DEWTON DE MORAES VASCONCELOS
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
43 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 43
- Lomentospora prolificans fungemia in hematopoietic stem cell transplant patients: First report in South America and literature review(2018) PENTEADO, Fernando D.; LITVINOV, Nadia; SZTAJNBOK, Jaques; THOMAZ, Danilo Y.; SANTOS, Antonio M. dos; VASCONCELOS, Dewton M.; MOTTA, Adriana L.; ROSSI, Flavia; FERNANDES, Juliana F.; MARQUES, Heloisa Helena S.; BENARD, Gil; ALMEIDA JR., Joao N. deLomentospora prolificans is a filamentous fungus and an emerging pathogen in immunocompromised patients. It is encountered most commonly in Australia, Spain, and USA. We described the first case of Lomentospora prolificans fungemia in South America. The patient was a hematopoietic stem cell transplantation (HSCT) recipient who developed the infection 37days after stem cells infusion. In addition, we performed a literature review of invasive lomentosporiosis in HSCT patients.
- Disruption of an antimycobacterial circuit between dendritic and helper T cells in human SPPL2a deficiency(2018) KONG, Xiao-Fei; MARTINEZ-BARRICARTE, Ruben; KENNEDY, James; MELE, Federico; LAZAROV, Tomi; DEENICK, Elissa K.; MA, Cindy S.; BRETON, Gaelle; LUCERO, Kimberly B.; LANGLAIS, David; BOUSFIHA, Aziz; AYTEKIN, Caner; MARKLE, Janet; TROUILLET, Celine; JABOT-HANIN, Fabienne; ARLEHAMN, Cecilia S. Lindestam; RAO, Geetha; PICARD, Capucine; LASSEAU, Theo; LATORRE, Daniela; HAMBLETON, Sophie; DESWARTE, Caroline; ITAN, Yuval; ABARCA, Katia; MORAES-VASCONCELOS, Dewton; AILAL, Fatima; IKINCIOGULLARI, Aydan; DOGU, Figen; BENHSAIEN, Ibtihal; SETTE, Alessandro; ABEL, Laurent; BOISSON-DUPUIS, Stephanie; SCHROEDER, Bernd; NUSSENZWEIG, Michel C.; LIU, Kang; GEISSMANN, Frederic; TANGYE, Stuart G.; GROS, Philippe; SALLUSTO, Federica; BUSTAMANTE, Jacinta; CASANOVA, Jean-LaurentHuman inborn errors of IFN-gamma immunity underlie mycobacterial diseases. We describe patients with Mycobacterium bovis (BCG) disease who are homozygous for loss-of-function mutations of SPPL2A. This gene encodes a transmembrane protease that degrades the N-terminal fragment (NTF) of CD74 (HLA invariant chain) in antigen-presenting cells. The CD74 NTF therefore accumulates in the HLA class II+ myeloid and lymphoid cells of SPPL2a-deficient patients. This toxic fragment selectively depletes IL-12-and IL-23-producing CD1c(+) conventional dendritic cells (cDC2s) and their circulating progenitors. Moreover, SPPL2a-deficient memory T(H)1(star) cells selectively fail to produce IFN-gamma when stimulated with mycobacterial antigens in vitro. Finally, Sppl2a(-/-) mice lack cDC2s, have CD4(+) T cells that produce small amounts of IFN-gamma after BCG infection, and are highly susceptible to infection with BCG or Mycobacterium tuberculosis. These findings suggest that inherited SPPL2a deficiency in humans underlies mycobacterial disease by decreasing the numbers of cDC2s and impairing IFN-gamma production by mycobacterium-specific memory T(H)1(star) cells.
- Case report of myeloperoxidase deficiency associated with disseminated paracoccidioidomycosis and peritoneal tuberculosis(2017) DOMINGUES-FERREIRA, Mauricio; LEVY, Ariel; BARROS, Noac Chuffi; BERTOLINI, Dalton Luis; VASCONCELOS, Dewton de MoraesMyeloperoxidase (MOP) is present in monocyte and neutrophil lysosomes, catalyzing hydrogen peroxide and chloride ion conversion to hypochlorous acid. MOP seems to destroy pathogens during phagocytosis by neutrophils and is considered an important defense against innumerous bacteria. We present a patient who had MOP deficiency, who presented with a subacute form of paracoccidioidomycosis and later with peritoneal tuberculosis. MOP deficiency leads to the diminished destruction of phagocytized pathogens. This case gives important evidence of an association between MOP deficiency and increased susceptibility to infection by Paracoccidioides brasiliensis and Mycobacterium tuberculosis.
- Chronic mucocutaneous candidiasis associated with paracoccidioidomycosis in a patient with mannose receptor deficiency: First case reported in the literature(2021) VASCONCELOS, Dewton de Moraes; BERTOLINI, Dalton Luis; FERREIRA, Mauricio DominguesWe describe the first report of a patient with chronic mucocutaneous candidiasis associated with disseminated and recurrent paracoccidioidomycosis. The investigation demonstrated that the patient had a mannose receptor deficiency, which would explain the patient's susceptibility to chronic infection by Candida spp. and systemic infection by paracoccidioidomycosis. Mannose receptors are responsible for an important link between macrophages and fungal cells during phagocytosis. Deficiency of this receptor could explain the susceptibility to both fungal species, suggesting the impediment of the phagocytosis of these fungi in our patient.
- Chronic mucocutaneous candidiasis and systemic lupus erythematosus: a new variant of chronic mucocutaneous candidiasis?(2012) MORAES-VASCONCELOS, Dewton de; DOMINGUES-FERREIRA, Mauricio; PIERI, Patricia de Campos; DUARTE, Alberto Jose da SilvaChronic mucocutaneous candidiasis (CMC) is characterized by susceptibility to Candida infection of skin, nails, and mucous membranes. Autoimmune endocrinopathies are common in CMC patients, but there are no reports of the involvement of systemic autoimmune disorders. We present here the first case of this kind of association in a patient with an autosomal dominant variant of CMC. The individual had had this disorder since childhood and systemic lupus erythematosus with secondary antiphospholipid syndrome, as well as renal, articular and hepatic manifestations without thymoma.
- CD18 deficiency evolving to megakaryocytic (M7) acute myeloid leukemia: Case report(2014) VASCONCELOS, Dewton de Moraes; BEITLER, Beatriz; MARTINEZ, Gracia A.; PEREIRA, Juliana; AMIGO FILHO, Jose Ulysses; KLAUTAU, Giselle Burlamaqui; LIAN, Yu Cheng; NEGRA, Marinella Della; DUARTE, Alberto Jose da SilvaLeukocyte adhesion deficiency type 1 (LAD 1 - CD18 deficiency) is a rare disease characterized by disturbance of phagocyte function associated with less severe cellular and humoral dysfunction. The main features are bacterial and fungal infections predominantly in the skin and mucosal surfaces, impaired wound healing and delayed umbilical cord separation. The infections are indolent, necrotic and recurrent. In contrast to the striking difficulties in defense against bacterial and fungal microorganisms, LAD 1 patients do not exhibit susceptibility to viral infections and neoplasias. The severity of clinical manifestations is directly related to the degree of CD18 deficiency. Here, a 20 year-old female presenting a partial CD18 deficiency that developed a megakaryocytic (M7) acute myeloid leukemia is described for the first time. The clinical features of the patient included relapsing oral thrush due to Candida, cutaneous infections and upper and lower respiratory tract infections, followed by a locally severe necrotic genital herpetic lesion. The patient's clinical features improved for a period of approximately two years, followed by severe bacterial infections. At that time, the investigation showed a megakaryocytic acute myeloid leukemia, treated with MEC without clinical improvement. The highly aggressive evolution of the leukemia in this patient suggests that adhesion molecules could be involved in the protection against the spread of neoplastic cells. (C) 2014 Published by Elsevier Inc.
- Cellular immunodeficiency related to chronic dermatophytosis in a patient with Schistosoma mansoni infection: can schistosomiasis induce immunodeficiency?(2017) FERREIRA, Mauricio Domingues; COLLANIERE, Anna Cristina; BERTOLINI, Dalton Luis; BARROS, Noac Chuffi; VASCONCELOS, Dewton de MoraesHere, we describe a case of hepatosplenic schistosomiasis that progressed to widespread persistent dermatophytosis. Significant T and B lymphocytopenia was confirmed. T-cell deficit is associated with increased susceptibility to fungal infections of skin and mucous membranes. The accumulation of a large amount of blood cells in the spleen could have played a crucial role in the development of lymphocytopenia in the present case. Alternatively, the schistosomiasis-induced increase in prostaglandin E2 levels could have inhibited the production of interferon-gamma, a cytokine fundamental to fungal resistance. This case shows the potential of hepatosplenic schistosomiasis to impair the immune response.
- A model for preservation of thymocyte-depleted thymus(2023) 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.; NOVAK, E. M.DiGeorge syndrome is a disorder caused by a microdeletion on the long arm of chromosome 22. Approximately 1% of patients diagnosed with DiGeorge syndrome may have an absence of a functional thymus, which characterizes the complete form of the syndrome. These patients require urgent treatment to reconstitute T cell immunity. Thymus transplantation is a promising investigational procedure for reconstitution of thymic function in infants with congenital athymia. Here, we demonstrate a possible optimization of the preparation of thymus slices for transplantation through prior depletion of thymocytes and leukocyte cell lineages followed by cryopreservation with cryoprotective media (5% dextran FP 40, 5% Me2SO, and 5% FBS) while preserving tissue architecture. Thymus fragments were stored in liquid nitrogen at -196 & DEG;C for 30 days or one year. The tissue architecture of the fragments was preserved, including the distinction between medullary thymic epithelial cells (TECs), cortical TECs, and Hassall bodies. Moreover, depleted thymus fragments cryopreserved for one year were recolonized by intrathymic injections of 3 x 106 thymocytes per mL, demonstrating the capability of these fragments to support T cell development. Thus, this technique opens up the possibility of freezing and storing large volumes of thymus tissue for immediate transplantation into patients with DiGeorge syndrome or atypical (Omenn-like) phenotype.
- Autoimmune regulator (AIRE) contributes to Dectin-1-induced TNF-alpha production and complexes with caspase recruitment domain-containing protein 9 (CARD9), spleen tyrosine kinase (Syk), and Dectin-1(2012) PEDROZA, Luis A.; KUMAR, Vipul; SANBORN, Keri B.; MACE, Emily M.; NIINIKOSKI, Harri; NADEAU, Kari; VASCONCELOS, Dewton de Moraes; PEREZ, Elena; JYONOUCHI, Soma; JYONOUCHI, Harumi; BANERJEE, Pinaki P.; RUUSKANEN, Olli; CONDINO-NETO, Antonio; ORANGE, Jordan S.Background: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a complex immunologic disease caused by mutation of the autoimmune regulator (AIRE) gene. Autoimmunity in patients with APECED syndrome has been shown to result from deficiency of AIRE function in transcriptional regulation of thymic peripheral tissue antigens, which leads to defective T-cell negative selection. Candidal susceptibility in patients with APECED syndrome is thought to result from aberrant adaptive immunity. Objective: To determine whether AIRE could function in anticandidal innate immune signaling, we investigated an extrathymic role for AIRE in the immune recognition of beta-glucan through the Dectin-1 pathway, which is required for defense against Candida species. Methods: Innate immune signaling through the Dectin-1 pathway was assessed in both PBMCs from patients with APECED syndrome and a monocytic cell line. Subcellular localization of AIRE was assessed by using confocal microscopy. Results: PBMCs from patients with APECED syndrome had reduced TNF-alpha responses after Dectin-1 ligation but in part used a Raf-1-mediated pathway to preserve function. In the THP-1 human monocytic cell line, reducing AIRE expression resulted in significantly decreased TNF-a release after Dectin-1 ligation. AIRE formed a transient complex with the known Dectin-1 pathway components phosphorylated spleen tyrosine kinase and caspase recruitment domain-containing protein 9 after receptor ligation and localized with Dectin-1 at the cell membrane. Conclusion: AIRE can participate in the Dectin-1 signaling pathway, indicating a novel extrathymic role for AIRE and a defect that likely contributes to fungal susceptibility in patients with APECED syndrome. (J Allergy Clin Immunol 2012;129:464-72.)
- A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)(2023) MELO, Adriana; CARVALHO, Luciana Martins de; FERRIANI, Virginia Paes Leme; CAVALCANTI, Andre; APPENZELLER, Simone; OLIVEIRA, Valeria Rossato; NETO, Herberto Chong; ROSARIO, Nelson Augusto; POSWAR, Fabiano de Oliveira; GUIMARAES, Matheus Xavier; KOKRON, Cristina Maria; MAIA, Rayana Elias; SILVA, Guilherme Diogo; KELLER, Gabriel; FERREIRA, Mauricio Domingues; VASCONCELOS, Dewton Moraes; TOLEDO-BARROS, Myrthes Anna Maragna; BARROS, Samar Freschi; NETO, Nilton Salles Rosa; KRIEGER, Marta Helena; KALIL, Jorge; MENDONCA, Leonardo OliveiraIntroductionThe deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil.Patients and methodsThis is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, Sao Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected.ResultsEighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of Sao Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses.ConclusionThe low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).