity specific memory B cells and generate recall responses., Discussion: Thanks to the integration of our data, we identified four functional groups of CVIDs patients with different B cell phenotypes, T cell functions, and clinical diseases. The presence of antibodies alone is not sufficient to demonstrate the establishment of immune memory and the measurement of the in-vivo response to vaccination distinguishes patients with different immunological defects and clinical diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Piano Mortari, Pulvirenti, Marcellini, Terreri, Salinas, Ferrari, Di Napoli, Guadagnolo, Sculco, Albano, Guercio, Di Cecca, Milito, Garzi, Pesce, Bonanni, Sinibaldi, Bordoni, Di Cecilia, Accordini, Castilletti, Agrati, Quintarelli, Zaffina, Locatelli, Carsetti and Quinti.)
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- 2023
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18. Case Report: Interindividual variability and possible role of heterozygous variants in a family with deficiency of adenosine deaminase 2: are all heterozygous born equals?
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Pulvirenti F, Cinicola BL, Ferrari S, Guadagnolo D, Sculco E, Capponi M, Loffredo L, Sciannamea M, Insalaco A, Quinti I, De Benedetti F, and Zicari AM
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- Male, Female, Adolescent, Humans, Child, Adult, Adenosine Deaminase genetics, Intercellular Signaling Peptides and Proteins, Agammaglobulinemia diagnosis, Agammaglobulinemia genetics, Agammaglobulinemia complications, Vasculitis etiology
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Deficiency of adenosine deaminase 2 (DADA2) is a rare systemic autoinflammatory disease, typically with autosomal recessive inheritance, usually caused by biallelic loss of function mutations in the ADA2 gene. The phenotypic spectrum is broad, generally including fever, early-onset vasculitis, stroke, and hematologic dysfunction. Heterozygous carriers may show related signs and symptoms, usually milder and at an older age. Here we describe the case of two relatives, the proband and his mother, bearing an ADA2 homozygous pathogenic variant, and a heterozygous son. The proband was a 17-year-old boy with intermittent fever, lymphadenopathies, and mild hypogammaglobulinemia. He also had sporadic episodes of aphthosis, livedo reticularis and abdominal pain. Hypogammaglobulinemia was documented when he was 10 years old, and symptoms appeared in his late adolescence. The mother demonstrated mild hypogammaglobulinemia, chronic pericarditis since she was 30 years old and two transient episodes of diplopia without lacunar lesions on MRI. ADA2 (NM_001282225.2) sequencing identified both mother and son as homozygous for the c.1358A>G, p.(Tyr453Cys) variant. ADA2 activity in the proband and the mother was 80-fold lower than in the controls. Clinical features in both patients improved on anti-tumor necrosis factor therapy. An older son was found to be heterozygous for the same mutation post-mortem. He died at the age of 12 years due to a clinical picture of fever, lymphadenitis, skin rash and hypogammaglobulinemia evolving toward fatal multiorgan failure. Biopsies of skin, lymph nodes, and bone marrow excluded lymphomas and vasculitis. Despite being suspected of symptomatic carrier, the contribution of an additional variant in compound heterozygosity, or further genetic could not be ruled out, due to poor quality of DNA samples available. In conclusion, this familiar case demonstrated the wide range of phenotypic variability in DADA2. The search for ADA2 mutations and the assessment of ADA2 activity should be considered also in patients with the association of hypogammaglobulinemia and inflammatory conditions, also with late presentation and in absence of vasculitis. Furthermore, the clinical picture of the deceased carrier suggests a possible contribution of heterozygous pathogenic variants to inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pulvirenti, Cinicola, Ferrari, Guadagnolo, Sculco, Capponi, Loffredo, Sciannamea, Insalaco, Quinti, De Benedetti and Zicari.)
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- 2023
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19. Long term longitudinal follow-up of an AD-HIES cohort: the impact of early diagnosis and enrollment to IPINet centers on the natural history of Job's syndrome.
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Carrabba M, Dellepiane RM, Cortesi M, Baselli LA, Soresina A, Cirillo E, Giardino G, Conti F, Dotta L, Finocchi A, Cancrini C, Milito C, Pacillo L, Cinicola BL, Cossu F, Consolini R, Montin D, Quinti I, Pession A, Fabio G, Pignata C, Pietrogrande MC, and Badolato R
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Job's syndrome, or autosomal dominant hyperimmunoglobulin E syndrome (AD-HIES, STAT3-Dominant Negative), is a rare inborn error of immunity (IEI) with multi-organ involvement and long-life post-infective damage. Longitudinal registries are of primary importance in improving our knowledge of the natural history and management of these rare disorders. This study aimed to describe the natural history of 30 Italian patients with AD-HIES recorded in the Italian network for primary immunodeficiency (IPINet) registry. This study shows the incidence of manifestations present at the time of diagnosis versus those that arose during follow up at a referral center for IEI. The mean time of diagnostic delay was 13.7 years, while the age of disease onset was < 12 months in 66.7% of patients. Respiratory complications, namely bronchiectasis and pneumatoceles, were present at diagnosis in 46.7% and 43.3% of patients, respectively. Antimicrobial prophylaxis resulted in a decrease in the incidence of pneumonia from 76.7% to 46.7%. At the time of diagnosis, skin involvement was present in 93.3% of the patients, including eczema (80.8%) and abscesses (66.7%). At the time of follow-up, under therapy, the prevalence of complications decreased: eczema and skin abscesses reduced to 63.3% and 56.7%, respectively. Antifungal prophylaxis decreased the incidence of mucocutaneous candidiasis from 70% to 56.7%. During the SARS-CoV-2 pandemic, seven patients developed COVID-19. Survival analyses showed that 27 out of 30 patients survived, while three patients died at ages of 28, 39, and 46 years as a consequence of lung bleeding, lymphoma, and sepsis, respectively. Analysis of a cumulative follow-up period of 278.7 patient-years showed that early diagnosis, adequate management at expertise centers for IEI, prophylactic antibiotics, and antifungal therapy improve outcomes and can positively influence the life expectancy of patients., (© 2023. The Author(s).)
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- 2023
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20. A beacon in the dark: COVID-19 course in CVID patients from two European countries: Different approaches, similar outcomes.
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Milito C, Firinu D, Bez P, Villa A, Punziano A, Lagnese G, Costanzo G, van Leeuwen LPM, Piazza B, Deiana CM, d'Ippolito G, Del Giacco SR, Rattazzi M, Spadaro G, Quinti I, Scarpa R, Dalm VASH, and Cinetto F
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- Humans, Prospective Studies, Retrospective Studies, SARS-CoV-2, Antibodies, Monoclonal, Antibodies, Viral, Antiviral Agents, COVID-19 epidemiology
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Background: CVID patients present an increased risk of prolonged SARS-CoV-2 infection and re-infection and a higher COVID-19-related morbidity and mortality compared to the general population. Since 2021, different therapeutic and prophylactic strategies have been employed in vulnerable groups (vaccination, SARS-CoV-2 monoclonal antibodies and antivirals). The impact of treatments over the last 2 years has not been explored in international studies considering the emergence of viral variants and different management between countries., Methods: A multicenter retrospective/prospective real-life study comparing the prevalence and outcomes of SARS-CoV-2 infection between a CVID cohort from four Italian Centers (IT-C) and one cohort from the Netherlands (NL-C), recruiting 773 patients., Results: 329 of 773 CVID patients were found positive for SARS-CoV-2 infection between March 1
st , 2020 and September 1st 2022. The proportion of CVID patients infected was comparable in both national sub-cohorts. During all waves, chronic lung disease, "complicated" phenotype, chronic immunosuppressive treatment and cardiovascular comorbidities impacted on hospitalization, whereas risk factors for mortality were older age, chronic lung disease, and bacterial superinfections. IT-C patients were significantly more often treated, both with antivirals and mAbs, than NL-C patients. Outpatient treatment, available only in Italy, started from the Delta wave. Despite this, no significant difference was found for COVID-19 severity between the two cohorts. However, pooling together specific SARS-CoV-2 outpatient treatments (mAbs and antivirals), we found a significant effect on the risk of hospitalization starting from Delta wave. Vaccination with ≥ 3 doses shortened RT-PCR positivity, with an additional effect only in patients receiving antivirals., Conclusions: The two sub-cohorts had similar COVID-19 outcomes despite different treatment approaches. This points out that specific treatment should now be reserved for selected subgroups of CVID patients, based on pre-existing conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Milito, Firinu, Bez, Villa, Punziano, Lagnese, Costanzo, van Leeuwen, Piazza, Deiana, d’Ippolito, Del Giacco, Rattazzi, Spadaro, Quinti, Scarpa, Dalm and Cinetto.)- Published
- 2023
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21. Safety of mRNA COVID-19 Vaccines in Patients with Inborn Errors of Immunity: an Italian Multicentric Study.
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Milito C, Cinetto F, Garzi G, Palladino A, Puca M, Brambilla E, De Vitis C, Costanzo G, Scarpa R, Punziano A, Lagnese G, Del Giacco S, Spadaro G, Quinti I, and Firinu D
- Subjects
- Aged, Humans, Middle Aged, RNA, Messenger, Vaccination adverse effects, Anaphylaxis etiology, COVID-19 prevention & control, COVID-19 Vaccines adverse effects
- Abstract
Purpose: Little is known about vaccine safety in inborn errors of immunity (IEI) patients during the current vaccination campaign for COVID-19. To better investigate the reactogenicity and adverse event profile after two, three, and four doses of mRNA vaccines, we conducted an observational, multicentric study on 342 PID patients from four Italian Referral Centres., Methods: We conducted a survey on self-reported adverse reactions in IEI patients who received mRNA vaccine by administering a questionnaire after each dose., Results: Over the whole study period, none of the patients needed hospitalization or had hypersensitivity reactions, including anaphylaxis and delayed injection site reaction. After two vaccination doses, 35.4% of patients showed only local reactogenicity-related symptoms (RrS), 44.4% reported both systemic and local RrS, and 5% reported only systemic RrS. In more than 60% of cases, local or systemic RrS were mild. After the first and second booster doses, patients showed fewer adverse events (AEs) than after the first vaccination course. Patients aged 50 years and older reported adverse events and RrS less frequently. Among AEs requiring treatment, one common variable immune deficiency patient affected by T cell large granular lymphocytic leukemia developed neutropenia and one patient had Bell's paralysis perhaps during herpes zoster reactivation., Conclusion: Although our follow-up period is relatively short, the safety data we reported are reassuring. This data would help to contrast the vaccine hesitancy often manifested by patients with IEI and to better inform their healthcare providers., (© 2022. The Author(s).)
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- 2023
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22. COVID-19 Severity, Cardiological Outcome, and Immunogenicity of mRNA Vaccine on Adult Patients With 22q11.2 DS.
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Pulvirenti F, Mortari EP, Putotto C, Terreri S, Fernandez Salinas A, Cinicola BL, Cimini E, Di Napoli G, Sculco E, Milito C, Versacci P, Agrati C, Marino B, Carsetti R, and Quinti I
- Subjects
- Humans, Adult, BNT162 Vaccine, COVID-19 Vaccines, SARS-CoV-2, Vaccination, mRNA Vaccines, COVID-19 epidemiology, COVID-19 prevention & control, DiGeorge Syndrome, Lymphopenia
- Abstract
Background: The contemporaneous presence of immune defects and heart diseases in patients with 22q11.2 deletion syndrome (22q11.3DS) might represent risk factors for severe coronavirus 2019 disease (COVID-19)., Objective: To analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcome in 22q11.2DS patients and immunogenicity of different doses of mRNA SARS-CoV-2 vaccine., Methods: Longitudinal observational study on SARS-CoV-2 outcome in 60 adults with 22q11.2DS (March 2020-June 2022). Anti-Spike, and anti-receptor binding domain (RBD) antibody responses, generation of Spike-specific memory B cells (MBCs) and Spike-specific T cells at different time points before and after the mRNA BNT162b2 vaccination were evaluated in 16 22q11.2DS patients., Results: We recorded a 95% rate of vaccination, with almost all patients being immunized with the booster dose. Twenty-one patients had SARS-CoV-2 infection. Three patients were infected before vaccine availability, 6 after receiving 2 doses of vaccine, and 12 after one booster dose. The SARS-CoV-2- infection had a mild course, except in one unvaccinated patient with several comorbidities who died from acute respiratory distress syndrome (fatality rate 5%). Infected patients had more frequently moderate/severe intellectual disability, lymphopenia, and lower CD4+ count. Despite major congenital heart diseases, COVID-19 did not impact cardiological conditions. The BNT162b2 vaccine induced S1-immunoglobulin G (IgG) responses, low serum S1-IgA, and slightly impaired specific MBCs response. Specific T-cell responses observed were related to lymphocytes and CD4+ T cell counts., Conclusions: The SARS-CoV-2 infection had a mild course in most patients with 22q11.2DS, even in patients with major cardiovascular diseases. Immunization induced Spike-specific IgG responses and generated specific MBCs and memory T cells. The weaker memory responses in patients with lymphopenia suggested the need for additional doses., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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23. The BNT162b2 vaccine induces humoral and cellular immune memory to SARS-CoV-2 Wuhan strain and the Omicron variant in children 5 to 11 years of age.
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Cinicola BL, Piano Mortari E, Zicari AM, Agrati C, Bordoni V, Albano C, Fedele G, Schiavoni I, Leone P, Fiore S, Capponi M, Conti MG, Petrarca L, Stefanelli P, Spalice A, Midulla F, Palamara AT, Quinti I, Locatelli F, and Carsetti R
- Subjects
- Humans, Child, Child, Preschool, BNT162 Vaccine, SARS-CoV-2, Immunologic Memory, mRNA Vaccines, Antibodies, COVID-19 prevention & control, Vaccines
- Abstract
SARS-CoV-2 mRNA vaccines prevent severe COVID-19 by generating immune memory, comprising specific antibodies and memory B and T cells. Although children are at low risk of severe COVID-19, the spreading of highly transmissible variants has led to increasing in COVID-19 cases and hospitalizations also in the youngest, but vaccine coverage remains low. Immunogenicity to mRNA vaccines has not been extensively studied in children 5 to 11 years old. In particular, cellular immunity to the wild-type strain (Wuhan) and the cross-reactive response to the Omicron variant of concern has not been investigated. We assessed the humoral and cellular immune response to the SARS-CoV-2 BNT162b2 vaccine in 27 healthy children. We demonstrated that vaccination induced a potent humoral and cellular immune response in all vaccinees. By using spike-specific memory B cells as a measurable imprint of a previous infection, we found that 50% of the children had signs of a past, undiagnosed infection before vaccination. Children with pre-existent immune memory generated significantly increased levels of specific antibodies, and memory T and B cells, directed against not only the wild type virus but also the omicron variant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cinicola, Piano Mortari, Zicari, Agrati, Bordoni, Albano, Fedele, Schiavoni, Leone, Fiore, Capponi, Conti, Petrarca, Stefanelli, Spalice, Midulla, Palamara, Quinti, Locatelli and Carsetti.)
- Published
- 2022
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24. Age-dependent NK cell dysfunctions in severe COVID-19 patients.
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Fionda C, Ruggeri S, Sciumè G, Laffranchi M, Quinti I, Milito C, Palange P, Menichini I, Sozzani S, Frati L, Gismondi A, Santoni A, and Stabile H
- Subjects
- Humans, SARS-CoV-2, Killer Cells, Natural, Transforming Growth Factor beta, COVID-19, Skin Diseases
- Abstract
Natural Killer (NK) cells are key innate effectors of antiviral immune response, and their activity changes in ageing and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we investigated the age-related changes of NK cell phenotype and function during SARS-CoV-2 infection, by comparing adult and elderly patients both requiring mechanical ventilation. Adult patients had a reduced number of total NK cells, while elderly showed a peculiar skewing of NK cell subsets towards the CD56
low CD16high and CD56neg phenotypes, expressing activation markers and check-point inhibitory receptors. Although NK cell degranulation ability is significantly compromised in both cohorts, IFN-γ production is impaired only in adult patients in a TGF-β-dependent manner. This inhibitory effect was associated with a shorter hospitalization time of adult patients suggesting a role for TGF-β in preventing an excessive NK cell activation and systemic inflammation. Our data highlight an age-dependent role of NK cells in shaping SARS-CoV-2 infection toward a pathophysiological evolution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fionda, Ruggeri, Sciumè, Laffranchi, Quinti, Milito, Palange, Menichini, Sozzani, Frati, Gismondi, Santoni and Stabile.)- Published
- 2022
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25. The Allergic Phenotype of Children and Adolescents with Selective IgA Deficiency: A Longitudinal Monocentric Study.
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Cinicola BL, Brindisi G, Capponi M, Gori A, Loffredo L, De Castro G, Anania C, Spalice A, Guido CA, Milito C, Duse M, Quinti I, Pulvirenti F, and Zicari AM
- Abstract
Background: Selective IgA deficiency (SIgAD) is the most common inborn error of immunity. The exact prevalence and pathogenesis of allergy in SIgAD have not yet been defined. We aimed to describe the prevalence and the characteristics of allergy in pediatric SIgAD subjects, evaluate the association between allergy and other comorbidities, and define the immune phenotype of allergic and non-allergic patients., Methods: Clinical and immunological data from 67 SIgAD patients were collected over a 13-year period at a single center. Patients' characteristics were analyzed according to the presence of allergy., Results: Allergy was diagnosed in 34% of SIgAD patients, with a median age at allergy diagnosis of 8 years. Allergy was the second-most-common clinical manifestation, following recurrent respiratory infections. Among the allergic group, 74% had rhinitis, 30% asthma, 30% atopic dermatitis, and 22% food allergy; one out of three had more than one allergic manifestation. SIgAD patients showed more frequent transitory lymphopenia and a lower count of CD19+ at diagnosis than at last FU. However, compared to non-allergic subjects, allergic patients did not differ in their immune phenotype, number and severity of infections, or increased autoimmunity., Conclusions: In our longitudinal study, compared to non-allergic SIgAD patients, those with allergies did not present a more severe immune defect or complex clinical phenotype. However, evaluation and early identification of allergy in the context of SIgAD assessment, both at diagnosis and during FU, and definition of a proper management are important to prevent complications and improve the patient's quality of life.
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- 2022
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26. Real-life data on monoclonal antibodies and antiviral drugs in Italian inborn errors of immunity patients during COVID-19 pandemic.
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Garzi G, Cinetto F, Firinu D, Di Napoli G, Lagnese G, Punziano A, Bez P, Cinicola BL, Costanzo G, Scarpa R, Pulvirenti F, Rattazzi M, Spadaro G, Quinti I, and Milito C
- Subjects
- Antibodies, Monoclonal therapeutic use, Antiviral Agents therapeutic use, Humans, Pandemics, SARS-CoV-2, Antineoplastic Agents, Immunological, COVID-19 Drug Treatment
- Abstract
Background: Since the beginning of the COVID-19 pandemic, patients with Inborn Errors of Immunity have been infected by SARS-CoV-2 virus showing a spectrum of disease ranging from asymptomatic to severe COVID-19. A fair number of patients did not respond adequately to SARS-CoV-2 vaccinations, thus early therapeutic or prophylactic measures were needed to prevent severe or fatal course or COVID-19 and to reduce the burden of hospitalizations., Methods: Longitudinal, multicentric study on patients with Inborn Errors of Immunity immunized with mRNA vaccines treated with monoclonal antibodies and/or antiviral agents at the first infection and at reinfection by SARS-CoV-2. Analyses of efficacy were performed according to the different circulating SARS-CoV-2 strains., Results: The analysis of the cohort of 192 SARS-CoV-2 infected patients, across 26 months, showed the efficacy of antivirals on the risk of hospitalization, while mabs offered a positive effect on hospitalization, and COVID-19 severity. This protection was consistent across the alpha, delta and early omicron waves, although the emergence of BA.2 reduced the effect of available mabs. Hospitalized patients treated with mabs and antivirals had a lower risk of ICU admission. We reported 16 re-infections with a length of SARS-CoV-2 positivity at second infection shorter among patients treated with mabs. Treatment with antivirals and mabs was safe., Conclusions: The widespread use of specific therapy, vaccination and better access to care might have contributed to mitigate risk of mortality, hospital admission, and severe disease. However, the rapid spread of new viral strains underlines that mabs and antiviral beneficial effects should be re- evaluated over time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garzi, Cinetto, Firinu, Di Napoli, Lagnese, Punziano, Bez, Cinicola, Costanzo, Scarpa, Pulvirenti, Rattazzi, Spadaro, Quinti and Milito.)
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- 2022
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27. The Impact of SARS-CoV-2 Infection in Patients with Inborn Errors of Immunity: the Experience of the Italian Primary Immunodeficiencies Network (IPINet).
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Giardino G, Milito C, Lougaris V, Punziano A, Carrabba M, Cinetto F, Scarpa R, Dellepiane RM, Ricci S, Rivalta B, Conti F, Marzollo A, Firinu D, Cirillo E, Lagnese G, Cancrini C, Martire B, Danieli MG, Pession A, Vacca A, Azzari C, Fabio G, Soresina A, Agostini C, Spadaro G, Badolato R, Cicalese MP, Aiuti A, Plebani A, Quinti I, and Pignata C
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- Adult, Child, Female, Hospitalization, Humans, Male, Retrospective Studies, SARS-CoV-2, Post-Acute COVID-19 Syndrome, COVID-19 complications, COVID-19 epidemiology, Common Variable Immunodeficiency epidemiology
- Abstract
COVID-19 manifestations range from asymptomatic to life-threatening infections. The outcome in different inborn errors of immunity (IEI) is still a matter of debate. In this retrospective study, we describe the experience of the of the Italian Primary Immunodeficiencies Network (IPINet). Sixteen reference centers for adult or pediatric IEI were involved. One hundred fourteen patients were enrolled including 35 pediatric and 79 adult patients. Median age was 32 years, and male-to-female ratio was 1.5:1. The most common IEI were 22q11.2 deletion syndrome in children (26%) and common variable immunodeficiency (CVID) in adults (65%). Ninety-one patients did not require hospital admission, and among these, 33 were asymptomatic. Hospitalization rate was 20.17%. Older age (p 0.004) and chronic lung disease (p 0.0008) represented risk factors for hospitalization. Hospitalized patients mainly included adults suffering from humoral immunodeficiencies requiring immunoglobulin replacement therapy and as expected had lower B cell counts compared to non-hospitalized patients. Infection fatality rate in the whole cohort was 3.5%. Seroconversion was observed is 86.6% of the patients evaluated and in 83.3% of CVID patients. 16.85% of the patients reported long-lasting COVID symptoms. All but one patient with prolonged symptoms were under IgRT. The fatality rate observed in IEI was slightly similar to the general population. The age of the patients who did not survive was lower compared to the general population, and the age stratified mortality in the 50-60 age range considerable exceeded the mortality from 50 to 60 age group of the Italian population (14.3 vs 0.6%; p < 0.0001). We hypothesize that this is due to the fact that comorbidities in IEI patients are very common and usually appear early in life., (© 2022. The Author(s).)
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- 2022
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28. Allergic manifestations of inborn errors of immunity and their impact on the diagnosis: A worldwide study.
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El-Sayed ZA, El-Ghoneimy DH, Ortega-Martell JA, Radwan N, Aldave JC, Al-Herz W, Al-Nesf MA, Condino-Neto A, Cole T, Eley B, Erwa NHH, Espinosa-Padilla S, Faria E, Rosario Filho NA, Fuleihan R, Galal N, Garabedian E, Hintermeyer M, Imai K, Irani C, Kamal E, Kechout N, Klocperk A, Levin M, Milota T, Ouederni M, Paganelli R, Pignata C, Qamar FN, Quinti I, Qureshi S, Radhakrishnan N, Rezaei N, Routes J, Singh S, Siniah S, Abdel-Hakam Taha I, Tanno LK, Van Dort B, Volokha A, and Sullivan K
- Abstract
Background: Allergies have long been observed in Inborn Errors of Immunity (IEI) and might even be the first presentation resulting in delayed diagnosis or misdiagnosis in some cases. However, data on the prevalence of allergic diseases among IEI patients are limited and contradictory., Objective: To provide a worldwide view of allergic diseases, across a broad spectrum of IEI, and their impact on the timely diagnosis of IEI., Methods: This is a worldwide study, conceived by the World Allergy Organization (WAO) Inborn Errors of Immunity Committee. A questionnaire was developed and pilot-tested and was sent via email to collect data from 61 immunology centers known to treat pediatric and/or adult IEI patients in 41 countries. In addition, a query was submitted to The United States Immunodeficiency Network (USIDNET) at its website., Results: Thirty centers in 23 countries caring for a total 8450 IEI patients responded. The USIDNET dataset included 2332 patients. Data from responders showed that a median (IQR) of 16.3% (10-28.8%) of patients experienced allergic diseases during the course of their IEI as follows: 3.6% (1.3-11.3%) had bronchial asthma, 3.6% (1.9-9.1%) atopic dermatitis, 3.0% (1.0-7.8%) allergic rhinitis, and 1.3% (0.5-3.3%) food allergy. As per the USIDNET data, the frequency of allergy among IEI patients was 68.8% (bronchial asthma in 46.9%). The percentage of IEI patients who presented initially with allergic disorders was 8% (5-25%) and diagnosis delay was reported in 7.5% (0.9-20.6%). Predominantly antibody deficiencies had the highest frequency of allergic disease followed by combined immunodeficiency with a frequency of 40.3% (19.2-62.5%) and 20.0% (10-32%) respectively. As per the data of centers, anaphylaxis occurred in 25/8450 patients (0.3%) whereas per USIDNET dataset, it occurred in 249/2332 (10.6%); drugs and food allergy were the main causes in both datasets., Conclusions: This multinational study brings to focus the relation between allergic diseases and IEI. Major allergies do occur in IEI patients but were less frequent than the general population. Initial presentation with allergy could adversely affect the timely diagnosis of IEI. There is a need for policies to raise awareness and educate primary care and other referring specialties on the association of allergic diseases with IEI. This study provides a network among centers for future prospective studies in the field., Competing Interests: The authors declare that they have no competing interests., (© 2022 The Authors.)
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- 2022
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29. T-Cell Defects Associated to Lack of Spike-Specific Antibodies after BNT162b2 Full Immunization Followed by a Booster Dose in Patients with Common Variable Immune Deficiencies.
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Pulvirenti F, Di Cecca S, Sinibaldi M, Piano Mortari E, Terreri S, Albano C, Guercio M, Sculco E, Milito C, Ferrari S, Locatelli F, Quintarelli C, Carsetti R, and Quinti I
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- Antibodies, Viral, CD40 Ligand, Humans, Immunization, Immunoglobulin A, Immunoglobulin G, SARS-CoV-2, Tumor Necrosis Factor-alpha, Vaccines, Synthetic, mRNA Vaccines, BNT162 Vaccine, COVID-19 prevention & control
- Abstract
Following the third booster dose of the mRNA vaccine, Common Variable Immune Deficiencies (CVID) patients may not produce specific antibodies against the virus spike protein. The T-cell abnormalities associated with the absence of antibodies are still a matter of investigation. Spike-specific IgG and IgA, peripheral T cell subsets, CD40L and cytokine expression, and Spike-specific specific T-cells responses were evaluated in 47 CVID and 26 healthy donors after three doses of BNT162b2 vaccine. Testing was performed two weeks after the third vaccine dose. Thirty-six percent of the patients did not produce anti-SARS-CoV-2 IgG or IgA antibodies. Non responder patients had lower peripheral blood lymphocyte counts, circulating naïve and central memory T-cells, low CD40L expression on the CD4+CD45+RO+ and CD8+CD45+RO+ T-cells, high frequencies of TNFα and IFNγ expressing CD8+ T-cells, and defective release of IFNγ and TNFα following stimulation with Spike peptides. Non responders had a more complex disease phenotype, with higher frequencies of structural lung damage and autoimmunity, especially autoimmune cytopenia. Thirty-five percent of them developed a SARS-CoV-2 infection after immunization in comparison to twenty percent of CVID who responded to immunization with antibodies production. CVID-associated T cell abnormalities contributed to the absence of SARS-CoV-2 specific antibodies after full immunization.
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- 2022
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30. IgG Autoantibodies Against IgE from Atopic Dermatitis Can Induce the Release of Cytokines and Proinflammatory Mediators from Basophils and Mast Cells.
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Poto R, Quinti I, Marone G, Taglialatela M, de Paulis A, Casolaro V, and Varricchi G
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- Animals, Autoantibodies pharmacology, Cytokines pharmacology, Eicosanoids, Histamine, Humans, Immunoglobulin E, Immunoglobulin G pharmacology, Interleukin-13 pharmacology, Interleukin-4 pharmacology, Leukotriene C4, Mast Cells, Prostaglandins, Rabbits, Basophils, Dermatitis, Atopic
- Abstract
IgE-mediated release of proinflammatory mediators and cytokines from basophils and mast cells is a central event in allergic disorders. Several groups of investigators have demonstrated the presence of autoantibodies against IgE and/or FcεRI in patients with chronic spontaneous urticaria. By contrast, the prevalence and functional activity of anti-IgE autoantibodies in atopic dermatitis (AD) are largely unknown. We evaluated the ability of IgG anti-IgE from patients with AD to induce the in vitro IgE-dependent activation of human basophils and skin and lung mast cells. Different preparations of IgG anti-IgE purified from patients with AD and rabbit IgG anti-IgE were compared for their triggering effects on the in vitro release of histamine and type 2 cytokines (IL-4, IL-13) from basophils and of histamine and lipid mediators (prostaglandin D
2 and cysteinyl leukotriene C4 ) from human skin and lung mast cells. One preparation of human IgG anti-IgE out of six patients with AD induced histamine release from basophils, skin and lung mast cells. This preparation of human IgG anti-IgE induced the secretion of cytokines and eicosanoids from basophils and mast cells, respectively. Human monoclonal IgE was a competitive antagonist of both human and rabbit IgG anti-IgE. Human anti-IgE was more potent than rabbit anti-IgE for IL-4 and IL-13 production by basophils and histamine, prostaglandin D2 and leukotriene C4 release from mast cells. Functional anti-IgE autoantibodies rarely occur in patients with AD. When present, they induce the release of proinflammatory mediators and cytokines from basophils and mast cells, thereby possibly contributing to sustained IgE-dependent inflammation in at least a subset of patients with this disorder., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Poto, Quinti, Marone, Taglialatela, de Paulis, Casolaro and Varricchi.)- Published
- 2022
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31. Progressive Depletion of B and T Lymphocytes in Patients with Ataxia Telangiectasia: Results of the Italian Primary Immunodeficiency Network.
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Cirillo E, Polizzi A, Soresina A, Prencipe R, Giardino G, Cancrini C, Finocchi A, Rivalta B, Dellepiane RM, Baselli LA, Montin D, Trizzino A, Consolini R, Azzari C, Ricci S, Lodi L, Quinti I, Milito C, Leonardi L, Duse M, Carrabba M, Fabio G, Bertolini P, Coccia P, D'Alba I, Pession A, Conti F, Zecca M, Lunardi C, Bianco ML, Presti S, Sciuto L, Micheli R, Bruzzese D, Lougaris V, Badolato R, Plebani A, Chessa L, and Pignata C
- Subjects
- Ataxia Telangiectasia Mutated Proteins genetics, Humans, Mutation genetics, Retrospective Studies, T-Lymphocytes, Ataxia Telangiectasia diagnosis, Ataxia Telangiectasia genetics, Lymphopenia
- Abstract
Ataxia telangiectasia (AT) is a rare neurodegenerative genetic disorder due to bi-allelic mutations in the Ataxia Telangiectasia Mutated (ATM) gene. The aim of this paper is to better define the immunological profile over time, the clinical immune-related manifestations at diagnosis and during follow-up, and to attempt a genotype-phenotype correlation of an Italian cohort of AT patients. Retrospective data of 69 AT patients diagnosed between December 1984 and November 2019 were collected from the database of the Italian Primary Immunodeficiency Network. Patients were classified at diagnosis as lymphopenic (Group A) or non-lymphopenic (Group B). Fifty eight out of 69 AT patients (84%) were genetically characterized and distinguished according to the type of mutations in truncating/truncating (TT; 27 patients), non-truncating (NT)/T (28 patients), and NT/NT (5 patients). In 3 patients, only one mutation was detected. Data on age at onset and at diagnosis, cellular and humoral compartment at diagnosis and follow-up, infectious diseases, signs of immune dysregulation, cancer, and survival were analyzed and compared to the genotype. Lymphopenia at diagnosis was related per se to earlier age at onset. Progressive reduction of cellular compartment occurred during the follow-up with a gradual reduction of T and B cell number. Most patients of Group A carried bi-allelic truncating mutations, had a more severe B cell lymphopenia, and a reduced life expectancy. A trend to higher frequency of interstitial lung disease, immune dysregulation, and malignancy was noted in Group B patients. Lymphopenia at the onset and the T/T genotype are associated with a worst clinical course. Several mechanisms may underlie the premature and progressive immune decline in AT subjects., (© 2022. The Author(s).)
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- 2022
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32. Mortality in Severe Antibody Deficiencies Patients during the First Two Years of the COVID-19 Pandemic: Vaccination and Monoclonal Antibodies Efficacy.
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Milito C, Cinetto F, Palladino A, Garzi G, Punziano A, Lagnese G, Scarpa R, Rattazzi M, Pesce AM, Pulvirenti F, Di Napoli G, Spadaro G, Carsetti R, and Quinti I
- Abstract
Patients with severely impaired antibody responses represent a group at-risk in the SARS-CoV-2 pandemic due to the lack of Spike-specific neutralizing antibodies. The main objective of this paper was to assess, by a longitudinal prospective study, COVID-19 infection and mortality rates, and disease severity in the first two years of the pandemic in a cohort of 471 Primary Antibody Defects adult patients. As secondary endpoints, we compared SARS-CoV-2 annual mortality rate to that observed over a 10-year follow-up in the same cohort, and we assessed the impact of interventions done in the second year, vaccination and anti-SARS-CoV-2 monoclonal antibodies administration on the disease outcome. Forty-one and 84 patients were infected during the first and the second year, respectively. Despite a higher infection and reinfection rate, and a higher COVID-19-related mortality rate compared to the Italian population, the pandemic did not modify the annual mortality rate for any cause in our cohort compared to that registered over the last ten years in the same cohort. PADs patients who died from COVID-19 had an underlying end-stage lung disease. We showed a beneficial effect of MoAbs administration on the likelihood of hospitalization and development of severe disease. In conclusion, COVID-19 did not cause excess mortality in Severe Antibody Deficiencies.
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- 2022
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33. Severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Combination Therapy in Patients With Coronavirus Disease 2019 and Primary Antibody Deficiency.
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Pulvirenti F, Milito C, Cinetto F, Fernandez Salinas A, Terreri S, Piano Mortari E, Auria S, Soccodato V, Miriam L, Nicastri E, Vincenzi L, Carsetti R, D'Offizi G, and Quinti I
- Subjects
- Antibodies, Monoclonal immunology, Antibodies, Monoclonal therapeutic use, Antibodies, Viral immunology, Antineoplastic Agents, Immunological, Humans, Prospective Studies, Real-Time Polymerase Chain Reaction, Standard of Care, Antibodies, Viral therapeutic use, Common Variable Immunodeficiency, Primary Immunodeficiency Diseases drug therapy, SARS-CoV-2 isolation & purification, COVID-19 Drug Treatment
- Abstract
Background: Previous reports highlighted the efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs) against coronavirus disease 2019., Methods: We conducted a prospective study on the clinical outcome and antiviral effects of mAbs added to standard of care therapy in SARS-CoV-2-infected patients with primary antibody defects., Results: Median time of SARS-CoV-2 quantitative polymerase chain reaction (qPCR) positivity was shorter in 8 patients treated with mAbs (22 days) than in 10 patients treated with standard of care therapy only (37 days, P=.026). Median time of SARS-CoV-2 qPCR positivity from mAb administration was 10 days., Conclusions: The SARS-CoV-2 mAbs treatment was effective and well tolerated in patients with primary antibody defects., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)
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- 2022
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34. Case Series: Convalescent Plasma Therapy for Patients with COVID-19 and Primary Antibody Deficiency.
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Lang-Meli J, Fuchs J, Mathé P, Ho HE, Kern L, Jaki L, Rusignuolo G, Mertins S, Somogyi V, Neumann-Haefelin C, Trinkmann F, Müller M, Thimme R, Umhau M, Quinti I, Wagner D, Panning M, Cunningham-Rundles C, Laubner K, and Warnatz K
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- Adolescent, Adult, Aged, Antibodies, Monoclonal immunology, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Child, Female, Humans, Immunization, Passive methods, Male, Middle Aged, Virus Shedding immunology, Young Adult, COVID-19 Serotherapy, COVID-19 immunology, COVID-19 therapy, Plasma immunology, Primary Immunodeficiency Diseases immunology, SARS-CoV-2 immunology
- Abstract
Patients with primary antibody deficiency are at risk for severe and in many cases for prolonged COVID-19. Convalescent plasma treatment of immunocompromised individuals could be an option especially in countries with limited access to monoclonal antibody therapies. While studies in immunocompetent COVID19 patients have demonstrated only a limited benefit, evidence for the safety, timing, and effectiveness of this treatment in antibody-deficient patients is lacking. Here, we describe 16 cases with primary antibody deficiency treated with convalescent plasma in four medical centers. In our cohort, treatment was associated with a reduction in viral load and improvement of clinical symptoms, even when applied over a week after onset of infection. There were no relevant side effects besides a short-term fever reaction in one patient. Longitudinal full-genome sequencing revealed the emergence of mutations in the viral genome, potentially conferring an antibody escape in one patient with persistent viral RNA shedding upon plasma treatment. However, he resolved the infection after a second course of plasma treatment. Thus, our data suggest a therapeutic benefit of convalescent plasma treatment in patients with primary antibody deficiency even months after infection. While it appears to be safe, PCR follow-up for SARS-CoV-2 is advisable and early re-treatment might be considered in patients with persistent viral shedding., (© 2021. The Author(s).)
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- 2022
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35. The Immune Response to SARS-CoV-2 Vaccination: Insights Learned From Adult Patients With Common Variable Immune Deficiency.
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Quinti I, Locatelli F, and Carsetti R
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- Adult, COVID-19 complications, Common Variable Immunodeficiency complications, Female, Humans, Immunogenicity, Vaccine, Immunologic Memory, Male, Spike Glycoprotein, Coronavirus immunology, Vaccination, Antibodies, Monoclonal immunology, Antibodies, Viral immunology, B-Lymphocyte Subsets immunology, COVID-19 immunology, COVID-19 Vaccines immunology, Common Variable Immunodeficiency immunology, SARS-CoV-2 physiology
- Abstract
CVID patients have an increased susceptibility to vaccine-preventable infections. The question on the potential benefits of immunization of CVID patients against SARS-CoV-2 offered the possibility to analyze the defective mechanisms of immune responses to a novel antigen. In CVID, as in immunocompetent subjects, the role of B and T cells is different between infected and vaccinated individuals. Upon vaccination, variable anti-Spike IgG responses have been found in different CVID cohorts. Immunization with two doses of mRNA vaccine did not generate Spike-specific classical memory B cells (MBCs) but atypical memory B cells (ATM) with low binding capacity to Spike protein. Spike-specific T-cells responses were also induced in CVID patients with a variable frequency, differently from specific T cells produced after multiple exposures to viral antigens following influenza virus immunization and infection. The immune response elicited by SARS-CoV-2 infection was enhanced by subsequent immunization underlying the need to immunize convalescent COVID-19 CVID patients after recovery. In particular, immunization after SARS-Cov-2 infection generated Spike-specific classical memory B cells (MBCs) with low binding capacity to Spike protein and Spike-specific antibodies in a high percentage of CVID patients. The search for a strategy to elicit an adequate immune response post-vaccination in CVID patients is necessary. Since reinfection with SARS-CoV-2 has been documented, at present SARS-CoV-2 positive CVID patients might benefit from new preventing strategy based on administration of anti-SARS-CoV-2 monoclonal antibodies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Quinti, Locatelli and Carsetti.)
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- 2022
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36. Impaired memory B-cell response to the Pfizer-BioNTech COVID-19 vaccine in patients with common variable immunodeficiency.
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Fernandez Salinas A, Piano Mortari E, Terreri S, Milito C, Zaffina S, Perno CF, Locatelli F, Quinti I, and Carsetti R
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- BNT162 Vaccine, COVID-19 Vaccines, Humans, SARS-CoV-2, COVID-19, Common Variable Immunodeficiency
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- 2022
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37. Cellular Immunology and COVID-19.
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Quinti I
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- Humans, Periodicals as Topic, COVID-19 immunology, Immunity, Cellular, SARS-CoV-2 immunology
- Abstract
In "Cellular Immunology and COVID-19" (a Special Issue of Cells ), a panel of leading scientists provides an exhaustive overview of the different aspects of the immune mechanisms underlying COVID-19 [...].
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- 2021
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38. Granulomatous-lymphocytic interstitial lung disease: an international research prioritisation.
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Hurst JR, Abbas SH, Bintalib HM, Alfaro TM, Baumann U, Burns SO, Condliffe A, Davidsen JR, Fevang B, Gennery AR, Haerynck F, Jacob J, Jolles S, Lamers O, Bergeron A, Malphettes M, Meignin V, Milito C, Milota T, Pergent M, Prasse A, Quinti I, Renzoni E, Sediva A, Stolz D, Smits B, Strauss F, van de Ven AAJM, van Montfrans J, and Warnatz K
- Abstract
The first ever research prioritisation exercise in GLILD: this survey identified areas of interest in the diagnosis, treatment and management of GLILD, which can be used as a roadmap for future research https://bit.ly/3nVuzti., Competing Interests: Provenance: Submitted article, peer reviewed.Conflict of interest: J.R. Hurst reports grants, personal fees and nonfinancial support from pharmaceutical companies that make medicines to treat respiratory and immunological diseases outside the submitted work. Conflict of interest: S.M. Abbas has nothing to disclose. Conflict of interest: H.M. Bintalib has nothing to disclose. Conflict of interest: T.M. Alfaro has nothing to disclose. Conflict of interest: U. Baumann has nothing to disclose. Conflict of interest: S.O. Burns reports personal fees from CSL Behring, Baxalta US Inc., Biotest, the European Union, the National Institute of Health Research, UCLH and GOSH/Institute of Child Health Biomedical Research Centers, and CSL Behring, outside the submitted work. Conflict of interest: A. Condliffe has nothing to disclose. Conflict of interest: J.R. Davidsen has nothing to disclose. Conflict of interest: B. Fevang has nothing to disclose. Conflict of interest: A.R. Gennery has nothing to disclose. Conflict of interest: F. Haerynck has nothing to disclose. Conflict of interest: J. Jacob reports personal fees from Boehringer Ingelheim, Roche and GlaxoSmithKline, outside the submitted work. Conflict of interest: S. Jolles has nothing to disclose. Conflict of interest: O. Lamers has nothing to disclose. Conflict of interest: A. Bergeron reports grants from SOS Oxygene, personal fees from Takeda, and personal fees from AstraZeneca, Pfizer, MSD, Gilead and Enanta, outside the submitted work. Conflict of interest: M. Malphettes has nothing to disclose. Conflict of interest: V. Meignin has nothing to disclose. Conflict of interest: C. Milito has nothing to disclose. Conflict of interest: T. Milota has nothing to disclose. Conflict of interest: M. Pergent has nothing to disclose. Conflict of interest: A. Prasse reports personal fees from Boehringer Ingelheim, Roche, Novartis, Chiesi, Pliant and AstraZeneca outside the submitted work. Conflict of interest: I. Quinti has nothing to disclose. Conflict of interest: E. Renzoni reports grants from Boehringer Ingelheim, and lecture fees from Boehringer Ingelheim and Roche, outside the submitted work. Conflict of interest: A. Sediva has nothing to disclose. Conflict of interest: D. Stolz reports grants from AstraZeneca AG, Curetis AG and Boston Scientific, and payment for lectures and/or advisory boards from AstraZeneca AG, Novartis AG, GSK AG, Roche AG, Zambon, Pfizer, Schwabe Pharma AG, Vifor AG, Chiesi AG and MSD, outside the submitted work. Conflict of interest: B. Smits has nothing to disclose. Conflict of interest: F. Strauss has nothing to disclose. Conflict of interest: A.A.J.M. van de Ven has nothing to disclose. Conflict of interest: J. van Montfrans reports having participated in an advisory board for Takeda during the conduct of the study. Conflict of interest: K. Warnatz reports grants from Bristol Myers Squibb outside the submitted work., (Copyright ©The authors 2021.)
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- 2021
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39. Medical algorithm: Diagnosis and management of antibody immunodeficiencies.
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Šedivá A, Milota T, Litzman J, Quinti I, Meyts I, Burns S, and Jolles S
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- Algorithms, Antibodies, Humans, Immunologic Deficiency Syndromes diagnosis, Immunologic Deficiency Syndromes therapy
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- 2021
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40. COVID-19 in complex common variable immunodeficiency patients affected by lung diseases.
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Milito C, Soccodato V, Auria S, Pulvirenti F, and Quinti I
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- Age Factors, Bronchiectasis immunology, COVID-19 immunology, COVID-19 virology, Chronic Disease epidemiology, Common Variable Immunodeficiency immunology, Disease Susceptibility, Humans, Lung Diseases, Interstitial immunology, Risk Factors, SARS-CoV-2 immunology, SARS-CoV-2 isolation & purification, Bronchiectasis epidemiology, COVID-19 diagnosis, Common Variable Immunodeficiency complications, Lung Diseases, Interstitial epidemiology, Severity of Illness Index
- Abstract
Purpose of Review: In the general population, the risk of severe COVID-19 is associated with old age, male sex, hypertension, obesity and chronic diseases. Chronic lung diseases are listed as additional risk factors for hospitalization and ICU admission. The purpose of this review is to define whether chronic lung diseases, such as bronchiectasis and interstitial diseases, represent a risk for a severe SARS-CoV-2 infection in patients affected by common variable immunodeficiency (CVID), the most common symptomatic primary antibody defect., Recent Findings: CVID patients with SARS-CoV-2 infection have been reported since the beginning of the pandemic with a wide range of clinical presentations ranging from asymptomatic to mild/moderate and severe COVID-19. The meta-analysis of 88 CVID cases described in large cohorts and case reports demonstrated that CVID patients with chronic lung involvement have an increased risk for severe COVID-19 in comparison to CVID without lung diseases (50 vs. 28%, relative risk 1.75, 95% confidence interval 1.04--2.92, P = 0.043). Differently from the general population, age and metabolic comorbidities did not represent a risk factor for severe course in this patient's population., Summary: Underlying chronic lung diseases but not age represent a risk factor for severe COVID-19 in CVID. Prompt therapeutic intervention should be adopted in SARS-CoV-2 positive CVID patients with chronic lung diseases independently of their age., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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41. Poking COVID-19: Insights on Genomic Constraints among Immune-Related Genes between Qatari and Italian Populations.
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Mbarek H, Cocca M, Al-Sarraj Y, Saad C, Mezzavilla M, AlMuftah W, Cocciadiferro D, Novelli A, Quinti I, AlTawashi A, Salvaggio S, AlThani A, Novelli G, and Ismail SI
- Subjects
- Adult, Alleles, COVID-19 epidemiology, Communicable Disease Control, Disease Susceptibility metabolism, Exome genetics, Female, Gene Frequency genetics, Genetic Predisposition to Disease epidemiology, Genetics, Population, Genomics methods, Humans, Immunity, Innate immunology, Italy epidemiology, Male, Qatar epidemiology, SARS-CoV-2 genetics, SARS-CoV-2 pathogenicity, Exome Sequencing methods, Whole Genome Sequencing methods, COVID-19 genetics, Genetic Predisposition to Disease genetics, Host Microbial Interactions genetics
- Abstract
Host genomic information, specifically genomic variations, may characterize susceptibility to disease and identify people with a higher risk of harm, leading to better targeting of care and vaccination. Italy was the epicentre for the spread of COVID-19 in Europe, the first country to go into a national lockdown and has one of the highest COVID-19 associated mortality rates. Qatar, on the other hand has a very low mortality rate. In this study, we compared whole-genome sequencing data of 14398 adults and Qatari-national to 925 Italian individuals. We also included in the comparison whole-exome sequence data from 189 Italian laboratory-confirmed COVID-19 cases. We focused our study on a curated list of 3619 candidate genes involved in innate immunity and host-pathogen interaction. Two population-gene metric scores, the Delta Singleton-Cohort variant score (DSC) and Sum Singleton-Cohort variant score (SSC), were applied to estimate the presence of selective constraints in the Qatari population and in the Italian cohorts. Results based on DSC and SSC metrics demonstrated a different selective pressure on three genes (MUC5AC, ABCA7, FLNA) between Qatari and Italian populations. This study highlighted the genetic differences between Qatari and Italian populations and identified a subset of genes involved in innate immunity and host-pathogen interaction.
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- 2021
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42. SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best.
- Author
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Salinas AF, Mortari EP, Terreri S, Quintarelli C, Pulvirenti F, Di Cecca S, Guercio M, Milito C, Bonanni L, Auria S, Romaggioli L, Cusano G, Albano C, Zaffina S, Perno CF, Spadaro G, Locatelli F, Carsetti R, and Quinti I
- Subjects
- Humans, Immunoglobulin G blood, Immunologic Memory, Lymphocytes immunology, Spike Glycoprotein, Coronavirus immunology, Antibodies, Viral blood, COVID-19 prevention & control, COVID-19 Vaccines immunology, Immunologic Deficiency Syndromes immunology, SARS-CoV-2 immunology
- Abstract
Background: Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization., Methods: Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine., Results: The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only., Conclusion: In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected., (© 2021. The Author(s).)
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- 2021
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43. B Cell Response Induced by SARS-CoV-2 Infection Is Boosted by the BNT162b2 Vaccine in Primary Antibody Deficiencies.
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Pulvirenti F, Fernandez Salinas A, Milito C, Terreri S, Piano Mortari E, Quintarelli C, Di Cecca S, Lagnese G, Punziano A, Guercio M, Bonanni L, Auria S, Villani F, Albano C, Locatelli F, Spadaro G, Carsetti R, and Quinti I
- Subjects
- Adult, Antibodies, Viral immunology, COVID-19 complications, COVID-19 prevention & control, Convalescence, Female, Humans, Immunization, Immunoglobulin G immunology, Male, Middle Aged, Primary Immunodeficiency Diseases complications, Spike Glycoprotein, Coronavirus immunology, T-Lymphocytes immunology, BNT162 Vaccine immunology, COVID-19 immunology, Memory B Cells immunology, Primary Immunodeficiency Diseases immunology, SARS-CoV-2 immunology
- Abstract
Background: Patients with primary antibody deficiencies are at risk in the current COVID-19 pandemic due to their impaired response to infection and vaccination. Specifically, patients with common variable immunodeficiency (CVID) generated poor spike-specific antibody and T cell responses after immunization., Methods: Thirty-four CVID convalescent patients after SARS-CoV-2 infection, 38 CVID patients immunized with two doses of the BNT162b2 vaccine, and 20 SARS-CoV-2 CVID convalescents later and immunized with BNT162b2 were analyzed for the anti-spike IgG production and the generation of spike-specific memory B cells and T cells., Results: Spike-specific IgG was induced more frequently after infection than after vaccination (82% vs. 34%). The antibody response was boosted in convalescents by vaccination. Although immunized patients generated atypical memory B cells possibly by extra-follicular or incomplete germinal center reactions, convalescents responded to infection by generating spike-specific memory B cells that were improved by the subsequent immunization. Poor spike-specific T cell responses were measured independently from the immunological challenge., Conclusions: SARS-CoV-2 infection primed a more efficient classical memory B cell response, whereas the BNT162b2 vaccine induced non-canonical B cell responses in CVID. Natural infection responses were boosted by subsequent immunization, suggesting the possibility to further stimulate the immune response by additional vaccine doses in CVID.
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- 2021
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44. Anti-COVID-19 Vaccination in Patients with Autoimmune-Autoinflammatory Disorders and Primary/Secondary Immunodeficiencies: The Position of the Task Force on Behalf of the Italian Immunological Societies.
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D'Amelio R, Asero R, Cassatella MA, Laganà B, Lunardi C, Migliorini P, Nisini R, Parronchi P, Quinti I, Racanelli V, Senna G, Vacca A, and Maggi E
- Abstract
The Coronavirus disease 2019 (COVID-19) pandemic has represented an unprecedented challenge for humankind from health, economic, and social viewpoints. In February 2020, Italy was the first western country to be deeply hit by the pandemic and suffered the highest case/fatality rate among western countries. Brand new anti-COVID-19 vaccines have been developed and made available in <1-year from the viral sequence publication. Patients with compromised immune systems, such as autoimmune-autoinflammatory disorders (AIAIDs), primary (PIDs) and secondary (SIDs) immunodeficiencies, have received careful attention for a long time regarding their capacity to safely respond to traditional vaccines. The Italian Immunological Societies, therefore, have promptly faced the issues of safety, immunogenicity, and efficacy/effectiveness of the innovative COVID-19 vaccines, as well as priority to vaccine access, in patients with AIADs, PIDs, and SIDs, by organizing an ad-hoc Task Force. Patients with AIADs, PIDs, and SIDs: (1) Do not present contraindications to COVID-19 vaccines if a mRNA vaccine is used and administered in a stabilized disease phase without active infection. (2) Should usually not discontinue immunosuppressive therapy, which may be modulated depending on the patient's clinical condition. (3) When eligible, should have a priority access to vaccination. In fact, immunizing these patients may have relevant social/health consequences, since these patients, if infected, may develop chronic infection, which prolongs viral spread and facilitates the emergence of viral variants.
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- 2021
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