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1. Inductive plasma thruster (IPT) for an atmosphere breathing electric propulsion system: Design and set in operation

Author

Francesco, Romano, Georg, Herdrich, Roberts, Peter C. E., Boxberger, A., Chan, Y. -A, Traub, C., Fasoulas, S., Smith, K., Edmondson, S., Haigh, S., Crisp, N., Abrao Oiko, V. T., Lyons, R., Worrall, S. D., Livadiotti, S., Huyton, C., Sinpetru, L., Outlaw, R., Becedas, J., Dominguez, R. M., González, D., Hanessian, V., Mølgaard, A., Nielsen, J., Bisgaard, M., Garcia-Almiñana, D., Rodriguez-Donaire, S., Sureda, M., Kataria, D., Villain, R., Santiago Perez, J., Conte, A., Belkouchi, B., Schwalber, A., Heißerer, B., mirko magarotto, and daniele pavarin

Published
2019

2. Modelling and Simulation of Very Low Earth Orbits

Author

GONZALEZ, D., CANAS, V., BECEDAS, J., DOMINGUEZ, R. M., ROBERTS, P. C. E., CRISP, N. H., OIKO, V. T. A., EDMONDSON, S., WORRALL, S. D., HAIGH, S., SMITH, K., LYONS, R. E., LIVADIOTTI, S., HUYTON, C., SINPETRU, L. A., RODRIGUEZ-DONAIRE, S., GARCIA-ALMINANA, D., NIETO, M., MUNOZ, C., SUREDA, M., KATARIA, D., HERDRICH, G. H., ROMANO, F., BINDER, T., BOXBERGER, A., FASOULAS, S., TRAUB, C., OUTLAW, R., GHIZONI, L., JUNGNELL, V., BAY, K., MORSBOL, J., VILLAIN, R., PEREZ, J. S., CONTE, A., BELKOUCHI, B., SCHWALBER, A., and HEIszERER, B.

Subjects
SIMULATION, AEROSPACE SYSTEMS, MODELLING, Astrophysics::Earth and Planetary Astrophysics, AERODYNAMICS, Physics::Atmospheric and Oceanic Physics
Abstract

Flying a satellite at very low earth orbit is a technological challenge. It presents advantages, such as increase resolution in optical payloads, reduce costs of launch and enhance the use of air breathing propulsion and specular materials. The density of the atmosphere at these altitudes is much higher, behaving as a free molecular flow. This has severe implications in the increase of drag torques and forces that has to be analyzed in depth. We analyze the effects and the perturbations to small satellites, affecting their dynamics, performance and lifetime by implementing and analyzing realistic models of the environment at VLEO.

Published
2019
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3. Clinical features and follow-up in patients with 22q11.2 deletion syndrome

Author

Cancrini, C, Puliafito, P, Digilio, M, Soresina, A, Martino, S, Rondelli, R, Consolini, R, Ruga, E, Cardinale, F, Finocchi, A, Romiti, Ml, Martire, B, Bacchetta, R, Albano, V, Carotti, A, Specchia, F, Montin, D, Cirillo, E, Cocchi, G, Trizzino, A, Bossi, G, Milanesi, O, Azzari, C, Corsello, G, Pignata, C, Aiuti, A, Pietrogrande, M, Marino, B, Ugazio, A, Plebani, A, Rossi, P, Pierani, P, Gabrielli, A, Danieli, M, De Mattia, D, Sisto, C, Dammacco, F, Ranieri, G, Pession, A, Ricci, G, Minelli, P, Lougaris, V, Badolato, R, Cattaneo, R, Airò, P, Mura, R, Cossu, F, Del Giacco, S, Manconi, P, Consarino, C, Dello Russo, A, Miniero, R, Anastasio, E, Marino, S, Russo, G, Paganelli, R, Sperlì, D, Carpino, L, Aricò, M, Gambineri, E, Lippi, F, Canessa, C, Maggi, E, Romagnani, S, Matucci, A, Vultaggio, A, Gattorno, M, Castagnola, E, Nigro, G, Presta, G, Civino, A, Buzi, F, Gambaretto, G, Fasoli, S, Salpietro, C, Gallizzi, R, Dellepiane, R, Panisi, C, Fabio, G, Carrabba, M, Roncarolo, M, Biondi, A, Vallinoto, C, Poggi, V, Menna, G, Di Nardo, R, Sottile, R, Marone, G, Spadaro, G, Carli, M, Basso, G, Putti, C, Semenzato, G, Agostini, C, D'Angelo, P, Izzi, G, Bertolini, P, Zecca, M, Marseglia, G, Maccario, R, Felici, L, Favre, C, Vecchi, V, Sacchini, P, Rinaldi, G, Livadiotti, S, Simonetti, A, Stabile, A, Duse, M, Iacobini, M, Quinti, I, Fiorilli, M, Moschese, V, Cecere, F, D'Ambrosio, A, De Zan, G, Strafella, S, Tamaro, P, Rabusin, M, Tommasini, A, Tovo, P, De Carli, M, De Carli, S, Nespoli, L, Marinoni, M, Porcellini, A, Lunardi, C, Patuzzo, G, Boner, A, Degani, D, Cancrini, C, Puliafito, P, Digilio, Mc, Soresina, A, Martino, S, Rondelli, R, Consolini, R, Ruga, Em, Cardinale, F, Finocchi, A, Romiti, Ml, Martire, B, Bacchetta, R, Albano, V, Carotti, A, Specchia, F, Montin, D, Cirillo, E, Cocchi, G, Trizzino, A, Bossi, G, Milanesi, O, Azzari, C, Corsello, G, Pignata, C, Aiuti, Alessandro, Pietrogrande, Mc, Marino, B, Ugazio, Ag, Plebani, A, Rossi, P., Cancrini, Caterina, Puliafito, Pamela, Digilio, Maria Cristina, Soresina, Annarosa, Martino, Silvana, Rondelli, Roberto, Consolini, Rita, Ruga, Ezia Maria, Cardinale, Fabio, Finocchi, Andrea, Romiti, Maria Luisa, Martire, Baldassarre, Bacchetta, Rosa, Albano, Veronica, Carotti, Adriano, Specchia, Fernando, Montin, Davide, Cirillo, Emilia, Cocchi, Guido, Trizzino, Antonino, Bossi, Grazia, Milanesi, Ornella, Azzari, Chiara, Corsello, Giovanni, Pignata, Claudio, Pietrogrande, Maria Cristina, Marino, Bruno, Ugazio, Alberto Giovanni, Plebani, Alessandro, Rossi, Paolo, Aiuti, A, Rossi, P, Pierani, P, Gabrielli, A, Danieli, Mg, De Mattia, D, Sisto, C, Dammacco, F, Ranieri, G, Pession, A, Ricci, G, Minelli, P, Lougaris, V, Badolato, R, Cattaneo, R, Airò, P, Mura, Rm, Cossu, F, Del Giacco, S, Manconi, Pe, Consarino, C, Dello Russo, Am, Miniero, R, Anastasio, E, Marino, S, Russo, G, Paganelli, R, Sperlì, D, Carpino, L, Aricò, M, Gambineri, E, Lippi, F, Canessa, C, Maggi, E, Romagnani, S, Matucci, A, Vultaggio, A, Gattorno, M, Castagnola, E, Nigro, G, Presta, G, Civino, A, Buzi, F, Gambaretto, G, Fasoli, S, Salpietro, C, Gallizzi, R, Dellepiane, Rm, Panisi, C, Fabio, G, Carrabba, M, Pietrogrande, M, Roncarolo, Mg, Biondi, A, Vallinoto, C, Poggi, V, Menna, G, Di Nardo, R, Sottile, R, Marone, G, Spadaro, G, Carli, M, Basso, G, Putti, C, Semenzato, G, Agostini, C, D'Angelo, P, Izzi, G, Bertolini, P, Zecca, M, Marseglia, G, Maccario, R, Felici, L, Favre, C, Vecchi, V, Sacchini, P, Rinaldi, G, Livadiotti, S, Simonetti, A, Stabile, A, Duse, M, Iacobini, M, Quinti, I, Fiorilli, M, Moschese, V, Cecere, F, D'Ambrosio, A, De Zan, G, Strafella, S, Tamaro, Paolo, Rabusin, M, Tommasini, A, Tovo, P, De Carli, M, De Carli, S, Nespoli, L, Marinoni, M, Porcellini, A, Lunardi, C, Patuzzo, G, Boner, A, Degani, D., Cancrini, C., Pulisfito, P., Digilio, M. C., Soresina, A., Martino, S., Rondelli, R., Consolini, R., Ruga, E. M., C. a. r. d. i. n. a. l. e., F., Finocchi, A., Romiti, M. L., Martire, B., Bacchetta, R., Albano, V., Carotti, A., Specchia, F., Montin, D., Cocchi, G., Trizzino, A., Bossi, G., Milanesi, O., Azzari, C., Corsello, G., Aiuti, A., Pietrogrande, M. C., Marino, B., Ugazio, A. G., Plebani, A., Digilio, MC, Ruga, EM, Romiti, ML, trizzino, A, Aiuti, Pietrogrande, MC, and Ugazio, AG

Subjects
Male, Pediatrics, 22q11.2 deletion, Delayed Diagnosis, Time Factors, Chromosomes, Human, Pair 22, Developmental Disabilities, digeorge syndrome, Sex Factor, Severity of Illness Index, Retrospective Studie, DiGeorge syndrome, Early Diagnosi, Age Factor, Prospective Studies, Neonatal hypocalcemia, Prospective cohort study, Child, medicine.diagnostic_test, Delayed Diagnosi, Primary immune disorders, Age Factors, del 22q, MIM, Abnormalities, Multiple, Adolescent, Adult, Child, Preschool, DiGeorge Syndrome, Early Diagnosis, Female, Follow-Up Studies, Genetic Testing, Humans, Infant, Infant, Newborn, Monitoring, Physiologic, Retrospective Studies, Risk Assessment, Sex Factors, Young Adult, Disease Progression, Cohort, Abnormalities, Multiple, Pediatrics, Perinatology and Child Health, Human, medicine.medical_specialty, Time Factor, Monitoring, Developmental Disabilitie, Italian Association of Pediatric Haematology and Oncology, Context (language use), Chromosomes, Follow-Up Studie, Severity of illness, medicine, 22q11DS, 22q11.2 deletion syndrome, AIEOP, Mendelian Inheritance in Man, Preschool, Physiologic, Genetic testing, Settore MED/38 - Pediatria Generale e Specialistica, business.industry, Retrospective cohort study, medicine.disease, Newborn, Prospective Studie, Pair 22, business
Abstract

Objective To investigate the clinical manifestations at diagnosis and during follow-up in patients with 22q11.2 deletion syndrome to better define the natural history of the disease. Study design A retrospective and prospective multicenter study was conducted with 228 patients in the context of the Italian Network for Primary Immunodeficiencies. Clinical diagnosis was confirmed by cytogenetic or molecular analysis. Results The cohort consisted of 112 males and 116 females; median age at diagnosis was 4 months (range 0 to 36 years 10 months). The diagnosis was made before 2 years of age in 71% of patients, predominantly related to the presence of heart anomalies and neonatal hypocalcemia. In patients diagnosed after 2 years of age, clinical features such as speech and language impairment, developmental delay, minor cardiac defects, recurrent infections, and facial features were the main elements leading to diagnosis. During follow-up (available for 172 patients), the frequency of autoimmune manifestations ( P = .015) and speech disorders ( P = .002) increased. After a median follow-up of 43 months, the survival probability was 0.92 at 15 years from diagnosis. Conclusions Our data show a delay in the diagnosis of 22q11.2 deletion syndrome with noncardiac symptoms. This study provides guidelines for pediatricians and specialists for early identification of cases that can be confirmed by genetic testing, which would permit the provision of appropriate clinical management.

Published
2014

4. The Quality of Life of Children and Adolescents with X-Linked Agammaglobulinemia

Author

Soresina A., Nacinovich R., Bomba M., Cassani M., Molinaro A., Sciotto A., Martino S., Cardinale F., De Mattia D., Putti C., Dellepiane R.M., Felici L., Parrinello G., Neri F., Plebani A., Pierani P., DeMattia D., Martire B., Armenio L., Dammacco F., Ranieri G., Masi M., Miniaci A., Pession A., Rondelli R., Notarangelo L. D., Cao, Cossu F., Del Giacco S., Manconi P., Evangelista I., Magro S., Morgione S., STRISCIUGLIO, PIETRO, Anastasio E., Schillirò G., Paganelli R., Sticca M., Sperlì D., Carpino L., Bernini G., Azzari C., Maggi E., Romagnani S., Matucci A., Vultaggio A., Castagnola E., Gattorno M., Presta G., Civino A., Gambaretto G., Fasoli S., Salpietro C., Pietrogrande M.C., DellePiane R.M., Panisi C., Cambiaghi G., Pietrogrande M., Roncarolo M.G., Aiuti A., Masera G., Biondi A., Sala A., PIGNATA, CLAUDIO, Poggi V., Menna G., Di Nardo R., D'Apuzzo A., Pelliccia A., Correra A., Marone G., SPADARO, GIUSEPPE, Carli M., Zanesco L., Basso G., Putti M.C., Semenzato G., Agostini C., Amato G.M., Aricò M., Trizzino A., Izzi G., Bertolini P., Locatelli F., Zecca M., Rondini G., Marseglia G.L., Maccario R., Bossi G., Favre C., Consolini R., Vecchi V., Sacchini P., Rinaldi G., Ugazio A.G., Rossi P., Livadiotti S., Cancrini C., Finocchi A., Stabile A., Duse M., Iacobini M., Quinti I., Moschese V., Cecere F., Morgese G., Acquaviva A., De Zan G., Strafella S., Tamaro P., Rabusin M., Tovo P.A., Nespoli L., Marinoni M., Porcellini A., Cazzola G.A., Annarosa, Soresina, Renata, Nacinovich, Monica, Bomba, Morena, Cassani, Molinaro, Anna, Antonella, Sciotto, Silvana, Martino, Fabio, Cardinale, Domenico, Mattia, Caterina, Putti, Rosa Maria, Dellepiane, Leonardo, Felici, Giovanni, Parrinello, Francesca, Neri, Alessandro, Plebani, Soresina, A, Nacinovich, R, Bomba, M, Cassani, M, Molinaro, A, Sciotto, A, Martino, S, Cardinale, F, De Mattia, D, Putti, C, Dellepiane, R, Felici, L, Parrinello, G, Neri, F, Plebani, A, Soresina, A., Nacinovich, R., Bomba, M., Cassani, M., Molinaro, A., Sciotto, A., Martino, S., Cardinale, F., De Mattia, D., Putti, C., Dellepiane, R. M., Felici, L., Parrinello, G., Neri, F., Plebani, A., Pierani, P., Demattia, D., Martire, B., Armenio, L., Dammacco, F., Ranieri, G., Masi, M., Miniaci, A., Pession, A., Rondelli, R., Notarangelo, L. D., Cao, Cossu, F., Del Giacco, S., Manconi, P., Evangelista, I., Magro, S., Morgione, S., Strisciuglio, Pietro, Anastasio, E., Schillirò, G., Paganelli, R., Sticca, M., Sperlì, D., Carpino, L., Bernini, G., Azzari, C., Maggi, E., Romagnani, S., Matucci, A., Vultaggio, A., Castagnola, E., Gattorno, M., Presta, G., Civino, A., Gambaretto, G., Fasoli, S., Salpietro, C., Pietrogrande, M. C., Panisi, C., Cambiaghi, G., Pietrogrande, M., Roncarolo, M. G., Aiuti, A., Masera, G., Biondi, A., Sala, A., Pignata, Claudio, Poggi, V., Menna, G., Di Nardo, R., D'Apuzzo, A., Pelliccia, A., Correra, A., Marone, G., Spadaro, Giuseppe, Carli, M., Zanesco, L., Basso, G., Putti, M. C., Semenzato, G., Agostini, C., Amato, G. M., Aricò, M., Trizzino, A., Izzi, G., Bertolini, P., Locatelli, F., Zecca, M., Rondini, G., Marseglia, G. L., Maccario, R., Bossi, G., Favre, C., Consolini, R., Vecchi, V., Sacchini, P., Rinaldi, G., Ugazio, A. G., Rossi, P., Livadiotti, S., Cancrini, C., Finocchi, A., Stabile, A., Duse, M., Iacobini, M., Quinti, I., Moschese, V., Cecere, F., Morgese, G., Acquaviva, A., De Zan, G., Strafella, S., Tamaro, P., Rabusin, M., Tovo, P. A., Nespoli, L., Marinoni, M., Porcellini, A., and Cazzola, G. A.

Subjects
Male, Pediatrics, medicine.medical_specialty, x-linked agammaglobulinemia, Activities of daily living, Adolescent, X-linked agammaglobulinemia, Health Status, Immunology, pedsql 4.0 generic core scale, Quality of life, children, Agammaglobulinemia, Surveys and Questionnaires, Activities of Daily Living, health-related quality of life, parents, medicine, Humans, Immunology and Allergy, PedsQL 4.0 Generic Core Scale, Child, Settore MED/38 - Pediatria Generale e Specialistica, Health related quality of life, quality of live, business.industry, Immunoglobulins, Intravenous, Genetic Diseases, X-Linked, medicine.disease, Socioeconomic Factors, Child, Preschool, Mutation, Quality of Life, Female, X-linked agammaglobulinemia - children - parents - health-related quality of life - PedsQL 4.0 Generic Core Scale, business
Abstract

Introduction: The health-related quality of life in X-linked agammaglobulinemia was investigated in 25 children and adolescents patients through the Italian version of Pediatric Quality of Life Inventory 4.0 Generic Core Scale for patients aged less then 18 years, comparing child perception to that of the parents and the physician's evaluation. The data were compared with the ones of 80 healthy controls and the literature data of a group of patients with rheumatic diseases. Discussion: The agammaglobulinemia subjects perceived a lower global quality of life than the healthy subjects, but significantly higher than the rheumatic diseases controls. The clinical relevance of health-related quality of life assessment in X-linked agammaglobulinemia pediatric patients is discussed. © 2008 Springer Science+Business Media, LLC.

Published
2009

5. Restriction in T-cell receptor repertoire in a patient affected by trichothiodystrophy and CD4+ lymphopenia

Author

Cancrini, C, Romiti, Ml, Di Cesare, S, Angelini, F, Gigliotti, D, Livadiotti, S, Bertini, E, Rossi, P, Racioppi, L, Cancrini, C, Romiti, Ml, DI CESARE, S, Angelini, F, Gigliotti, D, Livadiotti, S, Bertini, E, Rossi, P, and Racioppi, Luigi

Subjects
CD4-Positive T-Lymphocytes, Male, CD4 antigen, CD8 antigen, T lymphocyte receptor, article, case report, evaluation, homeostasis, human, immune system, infant, lymphocytopenia, male, measurement, molecular biology, priority journal, regulatory mechanism, T lymphocyte, trichothiodystrophy, ATP-Binding Cassette Transporters, Case-Control Studies, Child, Preschool, Gene Rearrangement, T-Lymphocyte, Hair Diseases, Humans, Lymphopenia, Receptors, Antigen, T-Cell, Receptors, Child, Preschool, Gene Rearrangement, Settore MED/38 - Pediatria Generale e Specialistica, T-Cell, T-Lymphocyte, Antigen
Published
2002

6. Human immunodeficiency virus-related cancer in children: incidence and treatment outcome--report of the Italian Register

Author

Caselli D, Klersy C, de Martino M, Gabiano C, Galli L, Tovo PA, Aricò M, Giaquinto C. Giacomet V, Castelli Gattinara G, Livadiotti S, Minoli L, Maccabruni A, Fundarò C, Osimani P, De maria A, Rossi G, Dessì C, Viganò A, Plebani A, Riva C, De mattia D, Salvatore C, Mazza A., GUARINO, ALFREDO, Caselli, D, Klersy, C, de Martino, M, Gabiano, C, Galli, L, Tovo, Pa, Aricò, M, Giaquinto C., Giacomet V, Castelli Gattinara, G, Livadiotti, S, Minoli, L, Maccabruni, A, Fundarò, C, Osimani, P, Guarino, Alfredo, De maria, A, Rossi, G, Dessì, C, Viganò, A, Plebani, A, Riva, C, De mattia, D, Salvatore, C, and Mazza, A.

Subjects
Male, Cancer Research, medicine.medical_specialty, Pediatrics, Adolescent, HIV Infections, Acquired immunodeficiency syndrome (AIDS), Pregnancy, Neoplasms, Epidemiology, medicine, Humans, Prospective Studies, Registries, Risk factor, Sida, Child, Lymphoma, AIDS-Related, Acquired Immunodeficiency Syndrome, Perinatal Exposure, biology, business.industry, Incidence (epidemiology), Incidence, Lymphoma, Non-Hodgkin, Infant, Newborn, Infant, biology.organism_classification, medicine.disease, Infectious Disease Transmission, Vertical, Surgery, Treatment Outcome, Oncology, El Niño, Italy, Child, Preschool, Female, Viral disease, business
Abstract

PURPOSE: To outline the incidence, presenting features, treatment response, and outcome of human immunodeficiency virus (HIV)–associated malignancies in infancy and childhood, together with the estimated risk of HIV-associated cancer in children born to mothers infected with HIV. PATIENTS AND METHODS: The Italian Register for HIV Infection in Children collected data by specific registration and follow-up forms. By March 1999, 5,060 children were recruited, including 4,889 with perinatal exposure to HIV-1. Overall, 1,331 infected children were enrolled onto the Register and classified according to current Centers for Disease Control criteria; of them, 1,163 were vertically infected (24% of those with perinatal exposure). Of these 1,163, 569 (49%) were considered to have been prospectively followed-up since they had been registered at birth or within the first 3 months of age. RESULTS: Of the 1,331 children observed for a median time of 6.5 years, 35 developed 36 malignancies, four of which occurred in patients with blood-borne risk. For the 1,163 vertically infected children, the cumulative number of years of observation was 7,178 child-years and the cumulative incidence of HIV-associated tumors was 4.18 per 1,000 children/yr (95% confidence interval [CI], 2.92 to 5.98). When only the 569 vertically infected children prospectively followed up since birth were considered, the cumulative number of years of observation was 2,803 child-years. In this group, 10 tumors were observed, with a cumulative incidence of HIV-associated tumors of 3.57 per 1,000 children per year (95% CI, 1.92 to 6.63). CONCLUSION: The risk of cancer was significantly higher but not restricted to symptomatic and/or immune-compromised children. Cancer-directed treatment should be given promptly to these patients, who have a fair chance to survive their tumor in view of potential highly aggressive antiretroviral therapy–associated improvement in survival and quality of life.

Published
2000

10. A hypermorphic I kappa B alpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency

Author

Courtois, G, Smahi, A, Reichenbach, J, Doffinger, R, Cancrini, C, Bonnet, M, Puel, A, Chable Bessia, C, Yamaoka, S, Feinberg, J, Dupuis Girod, S, Bodemer, C, Livadiotti, S, Novelli, F, Rossi, P, Fischer, A, Israel, A, Munnich, A, Le Deist, F, and Casanova, Jl

Subjects
Male, CD40 ligand, complementary DNA, cytokine, genomic DNA, I kappa B alpha, I kappa B kinase, I kappa B kinase gamma, immunoglobulin enhancer binding protein, interleukin 18, interleukin 1beta, T lymphocyte receptor, tumor necrosis factor alpha, tumor necrosis factor receptor, unclassified drug, CHUK protein, human, I kappa B, I kappa B beta, IKBKB protein, human, IKBKE protein, human, lymphocyte antigen receptor, protein serine threonine kinase, anhidrosis, anhidrotic ectodermal dysplasia, article, autosomal dominant disorder, case report, cellular immunity, controlled study, disease association, ectodermal dysplasia, gene, gene mutation, human, human cell, IKBA gene, immune deficiency, immunogenetics, infant, male, priority journal, T lymphocyte, X chromosome linked disorder, child, genetic transcription, genetics, immunology, mutation, physiology, signal transduction, Child, Ectodermal Dysplasia, Humans, I-kappa B Kinase, I-kappa B Proteins, Immunologic Deficiency Syndromes, Mutation, NF-kappa B, Protein-Serine-Threonine Kinases, Receptor-CD3 Complex, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Transcription, Genetic, Tumor Necrosis Factor-alpha, Receptor-CD3 Complex, Antigen, IKBKE protein, Transcription, Genetic, Settore MED/38 - Pediatria Generale e Specialistica, CHUK protein, T-Cell, IKBKB protein
Published
2003

13. X-chromosome inactivation and mutation pattern in the Bruton's tyrosine kinase gene in patients with X-linked agammaglobulinemia. Italian XLA Collaborative Group

Author

Moschese, V., Orlandi, P., Plebani, A., Arvanitidis, K., Fiorini, M., Speletas, M., Mella, P., Ritis, K., Sideras, P., ANDREA FINOCCHI, Livadiotti, S., and Rossi, P.

Subjects
Settore MED/38 - Pediatria Generale e Specialistica, Male, DNA, Complementary, X Chromosome, Genetic Linkage, Agammaglobulinemia, Humans, Protein-Tyrosine Kinases, Sequence Analysis, DNA, Polymerase Chain Reaction, Ribonucleases, Dosage Compensation, Genetic, Mutation, Female, DNA, Genetic, Complementary, hemic and lymphatic diseases, Dosage Compensation, Agammaglobulinaemia Tyrosine Kinase, Sequence Analysis, Research Article
Abstract

BACKGROUND: The diagnosis of X-linked agammaglobulinemia (XLA) is not always clearcut. Not all XLA conform to the classic phenotype and less than 50% of affected boys have a family history of immunodeficiency. Mutations in the gene for Bruton's tyrosine kinase (BTK) are responsible for the majority of agammaglobulinemia cases. However, a certain proportion of patients may have mutations involving other genes, although they show with an XLA phenotype. We performed BTK gene mutation analysis in 37 males with presumed XLA and analyzed the pattern of X-chromosome inactivation (XCI) in 31 mothers to evaluate the relevance of these approaches to diagnosis and genetic counseling. MATERIALS AND METHODS: Twenty affected males with a sporadic occurrence and 17 familial cases belonging to nine families were enrolled within the framework of the Italian Multicenter Clinical Study on XLA. We used non-isotopic RNase cleavage assay (NIRCA), followed by cDNA sequence determination to screen for BTK mutations and X-chromosome inactivation analysis for carrier detection. RESULTS: Using the cDNA-based approach, the identification of BTK gene abnormalities confirmed the clinical diagnosis of XLA in 31 of 37 affected infants. Missense was the most frequent mutational event and the kinase domain was mostly involved. In addition, nine novel mutations were identified. In sporadic cases, BTK gene abnormalities were identified in 9 out of 10 patients whose mothers had a nonrandom pattern of XCI and in 5 out of 6 patients whose mother had a random pattern of XCI. With the exception of one family, all patients with a familial occurrence and born to mothers with a nonrandom pattern of XCI had mutations of the BTK gene. CONCLUSIONS: Our findings indicate that in sporadic cases BTK gene sequencing is the only reliable tool for a definitive diagnosis of XLA and support XCI as the first diagnostic tool in the mothers of affected males in multiple generations. Furthermore, our molecular analysis confirms that 10-20% of BTK-unaltered patients have disorders caused by defects in other genes.

Published
2000

17. HIV-1 transmission through breast-milk: appraisal of risk according to duration of feeding

Author

de Martino M, Pa, Tovo, Ae, Tozzi, Patrizio Pezzotti, Galli L, Livadiotti S, Caselli D, Massironi E, Ruga E, and Fioredda F

Subjects
Male, Breast Feeding, Time Factors, Italy, Milk, Human, Risk Factors, HIV-1, Infant, Newborn, Humans, Infant, Female, HIV Infections, Follow-Up Studies
Abstract

To estimate the risk of HIV-1 transmission through breast-milk in children born to infected mothers, and to determine the relationship between duration of breast-feeding and risk.The study population included 168 breast-fed and 793 bottle-fed children born to seropositive mothers. All subjects were enrolled and followed-up in the Italian Register for HIV Infection in Children; HIV sero-status was defined in all children. Multivariate analysis was performed using a logistic regression model. Independent variables included biological factors (duration of breast-feeding, gestational age, clinical condition of mother at delivery, mode of delivery, birth-weight and sex). Year of birth and age when HIV infection was diagnosed were also considered in the analysis attempting to control for possible selection biases.Breast-feeding increased the risk of HIV-1 transmission. The estimated adjusted odds ratio for 1 day of breast- versus bottle-feeding was 1.19 (95% confidence interval, 1.10-1.28). The infection odds ratio of breast- versus bottle-feeding increased with the natural logarithm of the duration of practice.These results are the first to provide an appraisal of the additional risk of HIV-1 transmission associated with a seropositive mother breast-feeding her child. Biological significance of this route of transmission was supported by demonstration of a relationship between duration of breast-feeding and risk of HIV-1 transmission.

Published
1992

18. Predictive value of the HIV paediatric classification system for the long-term course of perinatally infected children

Author

Galli, L., Martino, M., Tovo, P. -A, Gabiano, C., Zappa, M., Osimani, P., Mattia, D., Zizzadoro, P., Ruggeri, M., Baldi, F., Ciccia, M., Dallacasa, P., Masi, M., Battisti, L., Bresciani, E., Duse, M., Timpano, S., Chiriacò, P. G., Belloni, M., Corrias, A., Ibba, P., Rossi, G., Anastasio, E., Sabatino, G., Sticca, M., Nasi, C., Bezzi, T., Vierucci, A., Farina, S., Ballotti, S., Bassetti, D., Maria, A., Forni, G. L., Gotta, C., Marazzi, M. G., Mecca, D., Tasso, L., Tondo, U., Micheletti, E., Gambaretto, G., Cellini, M., Altobelli, R., Bucceri, A., Conio, S., Ferraris, G., Giovannini, M., Lipreri, R., Paola Giovanna Marchisio, Massironi, E., Pinzani, R., Plebani, A., Rancilio, L., Riva, E., Salvini, F., Tornaghi, R., Zuccotti, G. V., Guarino, A., Pignata, C., Giaquinto, C., Rampon, O., Ruga, E. M., Romano, A., Benaglia, G., Caselli, D., Maccabruni, A., Bassanetti, F., Consolini, R., Palla, G., Antonellini, A., Metri, A. M., Magnani, C., Cecchi, M. T., Castelli Gattinara, G., Catania, S., Falconieri, P., Fundarò, C., Genovese, O., Krzisztofiak, A., Livadiotti, S., Rendeli, C., Stegagno, M., Timpano, C., Mazza, A., Salvatore, C. M., Palomba, E., Riva, C., Tulisso, S., and Pellegatta, A.

19. KeyNote: Discoverer - Making commercial satellite operations in very low earth orbit a reality

Author

Roberts, P. C. E., Crisp, N. H., Romano, F., Herdrich, G. H., Oiko, V. T. A., Edmondson, S., Haigh, S. J., Huyton, C., Livadiotti, S., Lyons, R. E., Smith, K. L., Sinpetru, L. A., Straker, A., Worral, S. D., Becedas, J., Domínguez, R. M., González, D., Cañas, V., Hanessian, V., Mølgaard, A., Nielsen, J., Bisgaard, M., Boxberger, A., Chan, Y. -A, Fasoulas, S., Traub, C., Garcia-Almiñana, D., Silvia Rodriguez-Donaire, Sureda, M., Kataria, D., Outlaw, R., Belkouchi, B., Conte, A., Perez, J. S., Villain, R., Heißerer, B., and Schwalber, A.

20. Attitude control for satellites flying in VLEO using aerodynamic surfaces

Author

Munoz, V. C., Gonzalez, D., Becedas, J., Dominguez, R. M., Roberts, P. C. E., Crisp, N. H., Oiko, V. T. A., Edmondson, S., Worrall, S. D., Haigh, S., Smith, K., Lyons, R. E., Livadiotti, S., Huyton, C., Sinpetru, L. A., Rodriguez-Donaire, S., Garcia-Alminana, D., Nieto, M., Munoz, C., Miquel Sureda, Kataria, D., Herdrich, G. H., Romano, F., Binder, T., Boxberger, A., Fasoulas, S., Traub, C., Outlaw, R., Hanessian, V., Morsbol, J., Villain, R., Perez, J. S., Conte, A., Belkouchi, B., Schwalber, A., and Heisserer, B.

22. RF helicon-based plasma thruster (IPT): Design, set-up, and first ignition

Author

Romano, F., Chan, Y. -A, Herdrich, G., Roberts, P. C. E., Traub, C., Fasoulas, S., Crisp, N., Edmondson, S., Haigh, S., Holmes, B. A., Livadiotti, S., Alejandro Macario Rojas, Abrao Oiko, V. T., Smith, K., Sinpetru, L., Becedas, J., Dominguez, R. M., Christensen, S., Jensen, T. K., Nielsen, J., Bisgaard, M., Garcia-Almiñana, D., Rodriguez-Donaire, S., Sureda, M., Garcia-Berenguer, M., Kataria, D., Villain, R., Seminari, S., Conte, A., and Belkouchi, B.

Subjects
ResearchInstitutes_Networks_Beacons/dalton_nuclear_institute, Dalton Nuclear Institute
Abstract

To extend missions lifetime at very low altitudes, an efficient propulsion system is required to compensate for aerodynamic drag. One solution is Atmosphere-Breathing Electric Propulsion (ABEP). It collects atmospheric particles to be used as propellant for an electric thruster. The system ideally nullifies the requirement of onboard propellant storage. An ABEP system can be applied to any celestial body with atmosphere (Mars, Venus, Titan, etc.), enabling new mission at low altitude ranges for longer times. Challenging is operation of the thruster on reactive chemical species, such as atomic oxygen (AO), that is highly present in low Earth orbit, as they cause erosion of (not only) propulsion system components, i.e. acceleration grids, electrodes, neutralizers, and discharge channels of conventional EP systems. For this reason, a contactless plasma thruster is developed: the RF helicon-based plasma thruster (IPT). The paper describes the thruster design, implementation, and first ignition tests. The thruster presents a novel antenna called the birdcage antenna that is implemented for decades in magnetic resonance imaging (MRI) machines. The design is supported by the simulation tool XFdtd®. The IPT is aided by an externally applied static magnetic field that provides the boundary condition for the helicon wave formation within the plasma discharge. The antenna working principle allows to minimize losses in the electric circuit and provides, together with the applied magnetic field, acceleration of a quasi-neutral plasma plume.

23. Visceral leishmaniasis revealing chronic granulomatous diseases in a child

Author

Finocchi, A., Paolo Palma, Di Matteo, G., Chiriaco, M., Lancella, L., Simonetti, A., Rana, I., Livadiotti, S., and Rossi, P.

Subjects
Bone marrow transplant, Children, Chronic granulomatous disease, Immunodeficiency, Visceral leishmaniasis, Settore MED/38 - Pediatria Generale e Specialistica

24. Demonstration of aerodynamic control manoeuvres in very low earth orbit using SOAR (Satellite for Orbital Aerodynamics Research)

Author

Crisp, N. H., Livadiotti, S., Roberts, P. C. E., Edmondson, S., Haigh, S. J., Huyton, C., Lyons, R. E., Oiko, V. T. A., Smith, K. L., Sinpetru, L. A., Straker, A., Worral, S. D., Becedas, J., Domínguez, R. M., González, D., Cañas, V., Hanessian, V., Mølgaard, A., Nielsen, J., Bisgaard, M., Boxberger, A., Chan, Y. -A, Herdrich, G. H., Francesco Romano, Fasoulas, S., Traub, C., Garcia-Almiñana, D., Rodriguez-Donaire, S., Sureda, M., Kataria, D., Outlaw, R., Belkouchi, B., Conte, A., Perez, J. S., Villain, R., Heißerer, B., and Schwalber, A.

25. Discoverer: Developing technologies to enable commercial satellite operations in very low earth orbit

Author

Roberts, P. C. E., Crisp, N. H., Edmondson, S., Haigh, S. J., Holmes, B. E. A., Livadiotti, S., Macario-Rojas, A., Oiko, V. T. A., Smith, K. L., Sinpetru, L. A., Becedas, J., Domínguez, R. M., Sulliotti-Linner, V., Christensen, S., Jensen, T. K., Nielsen, J., Bisgaard, M., Chan, Y. -A, Herdrich, G. H., Romano, F., Fasoulas, S., Traub, C., Garcia-Almiñana, D., Garcia-Berenguer, M., Rodriguez-Donaire, S., Miquel Sureda, Kataria, D., Belkouchi, B., Conte, A., Seminari, S., Villain, R., and Schwalber, A.

Subjects
ResearchInstitutes_Networks_Beacons/dalton_nuclear_institute, Dalton Nuclear Institute
Abstract

The DISCOVERER project is developing technologies to enable commercially-viable sustained-operation of satellites in very low Earth orbits for communications and remote sensing applications. Operating closer to the surface of the Earth significantly reduces latency for communications applications and improves link budgets, whilst remote sensing also benefits from improved link budgets, the ability to have higher resolution or smaller instruments, all of which provide cost benefits. In addition, all applications benefit from increased launch mass to lower altitudes, whilst end-of-life removal is ensured due to the increased atmospheric drag. However, this drag must also be minimised and compensated for. DISCOVERER is developing several critical technologies to enable commercially viable operations in at these lower altitudes including aerodynamic materials, aerodynamic attitude and orbit control methods, atmosphere breathing electric propulsion and an in-situ environment monitoring payload. The current status of these developments are summarised, along with the plans for the coming year.

26. Ground-based experimental facility for orbital aerodynamics research: Design, construction and characterisation

Author

Oiko, V. T. A., Roberts, P. C. E., Macario-Rojas, A., Edmondson, S., Haigh, S. J., Holmes, B. E. A., Livadiotti, S., Crisp, N. H., Smith, K. L., Sinpetru, L. A., Becedas, J., Domínguez, R. M., Sulliotti-Linner, V., Christensen, S., Jensen, T. K., Nielsen, J., Bisgaard, M., Chan, Y. -A, Herdrich, G. H., Romano, F., Fasoulas, S., Traub, C., Garcia-Almiñana, D., Garcia-Berenguer, M., Rodriguez-Donaire, S., Sureda, M., Dhiren Kataria, Belkouchi, B., Conte, A., Seminari, S., and Villain, R.

Subjects
ResearchInstitutes_Networks_Beacons/dalton_nuclear_institute, Dalton Nuclear Institute
Abstract

In very low Earth orbits (VLEO), below 450 km altitude, the aerodynamic properties of satellites are primarily determined by the flow regime, free molecular flow, and the interaction of atomic oxygen with the surfaces of the spacecraft. The Rarefied Orbital Aerodynamics Research (ROAR) facility is a novel experimental facility designed to simulate these conditions in a controlled environment to characterise the aerodynamic properties of materials. It is built as part of DISCOVERER, a Horizon 2020 project developing the different technologies required to enable the sustainable operation of satellites in VLEO. Because ROAR isn’t intended to perform erosion studies, it differs quite significantly from other atomic oxygen exposure experiments and its characteristics are discussed in this work. ROAR consists of an ultrahigh vacuum system, responsible for generating the free molecular flow conditions, a source of hyperthermal oxygen atoms at orbital velocities, and mass spectrometers; the latter used to characterise the gas-surface interactions, and therefore the material’s aerodynamic performance. This paper includes a description of ROAR’s main components, together with the experimental methodology for materials testing and early results. Among the main parameters to be considered are atomic oxygen flux, beam shape and energy spread, mass resolution, and signal-tonoise ratio.

27. Concepts and applications of aerodynamic attitude and orbital control for spacecraft in very low earth orbit

Author

Livadiotti, S., Crisp, N. H., Roberts, P. C. E., Edmondson, S., Haigh, S. J., Huyton, C., Lyons, R. E., Oiko, V. T. A., Smith, K. L., Sinpetru, L. A., Straker, A., Worral, S. D., Becedas, J., Domínguez, R. M., González, D., Cañas, V., Hanessian, V., Mølgaard, A., Nielsen, J., Bisgaard, M., Boxberger, A., Chan, Y. -A, Herdrich, G. H., Romano, F., Fasoulas, S., Traub, C., Garcia-Almiñana, D., Silvia Rodriguez-Donaire, Sureda, M., Kataria, D., Outlaw, R., Belkouchi, B., Conte, A., Perez, J. S., Villain, R., Heißerer, B., and Schwalber, A.

28. Investigation of novel drag-reducing and atomic oxygen resistant materials in very low earth orbit using SOAR (Satellite for orbital aerodynamics research)

Author

Crisp, N. H., Alejandro Macario Rojas, Roberts, P. C. E., Edmondson, S., Haigh, S. J., Holmes, B. E. A., Livadiotti, S., Oiko, V. T. A., Smith, K. L., Sinpetru, L. A., Becedas, J., Domínguez, R. M., Sulliotti-Linner, V., Christensen, S., Jensen, T. K., Nielsen, J., Bisgaard, M., Chan, Y. -A, Herdrich, G. H., Romano, F., Fasoulas, S., Traub, C., Garcia-Almiñana, D., Garcia-Berenguer, M., Rodriguez-Donaire, S., Sureda, M., Kataria, D., Belkouchi, B., Conte, A., Seminari, S., and Villain, R.

29. Inductive plasma thruster (IPT) design for an atmosphere-breathing electric propulsion system (ABEP)

Author

Romano, F., Herdrich, G., Roberts, P. C. E., Chan, Y. -A, Traub, C., Fasoulas, S., Smith, K., Edmondson, S., Haigh, S., Nicholas Crisp, Abrao Oiko, V. T., Lyons, R., Worrall, S. D., Livadiotti, S., Huyton, C., Sinpetru, L., Outlaw, R., Becedas, J., Dominguez, R. M., González, D., Hanessian, V., Mølgaard, A., Nielsen, J., Bisgaard, M., Garcia-Almiñana, D., Rodriguez-Donaire, S., Sureda, M., Kataria, D., Villain, R., Santiago Perez, J., Conte, A., Belkouchi, B., Schwalber, A., Heißerer, B., Magarotto, M., and Pavarin, D.

30. Early Results from the DISCOVERER Project

Author

Roberts, P. C. E., Crisp, N. H., Oiko, V. T. A., Edmondson, S., Romano, F., Rodriguez-Donaire, S., Garcia-Almiñana, D., Haigh, S. J., Holmes, B. E. A., Livadiotti, S., Macario-Rojas, A., Smith, K. L., Sinpetru, L. A., Becedas, J., Sulliotti-Linner, V., Christensen, S., Jensen, T. K., Nielsen, J., Bisgaard, M., Chan, Y. -A, Georg Herdrich, Fasoulas, S., Traub, C., Sureda, M., Kataria, D., Belkouchi, B., Conte, A., Seminari, S., Villain, R., and Schwalber, A.

33. Early-onset monocyte-B-natural killer-dendritic cells’ deficiency successfully treated with hematopoietic stem cell transaplantation

Author

Samantha Scaramuzza, Maria Chiriaco, Luigi Racioppi, Maria Luisa Romiti, Giuseppe Palumbo, Paolo Palma, Susanna Livadiotti, Maurizio Caniglia, Rita Maria Pinto, Silvia Di Cesare, Caterina Cancrini, Rita De Vito, Lidia De Felice, Gigliola Di Matteo, Alessia Scarselli, Paolo Rossi, Alessandro Aiuti, Alain Fischer, Cancrini, C., Scarselli, A., Scaramuzza, S., Chiriaco, M., Di Cesare, S., Di Matteo, G., Romiti, M. L., Palma, P., De Felice, L., Palumbo, G., Pinto, R. M., De Vito, R., Racioppi, Luigi, Livadiotti, S., Fischer, A., Rossi, P., Caniglia, M., Aiuti, A., Cancrini, C, Scarselli, A, Scaramuzza, S, Chiriaco, M, Di Cesare, S, Di Matteo, G, Romiti, Ml, Palma, P, De Felice, L, Palumbo, G, Pinto, Rm, De Vito, R, Racioppi, L, Livadiotti, S, Fischer, A, Rossi, P, Caniglia, M, and Aiuti, Alessandro

Subjects
Settore MED/38 - Pediatria Generale e Specialistica, business.industry, medicine.medical_treatment, Monocyte, Immunology, LINEAGE, Hematopoietic stem cell transplantation, Immunologic Deficiency Syndromes, medicine.anatomical_structure, medicine, Immunology and Allergy, business, Early onset
Published
2011

34. A prospective, randomized study of empirical antifungal therapy for the treatment of chemotherapy-induced febrile neutropenia in children

Author

Mareva Giacchino, Simone Cesaro, Ottavio Ziino, Anna Pegoraro, Marcello Chiodi, Alfredo Pontillo, Fraia Melchionda, Nicola Santoro, Maurizio Aricò, Susanna Livadiotti, Giulio Andrea Zanazzo, Pietro Ragusa, Vincenzo Poggi, Désirée Caselli, Caselli, D, Cesaro, S, Ziino, O, Ragusa, P, Pontillo, A, Pegoraro, A, Santoro, N, Zanazzo, G, Poggi, V, Mareva, G, Livadiotti, S, Melchionda, F, Chiodi, M, and Aricò, M

Subjects
Male, medicine.medical_specialty, Antifungal Agents, Neutropenia, Antineoplastic Agents, Opportunistic Infections, Lower risk, Fever of Unknown Origin, law.invention, Echinocandins, Lipopeptides, chemistry.chemical_compound, Randomized controlled trial, Caspofungin, law, Amphotericin B, Internal medicine, medicine, Humans, Prospective Studies, Child, Prospective cohort study, empirical antifungal therapy, children, cancer, business.industry, Patient Selection, Infant, Cancer, Hematology, Length of Stay, medicine.disease, Confidence interval, Surgery, Hospitalization, Treatment Outcome, Mycoses, chemistry, Child, Preschool, Female, business, Empiric therapy, Febrile neutropenia
Abstract

Given that the rationale for empirical antifungal therapy in neutropenic children is limited and based on adult patient data, we performed a prospective, randomized, controlled trial that evaluated 110 neutropenic children with persistent fever. Those at high risk for invasive fungal infections (IFI) received caspofungin (Arm C) or liposomal amphotericinB (Arm B); those with a lower risk were randomized to receive Arm B, C, or no antifungal treatment (Arm A). Complete response to empirical antifungal therapy was achieved in 90/104 patients (86·5%): 48/56 at high risk (85·7%) [88·0% in Arm B; 83·9% in Arm C (P = 0·72)], and 42/48 at low risk (87·5%) [87·5% in control Arm A, 80·0% Arm B, 94·1% Arm C; (P = 0·41)]. None of the variables tested by multiple logistic regression analysis showed a significant effect on the probability to achieve complete response. IFI was diagnosed in nine patients (8·2%, 95% confidence interval, 3·8-15·0). This randomized controlled study showed that empirical antifungal therapy was of no advantage in terms of survival without fever and IFI in patients aged

Published
2012

35. Defective dendritic cell maturation in a child with nucleotide excision repair deficiency and CD4 lymphopenia

Author

M. G. Gambarara, Luigi Racioppi, Susanna Livadiotti, S Di Cesare, M. L. Romiti, F. Angelini, Maria Chiara Stefanini, Giuseppe Matarese, Enrico Bertini, F. Lago Paz, Paolo Rossi, Caterina Cancrini, Racioppi, Luigi, Cancrini, C, Romiti, Ml, Angelini, F, DI CESARE, S, Bertini, E, Livadiotti, S, Gambarara, Mg, Matarese, Giuseppe, LAGO PAZ, F, Stefanini, M, and Rossi, P.

Subjects
glycoprotein, CD4-Positive T-Lymphocytes, Male, DNA Repair, Cellular differentiation, cell maturation, Transcription Factors, TFII, photostimulation, Mental Retardation, antibody, T lymphocyte, Immunology and Allergy, immunopathology, Child, transcription factor, stimulus response, recombinant interleukin 2, disease course, pathogenesis, article, Ichthyosis, Cell Differentiation, Syndrome, Trichothiodystrophy (TTD), enzyme activity, DNA-Binding Proteins, priority journal, trichothiodystrophy, Child, Preschool, Transcription factor II H, signal transduction, cross linking, ultraviolet radiation, HLA antigen, dendritic cell, CD3, Immunology, T lymphocytes, cell stimulation, Genes, Recessive, mitogenic agent, Biology, CD86 antigen, FYN, Intellectual Disability, complex formation, Lymphopenia, Dendritic cells (DCs), Immunodeficiency, case report, Recessive, Humans, human, Photosensitivity Disorders, Antigen-presenting cell, Anergy, Combined immunodeficiency (CID), Preschool, protein expression, Xeroderma Pigmentosum Group D Protein, CD86, Settore MED/38 - Pediatria Generale e Specialistica, TFII, CD28 antigen, CD3 antigen, protein subunit, protein tyrosine kinase, T lymphocyte receptor, antigen presenting cell, cell proliferation, clinical feature, enzyme activation, flow cytometry, genetic transcription, human cell, immune deficiency, infant, lymphocytopenia, male, Dendritic Cells, DNA Helicases, Hair, Proteins, Severe Combined Immunodeficiency, Signal Transduction, Transcription Factor TFIIH, Transcription Factors, Dendritic cell, Genes, Cancer research, biology.protein
Abstract

SummaryWe report a case of a combined immunodeficiency (CID) in a child affected by trichothiodystrophy (TTD) characterized by an altered response to ultraviolet (UV) light due to a defect in the XPD gene. The XPD gene encodes a subunit of the transcription factor II H (TFIIH), a complex involved in nucleotide-excision repair (NER) and basal transcription. Our patient showed neurological and immune system abnormalities, including CD4 + lymphopenia never previously reported in TTD patients. In vitro immunological studies revealed a marked reduction in T-cell proliferation in response to mitogens and CD3 cross-linking which was partially recovered by the addition of anti-CD28 antibody or exogenous interleukin-2. The patient's T cells displayed alterations in T-cell receptor (TCR/CD3) proximal signalling characterized by marked reduction in Lck kinase activity coupled with a constitutive hyperactivation of Fyn kinase. Despite these alterations, normal levels of Lck and Fyn proteins were detected. The role of antigen-presenting cells (APCs) in the pathogenesis of the T-cell defect was investigated by analysing dendritic cells (DCs) generated from the patient's blood monocytes. In these cells, flow cytometry revealed significantly reduced expression of the CD86 co-stimulatory molecules and HLA glycoproteins. In addition, the patient's DCs showed a decreased ability to stimulate naive T lymphocytes. Overall, the results of our study suggest that a defective TFIIH complex might result in alterations in T cells and DC functions leading to a severe immunodeficiency.

Published
2001

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