Browsing by Author "Fonseca, S."
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- CD56-Negative Aggressive NK Cell Leukemia Relapsing as Multiple Cranial Nerve Palsies: Case Report and Literature ReviewPublication . Guerreiro, M.; Príncipe, F.; Teles, M.; Fonseca, S.; Santos, A.; Fonseca, E.; Gomes, P.; Marques, C.; Lima, M.Aggressive natural killer cell leukemia (ANKL) is extremely rare and habitually manifests as a systemic disease with multiorgan failure that rapidly evolves to death. The neoplastic natural killer (NK) cells usually harbor the Epstein-Barr virus (EBV) with a latent viral infection pattern type II; they often have a cytoplasmic CD3ε+ and surface CD3-, CD2+, and CD56+ immunophenotype, and they show complex genetic abnormalities affecting multiple tumor suppressor genes and oncogenes. We present a rare case of CD56-negative ANKL and review the clinical and laboratorial criteria for the diagnosis, as well as the available therapies.
- Chemokine Receptor Expression on Normal Blood CD56(+) NK-Cells Elucidates Cell Partners That Comigrate during the Innate and Adaptive Immune Responses and Identifies a Transitional NK-Cell PopulationPublication . Lima, M.; Leander, M.; Santos, M.; Santos, A.; Lau, C.; Queirós, M.; Gonçalves, M.; Fonseca, S.; Moura, J.; Teixeira, M.; Orfao, A.Studies of chemokine receptors (CKR) in natural killer- (NK-) cells have already been published, but only a few gave detailed information on its differential expression on blood NK-cell subsets. We report on the expression of the inflammatory and homeostatic CKR on normal blood CD56(+low) CD16(+) and CD56(+high) CD16(-/+low) NK-cells. Conventional CD56(+low) and CD56(+high) NK-cells present in the normal PB do express CKR for inflammatory cytokines, although with different patterns CD56(+low) NK-cells are mainly CXCR1/CXCR2(+) and CXCR3/CCR5(-/+), whereas mostly CD56(+high) NK-cells are CXCR1/CXCR2(-) and CXCR3/CCR5(+). Both NK-cell subsets have variable CXCR4 expression and are CCR4(-) and CCR6(-). The CKR repertoire of the CD56(+low) NK-cells approaches to that of neutrophils, whereas the CKR repertoire of the CD56(+high) NK-cells mimics that of Th1(+) T cells, suggesting that these cells are prepared to migrate into inflamed tissues at different phases of the immune response. In addition, we describe a subpopulation of NK-cells with intermediate levels of CD56 expression, which we named CD56(+int) NK-cells. These NK-cells are CXCR3/CCR5(+), they have intermediate levels of expression of CD16, CD62L, CD94, and CD122, and they are CD57(-) and CD158a(-). In view of their phenotypic features, we hypothesize that they correspond to a transitional stage, between the well-known CD56(+high) and CD56(+low) NK-cells populations.
- CHEMOKINE RECEPTOR REPERTOIRE REFLECTS MATURE T-CELL LYMPHOPROLIFERATIVE DISORDER CLINICAL PRESENTATIONPublication . Moura, J.; Rodrigues, J.; Santos, A.; Teixeira, M.; Queirós, M.; Santos, M.; Gonçalves, M.; Fonseca, S.; Laranjeira, C.; Ribeiro, F.; Acosta, M.; Rodrigues, A.; Júnior, E.; Lima, M.The World Health Organisation classification of mature T-cell lymphoproliferative disorders, combines clinical, morphological and immunophenotypic data. The later majorly contributes for the classification, as well as to the understanding of the malignant T-cell behaviour. The fact that T-cell migration is regulated by chemokines should, in theory, enable us to identify tissue tropism and organ involvement by neoplastic Tcells, through monitoring of chemokine receptor surface expression.
- CONTRIBUTO DA CITOMETRIA DE FLUXO PARA O ESTUDO DOS RETICULÓCITOSPublication . Queirós, M.; Moreira, S.; Leander, M.; Freitas, I.; Cleto, E.; Santos, F.; Henriques, M.; Teixeira, F.; Iglésias, I.; Santos, A.; Santos, M.; Gonçalves, M.; Fonseca, S.; Lau, C.; Bini-Antunes, M.; Teixeira, M.; Pinho, L.; Santos-Silva, A.; Lima, M.Os reticulócitos são eritrócitos jovens cuja presença no sangue periférico (SP) reflecte a actividade eritropoiética da medula óssea. Assim e apesar de, em determinadas situações de stress ou em diversas patologias hematológicas, se poderem encontrar no SP reticulócitos em diferentes estadios de maturação,pouco se sabe acerca deles. Este trabalho teve como objectivo caracterizar fenotipicamente as várias fases de maturação dos reticulócitos por citometria de fluxo (CF).
- CULTURAS CELULARES DE FIBROBLASTOS: FENÓTIPO E ESTUDO DO CICLO CELULAR POR CITOMETRIA DE FLUXOPublication . Fonseca, S.; Leite, F.; Sousa, R.; Santos, A. H.; Lau, C.; Teixeira, M.A.; Queirós, M.L.; Santos, M.; Gonçalves, M.; Porto, B.; Lima, M.
- Expressão dos recetores de quimiocinas, CXCR3 e CCR5, nas células natural killer do sangue de cordão umbilicalPublication . Bini-Antunes, M.; Leander, M.; Rebelo, R.; Benevides, P.; Santos, A.; Rodrigues, J.; Oliveira, L.; Queirós, M.; Santos, M.; Gonçalves, M.; Fonseca, S.; Lau, C.; Teixeira, M.; Lima, M.
- HUMAN BLOOD T AND NK CELL IN VITRO STIMULATION REVEALS A SIMILAR ACTIVATION PHENOTYPE THAT RESEMBLES EARLY ACTIVATION STAGES DURING ACUTE VIRUS INFECTIONPublication . Moura, J.; Gonçalves, M:; Fonseca, S.; Santos, A.; Queirós, M.; Teixeira, M.; Lima, M.The complexity of T and NK-cell responses needs a great deal of control in the way these cells respond to stimulation. This is made by a precise regulation of gene expression leading to specific changes of membrane proteins, in order to acquire their full cytotoxic or immunological mediators secreting potential. The immunophenotypic changes occurring in-vivo on blood T and NK-cells in patients with acute and chronic infections have been previously characterized in detail, defining early and late activation related phenotypes, but in-vitro experiments are needed to define the earliest activation stages.
- IMPORTÂNCIA DA CITOMETRIA DE FLUXO NA AVALIAÇÃO DE LESÕES CEREBRAIS SUSPEITAS DE LINFOMAPublication . Campos, F.; Bini-Antunes, M.; Santos, A.; Queirós, M.; Santos, M.; Gonçalves, M.; Fonseca, S.; Lau, C.; Teixeira, M.; Nunes, P.; Pinheiro, C.; Pires, M.; Lima, M.A citometria de fluxo (CF) tem adquirido um papel cada vez maior no diagnóstico e classificação das patologias linfoproliferativas, sendo fundamental a integração e complementaridade das informações obtidas por citometria com os resultados do estudo anatomo-patológico (EAP). Existem, porém, escassas referências na literatura que documentem a importância da CF na avaliação de lesões cerebrais suspeitas de linfoma.
- Lymphocyte gene expression signatures from patients and mouse models of hereditary hemochromatosis reveal a function of HFE as a negative regulator of CD8+ T-lymphocyte activation and differentiation in vivoPublication . Costa, M.; Cruz, E.; Oliveira, S.; Benes, Vl.; Ivacevic, T.; Silva, M.; Vieira, I.; Dias, F.; Fonseca, S.; Gonçalves, M.; Lima, M.; Leitão, C.; Muckenthaler, M.; Pinto, J.; Porto, G.Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocytes from HH patients selected according to CD8+ T-lymphocyte numbers and from Hfe-/- mice maintained either under normal or high iron diet conditions. In addition, T-lymphocyte apoptosis and cell cycle progression were analyzed by flow cytometry in HH patients. HH patients with low CD8+ T-lymphocyte numbers show a differential expression of genes related to lymphocyte differentiation and maturation namely CCR7, LEF1, ACTN1, NAA50, P2RY8 and FOSL2, whose expression correlates with the relative proportions of naïve, central and effector memory subsets. In addition, expression levels of LEF1 and P2RY8 in memory cells as well as the proportions of CD8+ T cells in G2/M cell cycle phase are significantly different in HH patients compared to controls. Hfe-/- mice do not show alterations in CD8+ T-lymphocyte numbers but differential gene response patterns. We found an increased expression of S100a8 and S100a9 that is most pronounced in high iron diet conditions. Similarly, CD8+ T lymphocytes from HH patients display higher S100a9 expression both at the mRNA and protein level. Altogether, our results support a role for HFE as a negative regulator of CD8+ T-lymphocyte activation. While the activation markers S100a8 and S100a9 are strongly increased in CD8+ T cells from both, Hfe-/- mice and HH patients, a differential profile of genes related to differentiation/maturation of CD8+ T memory cells is evident in HH patients only. This supports the notion that HFE contributes, at least in part, to the generation of low peripheral blood CD8+ T lymphocytes in HH.
- MATURAÇÃO DA LINHA ERITRÓIDE NA MEDULA ÓSSEA POR CITOMETRIA DE FLUXOPublication . Queirós, M. L.; Cerejo, L.; Leander, M.; Freitas, I.; Cleto, E.; Barbot, J.; Gonçalves, M.; Santos, M.; Santos, A.; Fonseca, S.; Lau, C.; Teixeira, M. A.; Pinho, L.; Santos-Silva, A.; Lima, M.MATURAÇÃO DA LINHA ERITRÓIDE NA MEDULA ÓSSEA POR CITOMETRIA DE FLUXO Maria Luís Queirós1,2,3, Liliana Cerejo1,4, Magdalena Leander1,3, Inês Freitas3,5, Esmeralda Cleto3,6, José Barbot3,7, Marta Gonçalves1,3, Marlene Santos1,3, Ana Helena Santos1,3,8, Sónia Fonseca1,3, Catarina Lau1,3, Maria Anjos Teixeira1,3, Luciana Pinho1,3, Alice Santos-Silva2, Margarida Lima1,3,8 1Serviço Hematologia Clínica, Laboratório de Citometria, HSA/CHP; 2Serviço de Bioquímica, FF/UP; 3UMIB/ICBAS/UP; 4Mestrado em Análises Clínicas e Saude Pública, ICS/UCP; 5Serviço de Hematologia Laboratorial, HSA/CHP; 6Serviço de Pediatria, HMP/CHP e HSA/CHP; 7Unidade de Hematologia Pediátrica, HMP/CHP; 8Consórcio Euroflow. Hospital de Santo António, Centro Hospitalar do Porto (HSA/CHP), Porto. Faculdade de Farmácia, Universidade do Porto (FF/UP), Porto. Unidade Multidisciplinar de Investigação Biomédica, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto (UMIB/ICBAS/UP), Porto. Instituto de Ciências da Saúde, Universidade Católica Portuguesa (ICS/UP), Porto. Hospital Maria Pia, Centro Hospitalar do Porto (HSA/CHP), Porto. Consórcio Euroflow. Introdução No processo de maturação dos eritrócitos do sangue (RBC), as células eritróides (ERI) sofrem uma série de mudanças dentro da medula óssea (MO), correspondentes a fases de maturação específicas que são identificadas por microscopia de luz, usando critérios morfológicos e citoquímicos. No entanto, pouco se sabe sobre as alterações imunofenotipicas que caracterizam a maturação ERI normal. Objectivo Caracterizar fenotipicamente as várias fases de maturação da linha eritróide por citometria de fluxo (CF). Material e Métodos Foram estudados por CF 15 aspirados de medula óssea de indivíduos adultos sem doença hematológica. O estudo foi efectuado utilizando o tubo de 8 cores recomendado pelo consórcio Euroflow para o estudo das ERI nas síndromes mielodisplásicos (SMD): anti-CD45 (PO) / anti-HLA-DR (PB) / anti-CD71 (APC-H7) / anti-CD33 (APC) /anti-CD117 (PC7) / anti-CD34 (PERCP Cy5.5) / anti-CD105 (PE) / anti-CD36 (FITC). As amostras foram adquiridas no citómetro NaviosTM (Becman Coulter) e analisadas com o software Infinicyt (Cytognos). Resultados Utilizando este protocolo identificamos 4 estadios imunofenotípicos, um correspondendo às ERI mais imaturas (estadio 1: CD71+CD36+CD105+CD117+CD34+; média de 0.9%; variando de 0.1 a 1.7%) e três estadios subsequentes caracterizados pela perda sequencial de CD34 (estadio 2: CD71+CD36+CD105+CD117+CD34-; 5.6%, 3.4 a 7.6%), CD117 (estadio 3: CD71+CD36+CD105+CD117-CD34-; 32.2%; 15.6 a 49.8%) e CD105 (estadio 4: CD71+CD36+CD105-CD117-CD34-; 61.3%, 41.1 a 78.2%) Discussão O tubo recomendado pelo Euroflow para o estudo das ERI nos SMD permitiu identificar 4 estadios de diferenciação dos RBC, os quais correspondem provavelmente aos quatro estadios que são identificados convencionalmente por critérios morfológicos: estadios 1 - pró-eritroblastos; estadio 2 - eritroblastos basófilos; estadio 3 - eritroblastos policromáticos; e estadio 4 - eritroblastos ortocromáticos. É necessário efectuar mais estudos para caracterizar melhor estas populações, para as comparar com as obtidas por critérios morfológicos e para as utilizar para identificar e monitorizar alterações nas ERI em várias doenças hematológicas primárias e secundárias. Apresentador: Maria Luís Queirós, Técnica Superior de Saúde, Serviço Hematologia Clínica, Laboratório de Citometria, HSA/CHP; Aluna de Doutoramento em Ciências Farmacêuticas, FF/UP.