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1.
Allergol. immunopatol ; 47(4): 372-327, jul.-ago. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-186509

RESUMO

Introduction: Chronic granulomatous disease (CGD) is a disorder of phagocyte function, characterized by pyogenic infections and granuloma formation caused by defects in NADPH oxidase complex activity. Although the effect of CGD mainly reflects the phagocytic compartment, B cell responses are also impaired in patients with CGD. Materials and methods: Flow cytometric analysis was performed on peripheral blood samples from 35 CGD patients age-matched with healthy controls (HC). The target cells of our study were the naive (IgD+/CD27-), memory (IgD-/CD27+), and B1a (CD5+) cells. Immunoglobulins (Igs) were also measured. This study was performed in a Latin American cohort. Results: We found significantly higher levels of naive B cells and B1a cells, but lower levels of memory B cells were found in CGD patients compared to HC. There was no significant difference of cell percentages per inheritance type. Discussion: Our findings suggest that the deficiency of NADPH oxidase components can affect the differentiation of naive B cells to memory B cells. Consequently, memory cells will be low, which also influenced the expression of CD27 in memory B cells and as a result, the percentage of naive cells increases. An altered phenotype of B lymphocytes in CGD patients may contribute to the opportunistic infections and autoimmune disorders that are seen in this disease


No disponible


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Linfócitos B/imunologia , Subpopulações de Linfócitos B/imunologia , Doença Granulomatosa Crônica/imunologia , NADPH Oxidase 2/genética , Separação Celular , Estudos de Coortes , Citometria de Fluxo , Doença Granulomatosa Crônica/genética , Memória Imunológica , México , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
2.
Allergol. immunopatol ; 44(4): 331-340, jul.-ago. 2016. tab, graf
Artigo em Inglês | IBECS | ID: ibc-154435

RESUMO

Background: The objective of this study was to examine the B lymphocyte subsets in primary immunodeficiency that progress with antibody deficiency. Methods: The patients’ naive, memory, class-switched memory and non-switched memory B cells were compared with those of healthy individuals of matching ages using flow cytometry. Results: A total of 67 patients with antibody deficiency and 28 healthy children of matching ages were included in the study. The median age of the patients was six years (min–max: 1-24) and 40 (59.7%) were male. The median age of the healthy controls was again six years (min–max: 1-17) and 12 (42.8%) were male. Patients with common variable immunodeficiency had higher relative counts of naive cells when compared with the control group; however, they were found to have lower relative counts of memory, relative and absolute counts of non-switched and relative counts of switched B lymphocytes (p = 0.001, 0.023, 0.003-0.003, 0.001, respectively). In patients with selective IgA deficiency, similar to patients with common variable immunodeficiency, the relative counts of naive cells were found to be higher, while the relative counts of memory and relative and absolute counts of non-switched B lymphocytes were found to be lower when compared with the control group (p=0.011, 0.032, 0.006-0.009, respectively). Although patients with selective IgM deficiency had higher relative counts of naive B cells when compared with the control group, they had lower relative and absolute counts of non-switched B lymphocytes (p=0.008-0.016). Conclusions: The B lymphocyte subsets of patients with selective IgA deficiency are largely similar to those of patients with common variable immunodeficiency. Both illness groups exhibit low levels of memory B cells (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Síndromes de Imunodeficiência/etiologia , Síndromes de Imunodeficiência/imunologia , Imunoglobulina G/análise , Imunoglobulina G/imunologia , Antígenos de Diferenciação de Linfócitos B/análise , Antígenos de Diferenciação de Linfócitos B/imunologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/análise , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Agamaglobulinemia/etiologia , Agamaglobulinemia/imunologia , Agamaglobulinemia/patologia , Deficiência de IgA/etiologia , Deficiência de IgA/imunologia , Deficiência de IgA/patologia
3.
Allergol. immunopatol ; 42(1): 35-43, ene.-feb. 2014. tab, graf, ilus
Artigo em Inglês | IBECS | ID: ibc-119051

RESUMO

Background and aims: Common variable immunodeficiency (CVID) is a primary antibody deficiency characterised by decreased antibody production and low or normal B-cell numbers. To elucidate the clinical and immunological heterogeneity of CVID, we studied 16 patients diagnosed with CVID. Methods: We analysed B, T and NK cell populations. We also assessed CD27 expression to define B-cell subsets and examined the expression of molecules important in B-cell proliferation and differentiation, such as the transmembrane activator and CALM interactor (TACI), inducible costimulator (ICOS), CD154 and CD40. Results: We observed reduced B and T-cell numbers in CVID patients; this reduction was more pronounced in adults. While one group of patients (group I) showed a significant reduction in CD27+ memory B-cells, another group (group II) of patients exhibited numbers of CD27+ memory B-cells similar to the healthy donor. The frequency of B-cells and T-cells expressing CD40 and ICOS, respectively, was significantly lower in all CVID patients compared with healthy donors. Finally, a correlation between the frequency of CD27+ memory B-cells and clinical features was observed in CVID patients. Conclusion: These results suggest that in some patients, the combined defects in both T and B-cells may account for CVID. Additionally, patients in group I exhibited an increased frequency of pneumonia and chronic diarrhoea (AU)


No disponible


Assuntos
Humanos , Imunodeficiência de Variável Comum/imunologia , Linfócitos B/imunologia , Hipersensibilidade/imunologia , Antígenos CD40/imunologia , Ligante de CD40/imunologia , Células Matadoras Naturais/imunologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia
4.
Clin. transl. oncol. (Print) ; 14(5): 376-381, mayo 2012. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-126912

RESUMO

INTRODUCTION: In patients, a transient decrease in peripheral blood lymphocyte counts was observed following intraperitoneal administration of the trifunctional monoclonal antibody catumaxomab (anti-human EpCAM x anti-human CD3). The aim of this study was to clarify the observed effect in a preclinical mouse model and to analyse the related mechanism of action in vitro. MATERIALS AND METHODS: A related antibody, BiLu (antihuman EpCAM x anti-mouse CD3), was administered to mice and blood leukocytes were analysed. In vitro studies measured activation and cytokine secretion from human peripheral blood mononuclear cells (PBMC). For the analysis of T cell adhesion, PBMC were preincubated with catumaxomab and then co-cultured with human endothelial cells (HUVEC); T cell adhesion was assessed in the presence or absence of endothelial cell preactivation by TNFα. Adherent T cells were determined by flow cytometry. RESULTS: Treatment of mice with BiLu resulted in a dosedependent transient decrease in CD3+ T cells (both CD4+ and CD8+) that returned to the normal range within 48 h. Catumaxomab physiologically activated T cells in vitro (increased CD69 expression) and induced cytokine release (TNFα, IFNγ). TNFα increased expression of adhesion molecules CD54 and CD62E on endothelial cells. Furthermore, catumaxomab dose-dependently enhanced adhesion of T cells to endothelial cells. Adhesion was further increased when endothelial cells were preactivated with TNFα. CONCLUSIONS: Catumaxomab increases adhesion of T cells to endothelial cells due to antibody-mediated activation of T cells and production of T cell cytokines that up-regulate endothelial cell adhesion molecules. These results provide a mechanistic rationale for the transient, reversible decrease in lymphocyte counts observed following catumaxomab administration in patients, which is likely to be due to redistribution of lymphocytes (AU)


Assuntos
Animais , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/administração & dosagem , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/análise , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangue , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/síntese química , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/classificação , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/deficiência , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/toxicidade
5.
Allergol. immunopatol ; 38(6): 327-332, nov.-dic. 2010. tab, graf
Artigo em Inglês | IBECS | ID: ibc-83252

RESUMO

Background: CD27, a lymphocyte specific member of the Tumour Necrosis Factor- Receptor (TNF-R) family is expressed on the majority of peripheral blood T cells. Activation of T cells via TCR/CD3 induces high CD27 surface expression and release of a soluble form (sCD27) of the molecule. sCD27 level increases in patients suffering from a variety of chronic inflammatory diseases. In the present study we aimed to measure both the serum sCD27 levels and CD27 expression on T cells in asthmatic patients, to evaluate the state of this molecule in allergic inflammation. Methods: Forty-three patients with asthma were included in to the study. CD27 molecule expression and soluble form of this molecule were analysed in atopic asthmatic (n:17) and non-atopic asthmatic (n:13) patients receiving inhaled corticosteroid treatment, in asthmatic patients whose treatment ceased at least for 6 months (n:13) and healthy control subjects (n:14). Results: There were no differences in the expression of CD27 molecule on peripheral blood lymphocyte nor in its soluble form sCD27 levels in sera between the atopic asthmatic and non-atopic asthmatic patients receiving ICS treatment, treatment free asthmatic patients and healthy control subjects. Conclusions: Neither the soluble form of CD27 nor its expression on T cells seem to be a reliable marker of atopic or non-atopic asthmatic inflammation


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Asma/diagnóstico , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/análise , Linfócitos T/imunologia , Biomarcadores/análise
6.
An. R. Acad. Farm ; 74(4): 1-16, oct.-dic. 2008. ilus
Artigo em Espanhol | IBECS | ID: ibc-135203

RESUMO

El receptor para antígeno de los linfocitos T (TCR) es un complejo multiproteíco responsable de la activación y regulación de la respuesta inmune adaptativa. Este receptor muestra una gran especificidad y sensibilidad, a la vez que tiene una baja afinidad por su ligando. El ligando del TCR es un complejo formado por el péptido antigénico y una molécula del complejo principal de histocompatibilidad (MHC). Es más, los linfocitos T responden a antígeno en un rango muy amplio de concentraciones. Esto es, los linfocitos T continúan dando una respuesta aumentada a concentraciones de antígeno que exceden en varios órdenes de magnitud la concentración activadora mínima. La estequiometría y organización del TCR en la membrana han estado bajo intenso escrutinio porque pueden ser clave para explicar sus propiedades paradójicas. Esta revisión subraya la existencia de nuevos datos que indican que el TCR se presenta en linfocitos T intactos y en reposo como una mezcla variable de formas monovalentes (con sólo un sitio de unión para el ligando) y formas multivalentes de distinto grado. Estos resultados contrastan con datos anteriores de estequiometría del TCR obtenidos por procedimientos bioquímicos. No obstante, la mayor parte de estas discrepancias pueden deberse al efecto de distintos detergentes en la integridad del receptor. Aquí discutimos un modelo donde los complejos multivalentes del TCR son los responsables de dotar a los linfocitos T de sensibilidad a antígeno porque son activados por bajas concentraciones de antígeno, mientras que los complejos monovalentes son los responsables del amplio rango dinámico (AU)


The T cell antigen receptor (TCR·CD3) is a multi-subunit complex responsible for triggering an adaptive immune response. It shows high specificity and sensitivity while having a low affinity for the ligand. Furthermore, T cells respond to antigen over a wide concentration range. The stoichiometry and architecture of TCR·CD3 in the membrane have been under intense scrutiny because they might be key to explaining its paradoxical properties. This review highlights new evidence that TCR·CD3 is found on intact, unstimulated T cells in monovalent (one ligand-binding site per receptor) as well as in several distinct multivalent forms. This is in contrast to the TCR·CD3 stoichiometries determined by several biochemical means, but these data can be explained by the effects of different detergents on the integrity of the receptor. Here, we discuss a model in which the multivalent receptors are important for the detection of low concentrations of ligand, and therefore confer sensitivity, whereas the co-expressed monovalent TCR·CD3s allow a wide dynamic range (AU)


Assuntos
Humanos , Masculino , Feminino , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/síntese química , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral , Imunoglobulina A/administração & dosagem , Imunoglobulina A/metabolismo , Detergentes/análise , Colesterol/metabolismo , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/classificação , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/farmacologia , Imunoglobulina A/classificação , Imunoglobulina A/farmacologia , Detergentes/química , Colesterol/provisão & distribução
7.
Inmunología (1987) ; 24(2): 224-234, abr.-jun. 2005. ilus
Artigo em Inglês | IBECS | ID: ibc-93304

RESUMO

El receptor de células T (TCR) reconoce péptidos unidos al complejo mayor de histocompatibilidad (MHC) y transmite esta información a la célula T a través de proteínas adaptadoras. Eladaptador LAT (de «Linker for Activation of T cells») es una proteína transmembrana que, una vez fosforilada en sus residuos detirosina, coordina la unión de muchas proteínas implicadas en señalización intracelular, de modo que promueve la formación de complejos multi-moleculares que regulan la activación y maduraciónde las células T. Estudios funcionales y estructurales, tanto in vitro como in vivo, han revelado un papel central de LAT como plataforma de distribución de señales procedentes del TCR y pre-TCR, así como una inesperada función en la regulación del desarrollo y homeostasis de las células T. En esta revisión se discuten algunos de los más recientes avances acerca de las funciones de este adaptador en la maduración y activación de los linfocitos T (AU)


The T Cell Receptor (TCR) recognizes peptides bound to majorhistocompatibility complex (MHC) molecules and relays this information to the T cell through adapter proteins. The adapter LAT(Linker for Activation of T cells) is a transmembrane protein that,once phosphorylated in its tyrosine residues, coordinates the binding of many signaling proteins in order to assemble multi-molecular complexes that regulate T cell activation and maturation.Structure/function studies, both in vitro and in vivo, have revealeda central role of LAT as a platform for the distribution of signalscoming from the TCR and the pre-TCR, and also an unexpectedfunction in the regulation of T cell development and homeostasis.Thus, in the present review we discuss some of the recent advances on the role of this adaptor in T lymphocyte developmentand activation (AU)


Assuntos
Humanos , Receptores de Antígenos de Linfócitos T/imunologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Antígenos de Histocompatibilidade/imunologia
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