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1.
Cir. pediátr ; 33(2): 84-90, abr. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-190847

RESUMO

Objetivo: Comprobar la existencia de linfocitos T que incluyen linfocitos infiltrantes de tumor (TILs) en la sangre periférica (SP) de un modelo preclínico de neuroblastoma. Material y métodos: Utilizamos un modelo en ratones inmunodeficientes y otro en inmunocompetentes mediante inyección de suspensiones de la línea tumoral NB36769 con mutación de MYCN (TH-MYCN+). Se realizaron análisis por citometría de flujo (bazo, SP y tumor) y secuenciación del TCR-b en el ADN de muestras pareadas de tumor y SP. Resultados: En los ratones inmunodeficientes el componente principal en SP fue CD4: 83,1% (control) y 86,1% (tumor), siendo PD-1+ el 0,4 y el 0,3%. En el bazo obtuvimos un mayor porcentaje de linfocitos T PD-1+ que en SP, siendo similar en el control (6,5%) y en el ratón con tumor (6,2%), en subpoblación CD4+ exclusivamente. En los ratones inmunocompetentes observamos que la proporción de los 10 clones más frecuentes en los tumores constituía el 11,09% ± 2,83% del repertorio del TCR, mientras en SP representaba el 1,59% ± 0,59% (p = 0,024). Estos resultados sugieren un enriquecimiento de clonotipos dentro del tumor. De los 10 clones más frecuentes en las muestras tumorales, localizamos 9 también en la SP en dos ratones y 6 en el tercero. Además, encontramos secuencias compartidas por TILs de animales diferentes. Conclusiones: Nuestros resultados de inmunofenotipo y clonalidad apuntan a la existencia de linfocitos en SP que podrían contener TILs en un modelo experimental de neuroblastoma


Objective: To detect tumor-infiltrating lymphocytes (TILs) in the peripheral blood (PB) of a preclinical neuroblastoma model. Materials and methods: Two types of preclinical models - immuno-deficient mice and immunocompetent mice - were generated by injecting a cell suspension of neuroblastoma cell line NB36769 with MYCN gene (TH-MYCN+) overexpression. Spleen, tumor, and peripheral blood were studied using flow cytometry to detect PD-1+ T-cells. TCR-b immunose-quencing was performed in matched samples (tumor and peripheral blood). Results: Most PB T-cells of immunodeficient mice were CD4 (control: 83.1%; tumor: 86.1%), with a small proportion of PD-1+ T-cells (control: 0.4%; tumor: 0.3%). However, the percentage of PD-1+T-cells in the spleen was higher (control: 6.5%; tumor: 6.2%), and it was expressed in the CD4+ subset only. Regarding the TCR repertoire of immunocompetent mice, the propor-tion of the 10 most frequent sequences was significantly higher in tumors (11.09% ± 2.83%) than in the peripheral blood (1.59% ± 0.59%) (p = 0.024). These findings are suggestive of clonotype enrichment within the tumor. 9 out of the 10 most frequent tumor clones were identified in the matched peripheral blood sample in 2 mice, and 6 out of 10 in one mouse. In ad-dition, TILs with shared sequences from different animals were found. Conclusions: Our results in terms of immunophenotype and clon-ality suggest the presence of PB T-cells which could include TILs in a preclinical neuroblastoma model


Assuntos
Animais , Camundongos , Neuroblastoma/imunologia , Neuroblastoma/patologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T/imunologia , Modelos Animais de Doenças , Hospedeiro Imunocomprometido , Citometria de Fluxo
2.
Rev. lab. clín ; 12(4): 171-174, oct.-dic. 2019. ilus
Artigo em Espanhol | IBECS | ID: ibc-187315

RESUMO

La leucemia/linfoma de células T del adulto es una neoplasia de linfocitos T causada por el retrovirus humano HTLV-1, con manifestaciones sistémicas y cutáneas muy variables. El HTLV-1 afecta a más de 5-10 millones de personas en el mundo y su distribución geográfica en zonas endémicas se encuentra íntimamente ligada a la prevalencia de leucemia/linfoma de células T del adulto. Existen distintas variantes en función de su presentación clínica siendo las de peor pronóstico la aguda y el linfoma. El diagnóstico diferencial presenta dificultades debido a la inespecificidad de los síntomas. En el laboratorio de análisis clínicos la sospecha diagnóstica es mediante el estudio citológico en sangre periférica con la observación de células características del leucemia/linfoma de células T del adulto


Adult T-cell leukaemia/lymphoma is a mature peripheral T-cell leukaemia of adults associated with infection by the human retrovirus HTLV-1 that presents with highly variable systemic and cutaneous manifestations. HTLV-1 is estimated to affect at least 5-10 million people worldwide, and its geographic distribution in endemic regions is closely related to ATLL prevalence. Adult T-cell leukaemia/lymphoma is classified into different clinical types according to its clinical characteristics, with acute and lymphomatous types having the worst prognosis. Differential diagnosis of adult T-cell leukaemia/lymphoma can be difficult due to the non-specific symptoms in affected individuals. The Clinical Analysis laboratory can help initiate the diagnosis by visualising pathognomonic cells for adult T-cell leukaemia/lymphoma in a peripheral smear


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Linfócitos T/classificação , Análise Química do Sangue/métodos , Antivirais/uso terapêutico
4.
Med. intensiva (Madr., Ed. impr.) ; 43(8): 480-488, nov. 2019. ilus, graf, tab
Artigo em Inglês | IBECS | ID: ibc-185885

RESUMO

Immunotherapy seeks to harness the power of the immune system to eradicate malignant tissues. Despite impressive therapeutic success, however, it can be accompanied by severe adverse effects such as cytokine release syndrome (CRS). These therapies cause the release of a great amount of cytokines, with IL-6 playing a central role, that can potentially lead to multiple organ dysfunction. The diagnosis is based on the presence of compatible clinical symptoms, elevated biomarkers and recent treatment with a biological agent. Mild cases can be managed through symptomatic treatment and fluids, while more severe episodes may need supportive therapy and specific care with the anti-IL-6 receptor monoclonal antibody tocilizumab. Although corticosteroids are also effective, they suppress T-cell activity, and so should only be considered as second line therapy or in cases of severe neurological involvement, since tocilizumab does not cross the blood-brain barrier. Cytokine release syndrome generally has a good prognosis, often being reversible and with a good response to specific treatment. Despite possible concerns about the admission of such patients (mainly with advanced oncological disease), we consider that the Intensive Care Unit should remain an option, since these individuals present a potentially reversible drug-related adverse event and are being treated with a new drug that could change the prognosis of the disorder. Intensive care medicine will become a key component in the management of the complications of modern cancer therapies, dealing with patients presenting an overactive immune system producing organ dysfunction while also trying to maintain treatment efficacy. This is the new paradigm


La inmunoterapia potencia el sistema inmunitario para erradicar las células malignas. A pesar de mostrar un importante éxito terapéutico, puede ir acompañada de efectos adversos graves, como el síndrome de liberación de citocinas. Dichas terapias pueden causar la liberación de importantes cantidades de citocinas, siendo IL-6 el mediador principal, e inducir un cuadro de disfunción multiorgánica. El diagnóstico se basa en la presencia de síntomas clínicos compatibles, elevación de biomarcadores y tratamiento reciente con un agente biológico. Los casos leves se pueden manejar con tratamiento sintomático y fluidoterapia, mientras que los episodios graves necesitarán tratamiento de soporte y específico con tocilizumab, un anticuerpo monoclonal anti-receptor de IL-6. Los corticoides, aunque efectivos, suprimen la actividad de las células T, por lo que su uso se considera de segunda línea o en afectación neurológica grave, ya que tocilizumab no cruza la barrera hematoencefálica. A pesar de que puedan existir dudas sobre el ingreso en unidades de críticos de estos pacientes, principalmente con enfermedad avanzada, consideramos que podrían beneficiarse del ingreso en las UCI, ya que se trata de pacientes con un evento adverso potencialmente reversible, recibiendo un nuevo fármaco que podría cambiar el pronóstico de su enfermedad. La medicina intensiva es clave en el manejo de las complicaciones de las nuevas terapias oncológicas, tratando pacientes con un sistema inmunitario excesivamente activado mientras se intenta preservar la eficacia del tratamiento. Este es el nuevo paradigma


Assuntos
Humanos , Citocinas , Síndrome , Unidades de Terapia Intensiva , Imunoterapia , Prognóstico , Neoplasias/terapia , Biomarcadores , Hidratação/métodos , Neoplasias/fisiopatologia , Linfócitos T/efeitos dos fármacos
5.
Med. clín (Ed. impr.) ; 153(9): 341-346, nov. 2019. ilus, graf, tab
Artigo em Inglês | IBECS | ID: ibc-186266

RESUMO

Introduction and objective: Transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) has been shown to be effective in treating critical limb ischemia (CLI). However, the mechanism of MSCs-mediated improvements, especially on the immune-inflammatory aspects of this disease, is still unknown. In this study, we investigated the changes in T-lymphocyte subpopulations and inflammatory mediators (such as IL-6, IL-10 and TNF-alpha) in PBMCs from CLI patients after UC-MSCs treatment and correlation between inflammatory mediators and EPCs. Patients and methods: 8 patients received UC-MSCs transplantation. Before the treatment, at 24h and 1 month thereafter, peripheral blood samples were collected from 8 patients and 8 healthy volunteers. Patients were evaluated for changes in IL-6, IL-10, TNF-alpha and levels of circulating EPCs. Results: TNF-alpha and IL-6 serum levels increased at 24h (p=0.017, p=0.099) after treatment and then decreased at 1 month (p=0.031, p=0.072) compared with those before treatment. The percentages of CD3+T, CD3+CD4+T-lymphocytes and NK cells decreased significantly after UC-MSCs treatment (p=0.002, p=0.012 and p=0.029, respectively). TNF-alpha (r=−0.602, p=0.038) was shown to be inversely correlated with the number of circulating EPCs. Conclusions: This study demonstrates that UC-MSCs have anti-inflammatory and immunomodulation properties in CLI and suggests that UC-MSCs promote healing of non-healing wounds


Introducción y objetivo: El trasplante de células madre mesenquimales del cordón umbilical (CMM-CU) ha demostrado eficacia en el tratamiento de la isquemia crítica de las extremidades (ICE). Sin embargo, se desconoce el mecanismo de las mejoras mediadas por las CMM, especialmente en los aspectos inmune-inflamatorios de esta enfermedad. Este estudio analiza los cambios en las subpoblaciones de linfocitos T y en los mediadores inflamatorios (como IL-6, IL-10 y TNF-alpha) en CMSP de pacientes con ICE después del tratamiento con CMM-CU y estudia la correlación entre mediadores inflamatorios y células progenitoras endoteliales (CPE). Pacientes y métodos: Ocho pacientes recibieron trasplante de CMM-CU. Se recogieron muestras de sangre periférica de 8 pacientes y 8 voluntarios sanos, antes del tratamiento, a las 24h y un mes después. Los pacientes fueron evaluados para detectar cambios en IL-6, IL-10, TNF-alpha y niveles de CPE circulantes. Resultados: Los niveles séricos de TNF-alpha e IL-6 aumentaron 24h después del tratamiento (p=0,017, p=0,099) y luego disminuyeron al mes (p=0,031, p=0,072) en comparación con los niveles antes del tratamiento. Los porcentajes de CD3+T, CD3+CD4+ linfocitos T y células NK disminuyeron significativamente después del tratamiento con CMM-CU (p=0,002, p=0,012 y p=0,029, respectivamente). TNF-alpha (r=−0,602, p=0,038) demostró estar correlacionada inversamente con el número de CPE circulantes. Conclusiones: Este estudio demuestra que las CMM-CU tienen propiedades antiinflamatorias e inmunomoduladoras en la ICE y sugieren que las CMM-CU promueven la curación de heridas que no cicatrizan


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Isquemia/complicações , Transplante de Células-Tronco Mesenquimais/métodos , Cordão Umbilical/patologia , Células Progenitoras Endoteliais , Índice de Gravidade de Doença , Linfócitos T , Imunomodulação , Doença Arterial Periférica/terapia , Extremidades/patologia , Angiografia
7.
Med. oral patol. oral cir. bucal (Internet) ; 24(4): e555-e561, jul. 2019. graf, ilus
Artigo em Inglês | IBECS | ID: ibc-185670

RESUMO

Background: Nanosecond pulsed electric fields (nsPEFs) showed an inhibitory effect on proliferation of malignant melanoma. In this study, the growth of melanoma were inhibited by changing the systemic immunity. Material and Methods: C57BL/6 mice with B16 malignant were exposed to 200 pulses of 100 ns duration, 30kV/cm. The mice were executed four days later. T lymphocyte has been extracted from spleen. Cell viability was evaluated by CCK-8 assay. CD3+CD4+T cells, CD3+CD8+T cells, regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) were analyzed by flow cytometry. TNF-alfa, IL-2, IL-10, TGF-β, IFN-γ levels in supernatants were assessed by ELISA. Results: C57 malignant melanoma model were established successfully. After the treatment of nsPEFs (30 kV/cm 100 ns 200p), the numbers of T lymphocytes were increased. CD3+CD4+T cells changed from 48% to 51.2%; CD3+CD8+T lymphocytes increased from 39.6% to 40.4%. Treg cells reduced from 4.3% to 2.4%, MDSC decreased by 39.0% to 19.7%. In addition, the level of TNF-α, IL-2 were increased (P < 0.05) and the level of IL-10 were decreased (P < 0.05) and the level of TGF-β and IFN-γ remained stable (P > 0.05). Conclusions: Tumor growth can be effectively inhibited by nsPEFs in vivo, which activate targets of immune respones, accumulation of inflammatory cells and immune cytokines


No disponible


Assuntos
Animais , Camundongos , Melanoma , Neoplasias Cutâneas , Citocinas , Camundongos Endogâmicos C57BL , Linfócitos T
8.
Ars pharm ; 60(2): 65-78, abr.-jun. 2019. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-186009

RESUMO

Two of the most important neglected tropical diseases, Chagas disease and leishmaniasis, are caused by protozoan intracellular parasites of the Trypanosomatida order. These infections provoke a high social burden and lead to the death of a large number of patients. The host triggers several immune mechanisms, but in the absence of adequate treatment, the infection becomes chronic and in many cases causes the appearance of serious alterations. T lymphocytes are fundamental cells of the adaptive system and are the main immune elements that orchestrate the cell-to-cell response in the context of intracellular infections. Furthermore, it has been described that continuous and persistent stimulation in response to pathogenic antigens causes loss of antigen-specific functional capacities in the T cell subsets. This process is known as exhaustion. This review explores the results to date of the exhaustion process during chronic infections caused by the trypanosomatid parasites Leishmania spp. and Trypanosoma cruzi. A large amount of evidence shows upregulation of the markers of the exhaustion process, namely, the inhibitory receptors, during these chronic infections. This increased expression is observed in both the CD4+ and CD8+ T cell populations. In parallel, with this increased expression of inhibitory receptors, the loss of antigen-specific functional capacity of these T cells is detected, reducing the lymphoproliferative potential and the ability to produce protective molecules against these parasitic infections, such as Th1-like cytokines, among others. Additionally, a positive correlation between the high coexpression of these inhibitory molecules and the severity of the pathology is demonstrated. Furthermore, T cell populations experience a phenotypic fluctuation in the course of these infections toward the predominance of effector memory subsets with a late or terminal differentiation state. This balancing in turn affects the functional capacity of the T cells and enriches the number of cells with senescent and apoptotic characteristics. Thus, it has been demonstrated the existence of an exhaustion process that affects key populations for the parasite control. However, the role of this process in the progression of the severity of these pathologies is still unknown. The current drugs used to treat these neglected diseases seem to partially reverse this exhaustion process, denoting a reduction in the high inhibitory receptor expression observed prior to chemotherapies. An improvement in the functional capacity of these T cell populations is also observed, which could be related to the reversion of the dysfunctional process. However, the efforts made to date to evaluate blocking therapies do not lead us to a promising conclusion. It will probably be necessary to test the simultaneous blockade of several pathways and to continue advancing the knowledge to verify their possible use as immunotherapy. It is therefore necessary to continue investigating how this process is triggered and to what extent it influences the appearance of the symptomatology of patients


La enfermedad de Chagas y la leishmaniasis, causadas por parásitos protozoarios intracelulares del orden Trypanosomatida, son consideradas dos de las enfermedades tropicales desatendidas más importantes. Estas infecciones conllevan un alto desgaste social, provocando el deterioro de la salud de un gran número de pacientes e incluso su muerte. Los linfocitos T son células fundamentales del sistema adaptativo y son los principales elementos inmunitarios para el control de estas infecciones intracelulares. La presente revisión explora los estudios y resultados obtenidos hasta la fecha del proceso de agotamiento celular durante las infecciones causadas por los parásitos Leishmania spp. y Trypanosoma cruzi. Así, se recoge que la persistente estimulación celular en respuesta a antígenos de estos patógenos conduce a un proceso de pérdida de la capacidad funcional antígeno-específica en las poblaciones de células T CD4+ y CD8+. Numerosos estudios muestran la existencia de una correlación directa entre el nivel de la co-expresión de receptores inhibitorios y la gravedad de estas patologías. Paralelamente, se detecta la pérdida de la capacidad funcional específica de antígeno de estas células T, lo que reduce su potencial linfoproliferativo y su capacidad de producir moléculas protectoras contra estas infecciones. Además, durante el curso de estas infecciones se observa un incremento de la frecuencia de células T de memoria efectora con un grado de diferenciación tardía o terminal. Este balanceo fenotípico, a su vez, afecta a la capacidad funcional de las células T aumentando el número de células con características senescentes y apoptóticas. Así, los estudios realizados hasta la fecha demuestran con certeza la existencia de un proceso de agotamiento que afecta a poblaciones clave para el control parasitario. Sin embargo, actualmente se desconoce con precisión el papel que este proceso de agotamiento juega en el agravamiento de estas patologías. Los medicamentos actuales usados para tratar estas enfermedades protozoarias revierten parcialmente este proceso de agotamiento. Así, tras el tratamiento, numerosos pacientes muestra una reducción en la expresión de receptores inhibitorios y co-expresión de los mismos. También se ha observado una mejoría en la capacidad funcional de las distintas poblaciones de células T, que podría estar relacionada con la reversión del proceso disfuncional.Sin embargo, los estudios realizados hasta la fecha en la evaluación de terapias de bloqueo de los receptores inhibitorios no han conduci¬do a resultados prometedores. Algunos autores proponen evaluar terapias de bloqueo simultáneo de varias vías de señalización, con el fin de ampliar el conocimiento sobre esta herramienta como posible inmunoterapia de control de la infección por los mencionados parásitos. Además, se considera necesario continuar investigando sobre cómo se desencadena exactamente este proceso de agotamiento celular y en qué medida influye en la aparición de la sintomatología de los pacientes y ausencia de control de la infección


Assuntos
Humanos , Doença de Chagas/imunologia , Leishmaniose/imunologia , Linfócitos T/imunologia , Linfócitos T/parasitologia , Doença Crônica
10.
Med. clín (Ed. impr.) ; 152(9): 346-349, mayo 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-183659

RESUMO

Introduction: Early detection of sepsis is a critical step to improve patient's survival and cellular markers effective diagnosis tools. The aim of this work was to evaluate HLA-DR expression on peripheral T-lymphocytes (CD3+), a marker associate to T-cell activation, as an early sepsis detection tool. Patients and methods: A cross-sectional study was conducted in twenty-six patients with confirmed sepsis by blood culture, eighteen healthy individuals and four patients with systemic inflammatory response syndrome. The analysis of the HLA-DR expression was carried by flow cytometry. Results: The patients with confirmed sepsis had significantly higher percentage of CD3+/HLA-DR+ lymphocytes compared with both, patients with SIRS (20.37±9.42 vs. 8.7±2.9; p<0.005) and healthy individuals (20.37±9.42 vs. 6.58±3.89; p<0.005). Moreover, the average amount of HLA-DR expressed was higher when caused by gram-positive than by gram-negative bacterias (216.61±131.35 vs. 135.05±31.82; p=0.041). A ROC curve analysis showed the utility of HLA-DR expression on T-cells to identify patients with sepsis. Discussion: Our results suggest that surface expression of HLA-DR on T-lymphocytes could be an early marker for the presence of sepsis in non-surgical septic patients


Introducción: La detección temprana de la sepsis es un paso crítico para mejorar la supervivencia del paciente. Nuestro objetivo fue evaluar la expresión de HLA-DR en linfocitos T periféricos (CD3+), marcador asociado a la activación de células T, como herramienta de detección temprana de la sepsis. Pacientes y métodos: Se realizó un estudio en 26 pacientes con sepsis confirmada, 18 sanos y 4 con síndrome de respuesta inflamatoria sistémica(SIRS). La expresión de HLA-DR se midió por citometría de flujo. Resultados: Los pacientes con sepsis tenían un porcentaje significativamente mayor de linfocitos CD3+/HLA-DR+ en comparación con los otros grupos, pacientes con SIRS (20,37±9,42 vs. 8,7±2,9; p<0,005) y sanos (20,37±9,42 vs. 6,58±3,89; p<0,005). La cantidad media de HLA-DR fue mayor cuando la sepsis estaba causada por bacterias gram-positivas que por gram-negativas (216,61±131,35 vs. 135,05±31,82; p=0,041). El análisis mediante curva ROC mostró la utilidad de la expresión de HLA-DR en células T para identificar pacientes con sepsis. Discusión: Nuestros resultados sugieren que la expresión de HLA-DR en linfocitos T podría ser un marcador temprano de sepsis en pacientes sépticos no quirúrgicos


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Sepse/sangue , Antígeno HLA-DR1/sangue , Antígeno HLA-DR1/metabolismo , Linfócitos T/metabolismo , Biomarcadores/sangue , Estudos Transversais , Estudos de Casos e Controles
11.
Allergol. immunopatol ; 47(2): 141-151, mar.-abr. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-180802

RESUMO

Background: The del22q11 syndrome patients present immunological abnormalities associated to thymus alterations. Up to 75% of them present cardiopathies and thymus is frequently removed during surgery. The thymectomy per se has a deleterious effect concerning lymphocyte subpopulations, and T cell function. When compared to healthy controls, these patients have higher infections propensity of variable severity. The factors behind these variations are unknown. We compared immunological profiles of del22q11.2 Syndrome patients with and without thymectomy to establish its effect in the immune profile. Methods: Forty-six del22q11.2 syndrome patients from 1 to 16 years old, 19 of them with partial or total thymectomy were included. Heart disease type, heart surgery, infections events and thymus resection were identified. Immunoglobulin levels, flow cytometry for lymphocytes subpopulations and TREC levels were determined, and statistical analyses were performed. Results: The thymectomy group had a lower lymphocyte index, both regarding total cell count and when comparing age-adjusted Z scores. Also, CD3+, CD4+ and CD8+ lower levels were observed in this group, the lowest count in those patients who had undergone thymus resection during the first year of life. Their TREC level median was 23.6/μL vs 16.1 miL in the non-thymus group (p = 0.22). No differences were identified regarding immunoglobulin levels or infection events frequencies over the previous year. Conclusion: Patients with del22q11.2 syndrome subjected to thymus resection present lower lymphocyte and TREC indexes when compared to patients without thymectomy. This situation may be influenced by the age at the surgery and the time elapsed since the procedure


No disponible


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Linfócitos T/fisiologia , Subpopulações de Linfócitos T/fisiologia , Timectomia/métodos , Timo/cirurgia , Cromossomos Humanos Par 22/imunologia , Deleção Cromossômica , Citometria de Fluxo , Receptores de Antígenos de Linfócitos T/genética
12.
Allergol. immunopatol ; 47(1): 38-42, ene.-feb. 2019. graf
Artigo em Inglês | IBECS | ID: ibc-180769

RESUMO

Introduction: Disseminated BCG infections among other complications of Bacillus Calmette-Guérin (BCG) vaccine are rare and have occurred in children with immunodeficiency disorders such as mendelian susceptibility to mycobacterial disease (MSMD) which could be due to defects in some elements of IL-12/IFN-γ axis. MSMD-causing mutations have been identified in 10 genes during the last two decades. Among them, mutations in the IL12Rβ1 and IFN gamma R1 genes constitute about 80% of recorded cases of MSMD syndrome. The aim of this study was to investigate IL-12RBeta1 and IFN- gammaR1 deficiencies in patients with disseminated BCG infection. Methods: This study was performed on 31 children with disseminated BCG infections who referred to children's medical center. Whole blood cell culture was performed in presence of BCG, IL-12 and IFN- gamma stimulators. The supernatants were assayed for IFN-gamma and IL-12p70 by ELISA method. In order to evaluate IL12Rbeta1 and IFN- gammaR1 receptors expression, flow cytometry staining was performed on the patients’ T-cells stimulated with PHA. Results: Flow cytometry staining of 31 Iranian patients with disseminated BCG infections with the average age of 43 months showed lack of the expression of IL-12RBeta1 and IFN- gamma R1 genes in PHA-T-cells of the nine and one patients, respectively in whom the incomplete production of IFN- gamma and IL-12 was reported by ELISA. Among these 10 patients, eight cases had related parents (80%). Conclusion: It is recommended that to avoid BCG complications, screening be performed for MSMD before BCG inoculation in individuals with positive family history of primary immunodeficiency diseases and inhabitants of areas with high frequency of consanguinity


No disponible


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Vacina BCG/imunologia , Síndromes de Imunodeficiência/epidemiologia , Mutação/genética , Infecções por Mycobacterium/epidemiologia , Receptores de Interferon/genética , Interleucina-12/genética , Linfócitos T/imunologia , Células Cultivadas , Predisposição Genética para Doença , Imunização , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Interferon gama/metabolismo , Interleucina-12/metabolismo , Irã (Geográfico)/epidemiologia , Infecções por Mycobacterium/genética , Infecções por Mycobacterium/imunologia
13.
J. investig. allergol. clin. immunol ; 29(4): 287-293, 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-188749

RESUMO

BACKGROUND: T cells play a major role in delayed-type hypersensitivity reactions. Their reactivity can be assessed by measuring the upregulation of the activation marker CD69, followed by assessment of proliferation and cytokine production. The aim of our study was to develop a novel, whole blood-based, quantitative, absolute count activation index (AI) for analysis of CD69 upregulation in various subsets of T cells in nickel-hypersensitive patients and compare it with previously reported approaches. METHODS: The study population comprised 10 patients with nickel allergy and 9 healthy controls. CD69 expression of CD3+, CD3+CD4+, and CD3+CD8+ T cells in heparinized blood was determined with flow cytometry after incubation with nickel sulfate for 48 hours. The absolute count of CD69+ cells was determined using microbeads. Production of the cytokines IL-2, IL-5, IL-13, and IFN-γ was determined after stimulation of peripheral blood mononuclear cells with nickel sulfate for 48 hours. RESULTS: We showed absolute AI to be the most sensitive approach. The index was calculated as the ratio of the absolute count of nickel-stimulated CD69-positive T cells to the absolute count of CD69-positive T cells in nonstimulated blood. This novel quantitative approach was more discriminative than previously reported approaches in which the T-cell CD69 percentage AI and cytokine production are measured. CONCLUSIONS: Our results demonstrated that measuring the absolute CD69 AI is a novel and accurate approach for quantification of antigen-specific T cells in the blood of patients with hypersensitivity reactions to nickel. This approach may be useful for better in vitro assessment of patients with delayed-type hypersensitivity reactions


ANTECEDENTES: Los linfocitos T juegan un papel importante en las reacciones de hipersensibilidad de tipo retardado. Su actividad puede evaluarse midiendo la expresión del marcador de activación CD69, seguido de la proliferación y la producción de citocinas. El objetivo de nuestro estudio ha sido el desarrollar un novedoso análisis cuantitativo del índice de activación absoluto (AI) en sangre completa de la expresión de CD69, en diferentes subconjuntos de linfocitos T, en pacientes con hipersensibilidad al níquel, y compararlo con los métodos existentes. MÉTODOS: Se estudiaron diez pacientes con alergia al níquel y nueve controles sanos. La expresión de CD69 de los linfocitos T CD3+, CD3+CD4+ y CD3+ CD8+ en sangre heparinizada se determinó con citometría de flujo, después de una incubación con sulfato de níquel durante 48 h. El recuento absoluto de células CD69+ se determinó con microesferas. La producción de las citocinas IL-2, IL-5, IL-13 e IFN-γ se cuantificó después de la estimulación de células mononucleares periféricas, durante 48 h, con sulfato de níquel. RESULTADOS: Se demuestra que la determinación del índice AI absoluto es la metodología más sensible. Se calculó como la relación entre el recuento absoluto de linfocitos T CD69-positivos estimulados con níquel y el recuento absoluto de linfocitos T CD69-positivos en sangre no estimulada. Este nuevo enfoque cuantitativo fue más discriminativo que los enfoques publicados previamente en los que se midió el porcentaje de CD69 de linfocitos T y la producción de citocinas. CONCLUSIONES: Nuestros resultados demostraron que la medición del AI absoluto de CD69 es un enfoque nuevo y preciso para cuantificar los linfocitos T específicos de antígeno en la sangre de pacientes con reacciones de hipersensibilidad al níquel. Este enfoque puede ser útil para una mejor evaluación in vitro de los pacientes con reacciones de hipersensibilidad de tipo retardado


Assuntos
Humanos , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Hipersensibilidade Tardia/diagnóstico , Hipersensibilidade Tardia/etiologia , Lectinas Tipo C/metabolismo , Contagem de Linfócitos , Níquel/efeitos adversos , Biomarcadores/sangue , Estudos de Casos e Controles , Citocinas/metabolismo , Imunofenotipagem , Ativação Linfocitária , Linfócitos T/imunologia , Linfócitos T/metabolismo , Alérgenos/imunologia
17.
J. investig. allergol. clin. immunol ; 28(2): 113-125, 2018. tab, graf, ilus
Artigo em Inglês | IBECS | ID: ibc-173570

RESUMO

Background: The pathogenesis of asthma is dependent on the balance between regulatory and effector T cells, which display differential expression of CD25 and CD26. Therefore, alteration of circulating levels of sCD25 and sCD26 during allergic asthma could be conditioned by changes in leukocyte phenotype. Objectives: To analyze expression of CD25 and CD26 on T lymphocytes and their soluble derivatives (sCD25, sCD26) during stable phases of moderate-severe allergic asthma. Methods: Cross-sectional study with 2 adult cohorts of allergic asthmatics. Clinical, anthropometric, pulmonary, hematological, and biochemical parameters were measured. Phenotyping was performed with flow cytometry in both circulating and cultured leukocytes. Dipeptidyl peptidase 4 (DPP4) activity was assayed in culture supernatants. Results: In vitro studies revealed upregulation of CD26 on human T lymphocytes upon activation, especially under TH17-favoring conditions, and a correlation with soluble DPP4 activity (rs=0.641; P<.001). CD26 expression on lymphocytes was higher in asthmatics, while serum sCD26 was lower in women and patients. The latter finding could be associated with an expanded CD25 low/CD26 low /CD127 low subset of effector CD4 + T cells in allergic asthma, with no changes in Treg percentages. However, women showed an increased Teff/Treg ratio, which could explain their greater susceptibility to asthma. Conclusions: Allergic asthma causes an increment in CD25 low CD26Low helper T cells detected in stable stages. These changes are mirrored in serum and should be considered in the light of the downmodulating role of CD26 in major chemokines related to the pathogenesis of asthma such as CCL11 (eotaxin), CCL5 (RANTES), and CXCL12a (SDF-1alfa) (AU)


Introducción: La patogénesis del asma depende del equilibrio entre células T reguladoras y T efectoras, las cuales presentan distintos niveles de CD25 y CD26. Por tanto, la alteración de la concentración de sCD25 y sCD26 durante el asma alérgica podría estar condicionada por cambios en el fenotipo de los leucocitos. Objetivos: Analizar la expresión de CD25 y CD26 en linfocitos T y sus derivados solubles (sCD25 y sCD26) durante asma alérgica moderada-severa y en fases estables. Métodos: Estudio transversal con dos cohortes de adultos con asma alérgica. Se han medido parámetros clínicos, antropométricos, de función pulmonar, hematológicos y bioquímicos. Se ha hecho el fenotipado de leucocitos circulantes y en cultivo mediante citometría de flujo. Se ha analizado la actividad Dipeptidil peptidasa 4 (DPP4) en sobrenadantes de cultivo. Resultados: Los estudios in vitro mostraron un aumento de expresión de CD26 en linfocitos T humanos tras activación, especialmente en condiciones favorables para TH 17, y una correlación con la actividad DPP4 soluble (rs=0,641; p < 0,001). La expresión de CD26 en linfocitos fue mayor en asmáticos, mientras que sCD26 estaba reducido en sueros de mujeres y pacientes. Este último hallazgo podría ser relacionado con la expansión de una subpoblación CD25 low/CD26 low/CD127 low de células T CD4 + efectoras en asma alérgica, sin cambios en los porcentajes de Treg. Sin embargo, las mujeres mostraron un incremento del cociente Tef/Treg, lo cual podría explicar su mayor susceptibilidad al asma. Conclusiones: El asma alérgica causa un incremento de células TH CD25 low CD26 low durante fases no activas. Estos cambios se reflejan en suero y deberían tenerse en cuenta a la luz de la función inhibidora de CD26 sobre quimioquinas importantes relacionadas con la patogénesis del asma, como CCL11 (eotaxina), CCL5 (RANTES) o CXCL12a (SDF-1alfa)


Assuntos
Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Biomarcadores Farmacológicos , Dipeptidil Peptidase 4/análise , Subunidade alfa de Receptor de Interleucina-2/análise , Asma/diagnóstico , Linfócitos T/imunologia , Estudos Transversais , Estudos de Coortes , Citometria de Fluxo/métodos , Quimiocina CCL11 , Quimiocina CCL5 , Quimiocina CXCL12
19.
Cir. pediátr ; 30(4): 211-215, oct. 2017. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-169650

RESUMO

Objetivo. La balanitis xerotica obliterans (BXO) es una enfermedad de etiología incierta, que afecta a piel y mucosa de genitales masculinos de cualquier edad. La incidencia en niños es baja (9-19%) y en adultos se considera una lesión premaligna. El objetivo de este estudio es establecer la incidencia de BXO en nuestro centro y determinar la correlación entre las características clínicas y los hallazgos inmunohistoquímicos (IHQ). Métodos. Cohorte prospectiva de niños ≤14 años con fimosis circuncidados entre 2014-2016. Análisis estadístico de las características clínicas e histológicas e IHQ para valorar la respuesta inflamatoria, presencia de lesiones premalignas y asociaciones microbiológicas. Resultados. Se incluyeron 176 pacientes circuncidados con una edad media de 7 ± 3 años (rango 2-14 años). La sospecha clínica de BXO, 28,4% (n= 50), se confirmó mediante anatomía patológica en 29,5% (n= 52) con muy buena fuerza de concordancia interobservador (κ= 0,81: p<0,01). El 63,5% (n= 33/52) recibieron corticoterapia como tratamiento inicial. El 7,69% (4/52) presentaron estenosis meatal requiriendo dilataciones meatales/uretrales. Los casos de BXO presentaron una respuesta mediada por linfocitos-T: CD3+ (p< 0,01). Conclusiones. BXO es una enfermedad inflamatoria crónica mediada por linfocitos-T con una incidencia mayor a la reportada. La concordancia interobservador entre la sospecha de BXO y la confirmación histológica es muy buena. La elevación de p53 en los pacientes con BXO indica un posible potencial maligno que requiere tratamiento quirúrgico (circuncisión) y un seguimiento adecuado (AU)


Aim. Balanitis xerotica obliterans (BXO) is a disease of the skin and mucosa of male genitals of unknown etiology that may affect children of any age. It has a low incidence (9-19%) and in adults is considered a potential premalignant lesion. The aim of our study is to establish the incidence of BXO in our center and to determine its correlation between the clinical and immunohistochemical (IHC) findings. Methods. Prospective cohort including all children < 14 years with foreskin pathology that required a circumcision between 2014-2016. Statistical analysis of the clinical characteristics, histological and IHC findings searching for inflammatory response, premalignant lesions and microbiological findings. Results. A total of 176 boys with phimosis had circumcision with a mean age of 7 ± 3 years (Range 2-14). Presurgical diagnosis of BXO was suspected in 28.4% (n= 50) whereas the AP confirmed a total of 29.5% (n= 53) with a very good interobserver concordance (κ= 0.81: p < 0.01). Previous treatment with corticoids in BXO was found in 63.5% (n= 33/52). Meatal stenosis was found in 7.69% (n= 4/52) requiring meatal/urethral dilations. Patients with BXO had a T-Lymphocytes CD3+ mediated inflammatory response with a positive correlation between tumor suppressing protein (p53) expression and chronic inflammation. Conclusions. BXO is a chronic inflammatory disease mediated by T-lymphocytes with an incidence greater than previously reported. Surgeons' criterion has a very good concordance with the AP findings. The elevation of p53 in children with BXO may indicate a plausible malignant potential that may require a surgical treatment (circumcision) and an adequate follow-up (AU)


Assuntos
Humanos , Masculino , Pré-Escolar , Criança , Adolescente , Balanite Xerótica Obliterante/epidemiologia , Balanite Xerótica Obliterante/patologia , Imuno-Histoquímica , Balanite Xerótica Obliterante/complicações , Análise Estatística , Circuncisão Masculina/métodos , Proteína Supressora de Tumor p53/análise , Linfócitos T/patologia , Estudos Prospectivos , Estudos Longitudinais , Ciclina D1/análise
20.
Rev. esp. patol ; 50(3): 188-191, jul.-sept. 2017. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-163530

RESUMO

En este trabajo presentamos el caso de una proliferación linfoide atípica constituida por una población de linfocitos T-CD30+, que ocupa los vasos de un granuloma piogénico (hemangioma capilar lobular). Esta población linfoide T (CD4) presenta atipia y alto índice proliferativo, por lo que resulta necesario descartar un linfoma intravascular. Se ha descrito recientemente una proliferación de estas características que puede ser malinterpretada como un linfoma intravascular debido a la atipia y al alto índice mitótico. Los pacientes tienen buen pronóstico y no presentan signos de linfoma. El reordenamiento T resultó nulo, y la paciente continúa asintomática hasta el presente. Nuestro objetivo es presentar esta nueva entidad de carácter reactivo que simula un linfoma, y resaltar la importancia de su reconocimiento en el diagnóstico diferencial de un linfoma intravascular cutáneo (AU)


We report a case of atypical intravascular CD30+ T-cell proliferation in a patient with pyogenic granuloma (Lobular Capillary Hemangioma). The T (CD4) cell population showed cell atypia and a high proliferation index, thus it was necessary to discard an intravascular lymphoma. Cutaneous intravascular lymphoma commonly represents a diffuse large B-cell lymphoma with predominantly intravascular growth, although it could be also represented by intravascular T cell lymphomas. Recently a CD30+ T-cell proliferation was described that could mimic an intravascular T cell lymphoma. In our case TCR rearrangement was null and the patient remained healthy. We report a new case of this benign reactive process and discuss the importance of its differential diagnosis (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Granuloma Piogênico/sangue , Granuloma Piogênico/diagnóstico , Granuloma Piogênico/patologia , Antígeno Ki-1/análise , Linfócitos T/patologia , Proliferação de Células , Hiperplasia/patologia , Imuno-Histoquímica/métodos , Antígenos CD20/análise , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/patologia
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