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Human thymus: development and diseases

Abstract

The thymus continues to be a neglected organ, both in research and in clinical practice. Compared to bone marrow, in which intrinsic diseases and deleterious effects of drugs have been well explored, thymus has not received equivalent attention. This project continues a previous one named “Early-onset autoimmunity” (FAPESP grant 2008/58234-4), in which one of the subprojects dealt with functional study of thymus, and allowed assessment of the organ function in patients with Down syndrome and DiGeorge syndrome (22q11.2 deletion), two human chromosomopathies with thymic dysfunction. Considering: i) the numerous series of well-characterized patients followed-up at the Instituto da Criança, ii) access to a large number of thymus specimens, iii) availability of methods for morphological and functional study of the organ [measurement of TRECs (thymic recent emigrant cells) imaging techniques in clinical practice, microscopy, flow cytometry, gene expression platform, bioinformatics], in this new project, we intend to perform: 1) Morphological and functional assessment of thymus in healthy infants and children of various ages; 2) Study of global gene expression in the thymus, as well as network of interactions between genes in infants and children of various ages and in infants and children with Down syndrome (DS); 3) Characterization of B lymphocyte subpopulations in thymus of children of various ages with congenital heart disease as an isolated malformation, and in DS children; 4) Evaluation of phenotype-genotypic relationship and characterization of immune alterations in patients with typical and atypical 22q11.2 deletion; 5) Evaluation of morphological and functional thymic changes in children with primary immunodeficiencies and systemic autimmune diseases undergoing immunosuppressive therapy. It is expected to bring contributions to better knowledge of human thymus development as well as for pathophysiology of some primary and secondary thymic diseases, that may open possibilities for optimal management of affected patients. A new program of thymus transplant should be implemented at Instituto da Criança. It is also expected to simulate the interest of the physicians in the clinical exploration of the thymus. (AU)

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Scientific publications (24)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MARCÍLIA SIERRO GRASSI; MARÍLIA MONTENEGRO; EVELIN ALINE ZANARDO; ANTONIO CARLOS PASTORINO; MAYRA BARROS DORNA; CHONG KIM; MARCELO JATENE; NANA MIURA; LESLIE KULIKOWSKI; MAGDA CARNEIRO-SAMPAIO. Investigação Citogenômica de Crianças com Doença Cardíaca Congênita: Experiência de um Centro no Brasil. Arquivos Brasileiros de Cardiologia, v. 118, n. 1, p. 61-67, . (14/50489-9)
NOVAK, E. M.; HALLEY, N. S.; GIMENEZ, T. M.; RANGEL-SANTOS, A.; AZAMBUJA, A. M. P.; BRUMATTI, M.; PEREIRA, P. L.; VINCE, C. S. C.; GIORGI, R. R.; BENDITE, I.; et al. BLM germline and somatic PKMYT1 and AHCY mutations: Genetic variations beyond MYCN and prognosis in neuroblastoma. Medical Hypotheses, v. 97, p. 22-25, . (14/13389-6, 14/50489-9)
CARNEIRO-SAMPAIO, MAGDA; MOREIRA-FILHO, CARLOS ALBERTO; BANDO, SILVIA YUMI; DEMENGEOT, JOCELYNE; COUTINHO, ANTONIO. Intrauterine IPEX. FRONTIERS IN PEDIATRICS, v. 8, . (15/22308-2, 14/50489-9)
LIPHAUS, BERNADETE L.; CARAMALHO, IRIS; RANGEL-SANTOS, ANDREIA; SILVA, CLOVIS A.; DEMENGEOT, JOCELYNE; SALLES CARNEIRO-SAMPAIO, MAGDA MARIA. LRBA deficiency: a new genetic cause of monogenic lupus. ANNALS OF THE RHEUMATIC DISEASES, v. 79, n. 3, p. 427-428, . (14/14880-5, 12/22997-4, 08/58238-4, 14/50489-9)
SOARES, DIOGO C.; DANTAS, ANELISA G.; MATTA, MARINA C.; PASTORINO, ANTONIO C.; MELARAGNO, MARIA ISABEL; KULIKOWSKI, LESLIE; MONTENEGRO, MARILIA; KIM, CHONG A.; CARNEIRO-SAMPAIO, MAGDA; TORRES, LEURIDAN C.. Lymphoproliferative disorder with polyautoimmunity and hypogammaglobulinemia: An unusual presentation of 22q11.2 deletion syndrome. Clinical Immunology, v. 220, . (14/50489-9, 14/11572-8)
YINGYING ZHENG; SIMONE CORREA-SILVA; PATRICIA PALMEIRA; MAGDA CARNEIRO-SAMPAIO. Maternal vaccination as an additional approach to improve the protection of the nursling: Anti-infective properties of breast milk. Clinics, v. 77, . (14/50489-9)
OSHIRO, TELMA MIYUKI; DA SILVA, LAIS TEODORO; ORTEGA, MARINA MAZZILLI; PERAZZIO, SANDRO FELIX; DA SILVA DUARTE, ALBERTO JOSE; CARNEIRO-SAMPAIO, MAGDA. Patient with agammaglobulinemia produces anti-SARS-CoV-2 reactive T-cells after CoronaVac vaccine. Clinics, v. 77, p. 2-pg., . (16/25212-9, 14/50489-9, 18/12460-0)
DOLHNIKOFF, MARISA; FERRANTI, JULIANA FERREIRA; DE ALMEIDA MONTEIRO, RENATA APARECIDA; DUARTE-NETO, AMARO NUNES; GOMES-GOUVEA, MICHELE SOARES; DEGASPARE, NATALIA VIU; DELGADO, ARTUR FIGUEIREDO; FIORITA, CAROLINA MONTANARI; LEAL, GABRIELA NUNES; RODRIGUES, REGINA MARIA; et al. SARS-CoV-2 in cardiac tissue of a child with COVID-19-related multisystem inflammatory syndrome. LANCET CHILD & ADOLESCENT HEALTH, v. 4, n. 10, p. 5-pg., . (14/50489-9)
PERAZZIO, SANDRO FELIX; PALMEIRA, PATRICIA; MORAES-VASCONCELOS, DEWTON; RANGEL-SANTOS, ANDREIA; DE OLIVEIRA, JOAO BOSCO; ANDRADE, LUIS EDUARDO COELHO; CARNEIRO-SAMPAIO, MAGDA. A Critical Review on the Standardization and Quality Assessment of Nonfunctional Laboratory Tests Frequently Used to Identify Inborn Errors of Immunity. FRONTIERS IN IMMUNOLOGY, v. 12, p. 25-pg., . (14/50489-9)
CAVALCANTI, NARA VASCONCELOS; PALMEIRA, PATRICIA; JATENE, MARCELO BISCEGLI; DE BARROS DORNA, MAYRA; CARNEIRO-SAMPAIO, MAGDA. Early Thymectomy Is Associated With Long-Term Impairment of the Immune System: A Systematic Review. FRONTIERS IN IMMUNOLOGY, v. 12, . (14/50489-9)
DA SILVA, LAIS TEODORO; ORTEGA, MARINA MAZZILLI; PERAZZIO, SANDRO FELIX; OSHIRO, TELMA MIYUKI; DA SILVA DUARTE, ALBERTO JOSE; CARNEIRO-SAMPAIO, MAGDA. Anti-SARS-CoV-2 reactive T cells in a XLA patient after CoronaVac vaccine. JOURNAL OF CLINICAL IMMUNOLOGY, v. 42, n. SUPPL 1, p. 2-pg., . (16/25212-9, 14/50489-9)
PALMEIRA, PATRICIA; BARBUTO, JOSE PRIME ALEXANDRE M.; SILVA, CLOVIS ARTUR A.; CARNEIRO-SAMPAIO, MAGDA. Why is SARS-CoV-2 infection milder among children?. Clinics, v. 75, p. 5-pg., . (15/03756-4, 14/50489-9)
SOARES, DIOGO C.; PIAZZON, FLAVIA B.; ZANARDO, EVELIN; PASTORINO, ANTONIO CARLOS; KULIKOWSKI, LESLIE D.; BERTOLA, DEBORA R.; CARNEIRO-SAMPAIO, MAGDA; KIM, CHONG AE. 16q24 DUPLICATION AND IVEMARK SYNDROME: A NOVEL GENOMIC CAUSE?. JOURNAL OF CLINICAL IMMUNOLOGY, v. 37, n. 2, p. 2-pg., . (14/50489-9)
BANDO, SILVIA Y.; BERTONHA, FERNANDA B.; OLIVEIRA, LUCILA H. B.; MOREIRA-FILHO, CARLOS ALBERTO; CARNEIRO-SAMPAIO, MAGDA. Sexual Dimorphism and AIRE-AIRE Interactors-miRNA Coexpression Networks in the Infant Human Thymus. JOURNAL OF CLINICAL IMMUNOLOGY, v. 39, p. 1-pg., . (14/50489-9)
MOREIRA-FILHO, CARLOS ALBERTO; BANDO, SILVIA YUMI; BERTONHA, FERNANDA BERNARDI; SILVA, FILIPI NASCIMENTO; COSTA, LUCIANO DA FONTOURA; FERREIRA, LEANDRO RODRIGUES; FURLANETTO, GLAUCIO; CHACUR, PAULO; NOGUEIRA ZERBINI, MARIA CLAUDIA; CARNEIRO-SAMPAIO, MAGDA. Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants. ONCOTARGET, v. 7, n. 7, p. 7497-7533, . (08/58238-4, 14/50489-9, 05/00587-5, 11/50761-2, 09/53443-1)
GRASSI, MARCILIA SIERRO; MONTENEGRO, MARILIA; ZANARDO, EVELIN ALINE; PASTORINO, ANTONIO CARLOS; DORNA, MAYRA BARROS; KIM, CHONG; JATENE, MARCELO; MIURA, NANA; KULIKOWSKI, LESLIE; CARNEIRO-SAMPAIO, MAGDA. ytogenomics Investigation of Infants with Congenital Heart Disease: Experience of a Brazilian Cente. Arquivos Brasileiros de Cardiologia, v. 118, n. 1, p. 61-67, . (14/50489-9)
MOREIRA-FILHO, CARLOS ALBERTO; BANDO, SILVIA YUMI; BERTONHA, FERNANDA BERNARDI; FERREIRA, LEANDRO RODRIGUES; VINHAS, CHRISTIANA DE FREITAS; BOURGUIGNON OLIVEIRA, LUCILA HABIB; NOGUEIRA ZERBINI, MARIA CLAUDIA; FURLANETTO, GLAUCIO; CHACCUR, PAULO; CARNEIRO-SAMPAIO, MAGDA. Minipuberty and Sexual Dimorphism in the Infant Human Thymus. SCIENTIFIC REPORTS, v. 8, . (15/22308-2, 14/50489-9)
BRAIAN L.A. SOUSA; MAGDA SAMPAIO-CARNEIRO; WERTHER B. DE CARVALHO; CLOVIS A. SILVA; ALEXANDRE A. FERRARO. Differences among Severe Cases of Sars-CoV-2, Influenza, and Other Respiratory Viral Infections in Pediatric Patients: Symptoms, Outcomes and Preexisting Comorbidities. Clinics, v. 75, . (15/03756-4, 14/50489-9)
LEVY, A.; RANGEL-SANTOS, A.; TORRES, L. C.; SILVEIRA-ABREU, G.; AGENA, F.; CARNEIRO-SAMPAIO, M.. T cell receptor excision circles as a tool for evaluating thymic function in young children. Brazilian Journal of Medical and Biological Research, v. 52, n. 7, . (14/50489-9)
SANTANA-SANTOS, DENIS; LIPHAUS, BERNADETE L.; BEATRICE, JULIA M.; CARNEIRO, JORGE D. A.; CARNEIRO-SAMPAIO, MAGDA M. S.; RANGEL-SANTOS, ANDREIA. Low T-cell receptor excision circles (TREC) in children and adolescents with immune thrombocytopenia. British Journal of Haematology, v. 192, n. 4, . (14/50489-9, 08/58238-4)
ORTEGA, MARINA MAZZILLI; DA SILVA, LAIS TEODORO; CANDIDO, ERIKA DONIZETTI; ZHENG, YINGYING; TIYO, BRUNA TIAKI; FERREIRA, ARTHUR EDUARDO FERNANDES; CORREA-SILVA, SIMONE; SCAGION, GUILHERME PEREIRA; LEAL, FABYANO BRUNO; CHALUP, VANESSA NASCIMENTO; et al. Salivary, serological, and cellular immune response to the CoronaVac vaccine in health care workers with or without previous COVID-19. SCIENTIFIC REPORTS, v. 12, n. 1, p. 12-pg., . (18/12460-0, 16/25212-9, 21/06139-7, 19/24849-1, 20/06409-1, 14/50489-9)
VALDENISE MARTINS LAURINDO TUMA CALIL; PATRICIA PALMEIRA; YINGYING ZHENG; VERA LÚCIA JORNADA KREBS; WERTHER BRUNOW DE CARVALHO; MAGDA CARNEIRO-SAMPAIO. CoronaVac can induce the production of anti-SARS-CoV-2 IgA antibodies in human milk. Clinics, v. 76, . (14/50489-9)
GONCALVES, GUILHERME S.; CORREA-SILVA, SIMONE; ZHENG, YINGYING; AVELAR, ISABELA; MONTENEGRO, MARILIA M.; FERREIRA, ARTHUR E. F.; BAIN, VERA; FINK, THAIS T.; SUGUITA, PRISCILA; ASTLEY, CAMILLA; et al. Circulating sTREM-1 as a predictive biomarker of pediatric multisystemic inflammatory syndrome (MIS-C). CYTOKINE, v. 161, p. 12-pg., . (16/06887-5, 21/03037-9, 14/50489-9)
DIAS, A. S.; DAMACENO-RODRIGUES, N. R.; GIMENEZ, T. M.; OLIVEIRA, P. M.; ZERBINI, M. C.; CARNEIRO-SAMPAIO, M.; FILHO, V. ODONE; JATENE, M. B.; VASCONCELOS, D. M.; ROCHA, V.; et al. A model for preservation of thymocyte-depleted thymus. Brazilian Journal of Medical and Biological Research, v. 56, p. 8-pg., . (13/02162-8, 14/50489-9)

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