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Frontiers of Medicine ; (4): 285-294, 2022.
Article in English | WPRIM | ID: wpr-929193


Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive efficacy in treating B-cell malignancies. A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR, a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule, for the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL). Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell (C-CAR011) treatment. The overall response rate was 20% and 50% at 4 and 12 weeks after the infusion of C-CAR011, respectively, and the disease control rate was 60% at 12 weeks after infusion. Treatment-emergent adverse events occurred in all patients. The incidence of cytokine release syndrome in all grades and grade ⩾ 3 was 90% and 0, respectively, which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel. Neurotoxicity or other dose-limiting toxicities was not observed in any dose cohort of C-CAR011 therapy. Antitumor efficacy was apparent across dose cohorts. Therefore, C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL, and further large-scale clinical trials are warranted.

Antigens, CD19/adverse effects , China , Humans , Lymphoma, Large B-Cell, Diffuse/therapy , Receptors, Chimeric Antigen , T-Lymphocytes
Frontiers of Medicine ; (4): 139-149, 2022.
Article in English | WPRIM | ID: wpr-929189


The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.

Antigens, CD19/therapeutic use , Antineoplastic Agents/pharmacology , Humans , Immunotherapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , T-Lymphocytes
Article in English | WPRIM | ID: wpr-928926


OBJECTIVE@#To compare the circular pathological changes of chronic hepatitis B (CHB) patients according to the tongue diagnosis.@*METHODS@#Totally 41 CHB patients with typical white tongue coating (WTC) or yellow tongue coating (YTC) were enrolled and 14 healthy volunteers with normal tongue manifestation served as controls. The mRNA expression of peripheral leukocytes was detected by GeneChips, and 9 genes were randomly selected for expression validation. Circular metabolites were detected by gas chromatographymass spectrometry. Biological information was analyzed based on ingenuity pathways analysis or metabolomics database and the integrated networks were constructed by ClueGO.@*RESULTS@#A total of 945 and 716 differentially expressed genes were found in patients with WTC and YTC relative to healthy volunteers respectively. The biological information analysis indicated that CHB patients had obviously increased functions in cell death, apoptosis and necrosis (Z-score ⩾2, P<0.05) and decreased activation in T lymphocytes (Z-score ⩽-2, P<0.05), regardless of the tongue manifestation. Compared to patients with WTC, the YTC patients were predicted to be more active in functions related to virus replication (Z-score ⩾2, P<0.05), and the content of circular fatty acids, such as oleic acid (P=0.098) and lauric acid (P=0.035), and citric acid cycle-related metabolites were higher in the YTC patients (P<0.1). The integrated analysis based on differential genes and metabolites indicated that the most difference in the biological function network between the WTC and YTC patients was tumor necrosis factor receptor associated factor 6 mediated-nuclear factor kappa-B activation process.@*CONCLUSIONS@#CHB patients with YTC had more severe inflammation and fatty acids metabolism aberrant than patients with WTC. The results facilitate the modern pathological annotation of Chinese medicine tongue diagnosis theory and provide a reference for the interpretation of pharmacological mechanisms of Chinese medicine treatment.

Fatty Acids , Hepatitis B virus/genetics , Hepatitis B, Chronic , Humans , Metabolomics , T-Lymphocytes , Tongue
Article in Chinese | WPRIM | ID: wpr-928661


OBJECTIVE@#To explore the effect and possible mechanism of dimethyl fumarate (DMF) on T-cell acute lymphoblastic leukemia (T-ALL), and provide experimental and theoretical basis for the clinical treatment of T-ALL.@*METHODS@#Jurkat cells were treated with different concentrations of DMF for 24 hours, and then the proportion and absolute count of Ki67-positive Jurkat cells were analyzed by flow cytometry. Meanwhile, the protein levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and E3 ubiquitin ligase HACE1 in Jurkat cells treated with DMF for 24 hours were evaluated by Western blot. Nrf2 proteins were co-immunoprecipitated in Jurkat cells, and then HACE1 protein was assessed by Western blot. Plasmids of Flag-Nrf2 and different gradients of Flag-HACE1 were transfected into HEK293T cells, and the levels of Flag-Nrf2 were detected by Western blot after 48 hours.@*RESULTS@#DMF could significantly inhibit the proportion and absolute count of Ki67-positive Jurkat cells, and DMF inhibited the proliferation of Jurkat cells in a dose-dependent manner (r=0.9595, r=0.9054). DMF could significantly up-regulate the protein levels of Nrf2 and E3 ubiquitin ligase HACE1 in Jurkat cells (P<0.01, P<0.01). HACE1 physically interacted with Nrf2 in Jurkat cells. Overexpression of Flag-HACE1 significantly increased the protein level of Flag-Nrf2 in a dose-dependent manner (r=0.9771).@*CONCLUSION@#DMF inhibits the proliferation of T-cell acute lymphoblastic leukemia cell. The mechanism may be that, DMF significantly up-regulates the protein levels of Nrf2 and E3 ubiquitin ligase HACE1, and HACE1 interacts with Nrf2 and positively regulates Nrf2 protein level.

Dimethyl Fumarate/pharmacology , HEK293 Cells , Humans , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , T-Lymphocytes , Ubiquitin-Protein Ligases
Rev. Rede cuid. saúde ; 15(2): [105-114], dez. 2021.
Article in Portuguese | LILACS | ID: biblio-1349498


A lesão perirradicular consiste em uma doença inflamatória de origem microbiana causada pelo desenvolvimento da infecção no sistema de canais radiculares. Citocinas pró-inflamatórias e imunoregulatórias são fundamentais para o desenvolvimento dessas lesões. No entanto, pouco se sabe sobre como e em que momento elas atuam nas diferentes fases de desenvolvimento da lesão. A presença de bactérias e seus subprodutos metabólicos evocam reações imunológicas do hospedeiro, como a chegada de diferentes células do sistema de defesa aos tecidos periapicais, bem como produção de mediadores inflamatórios. Diversos estudos vêm sendo realizados para identificar os mediadores envolvidos na atividade de reabsorção óssea, permitindo uma melhor compreensão sobre a etiopatogenia das periacopatias. Além disso, investigações prévias sugerem que os linfócitos T CD4+ são as célulasinflamatórias predominantes que se infiltram na patogênese das lesões periapicais e desempenham um papel importante no curso da doença. Células Th17, que compreendem uma subpopulação da T CD4+, cujo produto principal é a interleucina IL-17. A IL-17 é uma citocina pró-inflamatória que exerce efeitos potentes em diferentes tipos celulares da imunidade inata e é considerada uma ponte molecular entre o sistema imunológico inato e adaptativo. Ela também é responsável pelo início e propagação da inflamação, apresentando um papel importante na ligação da ativação da célula T para mobilização e ativação de neutrófilos. Neste contexto, a presente revisão da literatura discutiu o papel da IL-17 na formação e manutenção de lesões perirradiculares.

The periapical lesion is an inflammatory disease of microbial origin caused by infection development in the root canal system. Pro-inflammatory and immunoregulatory cytokines are essential for the development of these lesions. However, little is known about how and when they act in the different stages of injury development. The presence of bacteria and their metabolic products evoke host immune reactions, such as the arrival of different cells of the defense system in periapical tissues, as well as the production of inflammatory mediators. Several studies have been carried out to identify the mediators involved in bone resorption activity, allowing a better understanding of the etiopathogenesis of periapicopathies. In addition, previous investigations suggest that CD4 + T lymphocytes are the predominant inflammatory cells that infiltrate the pathogenesis of periapical lesions and play an important role in the course of the disease. Th17 cells, which comprise a subpopulation of CD4 + T, whose main product is interleukin IL-17. IL-17 is a pro-inflammatory cytokine that has potent effects on different cell types of innate immunity and is considered a molecular bridge between the innate and adaptive immune systems. It is also responsible for the onset and spread of inflammation, playing an important role in linking T cell activation to neutrophil mobilization and activation. In this context, the present literature review discussed the role of IL-17 in the formation and maintenance of periradicular lesions.

Humans , Male , Female , Periapical Abscess , Wounds and Injuries , T-Lymphocytes , Interleukin-17
Hematol., Transfus. Cell Ther. (Impr.) ; 43(4): 396-401, Oct.-Dec. 2021. tab, graf
Article in English | LILACS | ID: biblio-1350809


ABSTRACT CD28 null T helper (Th) cells are rare in healthy individuals, but they are increased in various inflammatory and immune-mediated diseases. In this study, we determined the size of the CD4+/CD28 null T lymphocyte compartment in the peripheral blood of 40 autoimmune hemolytic anemia (AIHA) patients (idiopathic and secondary) and 20 healthy control subjects, using tri-color flow cytometry. The frequency and absolute count of CD4+/CD28 null T helper (Th) cells was significantly higher in idiopathic AIHA patients, compared to healthy controls (p = 0.001 and 0.001, respectively) and to patients with secondary AIHA (p = 0.04 and 0.01, respectively). The percentage of CD4+/CD28 null Th cells was also negatively correlated to the hemoglobin (Hb) level (p = 0.03). These findings demonstrate, for the first time, the expansion of this phenotypically-defined population of T lymphocytes in patients with idiopathic AIHA and indicate that it likely plays an etiological role in the development of this disease. However, establishing the use of this marker for diagnosis or monitoring treatment of such patients needs further studies.

Humans , Male , Female , Adolescent , Adult , Middle Aged , T-Lymphocytes, Helper-Inducer , Anemia, Hemolytic, Autoimmune , T-Lymphocytes , CD4 Antigens , Autoimmunity , CD28 Antigens , Th1 Cells , Flow Cytometry
Infectio ; 25(4): 276-283, oct.-dic. 2021. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1286722


Resumen Objetivo: Describir la supervivencia a siete años y los principales factores asociados a esta, en las personas con VIH que fueron atendidas en el sistema de salud colombiano entre 2011 a 2018. Métodos: Análisis de supervivencia de una cohorte de 64 039 personas diagnosticadas con VIH en Colombia. Se aplicó el método de Kaplan-Meier para estimar la probabilidad de supervivencia a partir de la fecha del diagnóstico. Se ajustó un modelo de supervivencia paramétrico flexible de Royston Parmar. Resultados: La estimación de la supervivencia global a 7 años fue de 94,8% (IC 95%: 94,5-95,2). El mayor riesgo de muerte se presentó en los hombres (HR: 1,2; IC 95%: 1,1-1,4; p: 0,010); en personas ≥50 años de edad (HR: 3,1; IC 95%: 1,6-6,3; p: 0,002); en el régimen subsidiado (HR: 2,2; IC 95%: 1,9-2,5; p: <0,001); en la etapa sida (HR: 2,8; IC 95%: 2,1-3,7; p: <0,001); en quienes presentaron la última carga viral detectable (HR: 7,1; IC 95%: 6,0-8,3; p: <0,001); y en quienes mostraron conteo de linfocitos T CD4+ <350 células/μL (HR: 1,9; IC 95%: 1,4-2,4; p: <0,001). Conclusión: La probabilidad de la supervivencia de las personas que viven con VIH aumenta al ser diagnosticados en edades jóvenes, en quienes presenten un recuento de linfocitos T CD4+ ≥350 células/μL, una carga viral indetectable (< 50 copias/mL) y no se encuentren en etapa sida.

Summary Objective: to describe the seven-year survival and predictors of mortality among people with HIV who were treated in the Colombian health system between 2011 and 2018. Methods: 64 039 people diagnosed with HIV in Colombia were included. Kaplan-Meier analysis estimated the probability of survival from the date of diagnosis. A Royston Parmar flexible parametric survival model was fitted. Results: The overall survival at 7 years was 94.8% (95% CI: 94.5-95.2). Survival was related to sex (men, HR: 1.2; 95% CI: 1.1-1.4; p: 0.010); people ≥50 years of age (HR: 3.1; 95% CI: 1.6-6.3; p: 0.002); subsidized regime (HR: 2.2; 95% CI: 1.9-2.5; p: <0.001); AIDS stage (HR: 2.8; 95% CI: 2.1-3.7; p: <0.001); a detectable viral load (HR: 7.1; 95% CI: 6.0-8.3; p: <0.001); and a CD4+ Lymphocyte count <350 cells/μL (HR: 1.9; 95% CI: 1.4-2.4; p: <0.001). Conclusion: The probability of survival of people living with HIV increases when they are diagnosed at a young age, in those with a CD4+ T Lymphocyte count ≥350 cells/μL, an undetectable viral load (<50 copies/mL) and are not in the AIDS stage.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Survival Analysis , Acquired Immunodeficiency Syndrome , Sex , T-Lymphocytes , Probability , HIV , Colombia , Lymphocyte Count , Viral Load , Survivorship
Medicina (B.Aires) ; 81(5): 683-687, oct. 2021. graf
Article in Spanish | LILACS | ID: biblio-1351038


Resumen La rápida propagación del coronavirus SARS-CoV-2, agente causal de la enfermedad pandémica emergente COVID-19 y sus nuevas variantes, requiere del compromiso de la comunidad inmunológica para comprender la magnitud y naturaleza de la respuesta inmunológica adaptativa desarrollada por pacientes recuperados de COVID-19 e individuos vacunados con diferentes estrategias y protocolos, a los fines de imple mentar nuevas políticas sanitarias. En la actualidad, la determinación de la inmunidad contra SARS-CoV-2 se basa principalmente en la detección de anticuerpos específicos y la determinación de su actividad neutralizante. Sin embargo, a pesar de la alta sensibilidad de estos ensayos, un número considerable de pacientes e indivi duos vacunados carecen de respuesta humoral detectable, o evidencian una disminución rápida de la misma en el tiempo. Con el objetivo de estudiar la respuesta inmune celular desencadenada frente a SARS-CoV-2, en nuestro laboratorio desarrollamos la "Plataforma COVID-T" estrategia integral optimizada dirigida a caracte rizar y monitorear la respuesta de linfocitos T específicos de SARS-CoV-2 a partir de muestras de sangre de individuos vacunados y/o recuperados de COVID-19. Esta plataforma permite evaluar la naturaleza, magnitud y persistencia de la inmunidad celular T generada tanto por la infección con SARS-CoV-2, como por distintos esquemas y protocolos de vacunación en diferentes poblaciones de individuos. Asimismo, permite evaluar la respuesta inmunológica T generada frente a nuevas variantes del virus e identificar individuos sanos resistentes a SARS-CoV-2 con inmunidad pre-existente hacia coronavirus estacionales.

Abstract The rapid spread of the SARS-CoV-2, the caus ative agent of the emergent pandemic disease COVID-19, requires the urgent commitment of the immunology community to understand the adaptive immune response developed by COVID-19 convalescent patients and individuals vaccinated with different strategies and schemes, with the ultimate goal of implementing and optimizing health care and prevention policies. Currently, assessment of SARS-CoV-2-specific immunity is mainly focused on the measurement of the antibody titers and analysis of their neutralizing capacity. However, a considerable proportion of individuals lack humoral responses or show a progressive decline of SARS-CoV-2-specific neutral izing antibodies. In order to study the cellular response of convalescent patients and vaccinated individuals, we have developed the 'COVID-T Platform', an optimized strategy to study SARS-CoV-2-specific T cell responses. This platform allows assessment of the nature, magnitude and persistence of antigen-specific T-cell immunity in COVID-19-convalescent patients and vaccinated individuals. Moreover, it gives the opportunity to study cellular responses against emerging coronavirus variants and to identify individuals with cross-reactive immunity against seasonal coronaviruses.

Humans , SARS-CoV-2 , COVID-19 , T-Lymphocytes , Antibodies, Neutralizing , Antibodies, Viral
Biomédica (Bogotá) ; 41(supl.2): 86-102, oct. 2021. graf
Article in English | LILACS | ID: biblio-1355762


Abstract | Introduction: Immunological markers have been described during COVID-19 and persist after recovery. These immune markers are associated with clinical features among SARS- CoV-2 infected individuals. Nevertheless, studies reporting a comprehensive analysis of the immune changes occurring during SARS-CoV-2 infection are still limited. Objective: To evaluate the production of proinflammatory cytokines, the antibody response, and the phenotype and function of NK cells and T cells in a Colombian family cluster with SARS-CoV-2 infection. Materials and methods: Proinflammatory cytokines were evaluated by RT-PCR and ELISA. The frequency, phenotype, and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with spike/RdRp peptides) were assessed by flow cytometry. Anti-SARS-CoV-2 antibodies were determined using indirect immunofluorescence and plaque reduction neutralization assay. Results: During COVID-19, we observed a high proinflammatory-cytokine production and a reduced CD56bright-NK cell and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by high IL-10 production. However, during recovery, we observed a bifunctional response characterized by the co-expression of CD107a and granzyme B or perforin. Conclusion: Although the proinflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells could be associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and to guide future immunotherapy strategies.

Resumen | Introducción. Se han descrito diferentes marcadores inmunológicos durante la COVID-19, los cuales persisten incluso después de la convalecencia y se asocian con los estadios clínicos de la infección. Sin embargo, aún son pocos los estudios orientados al análisis exhaustivo de las alteraciones del sistema inmunológico en el curso de la infección. Objetivo. Evaluar la producción de citocinas proinflamatorias, la reacción de anticuerpos, y el fenotipo y la función de las células NK y los linfocitos T en una familia colombiana con infección por SARS-CoV-2. Materiales y métodos. Se evaluaron las citocinas proinflamatorias mediante RT-PCR y ELISA; la frecuencia, el fenotipo y la función de las células NK (en cocultivos con células K562) y linfocitos T CD8+ (estimulados con péptidos spike/RdRp) mediante citometría de flujo, y los anticuerpos anti-SARS-CoV-2, mediante inmunofluorescencia indirecta y prueba de neutralización por reducción de placa. Resultados. Durante la COVID-19 hubo una producción elevada de citocinas proinflamatorias, con disminución de las células NK CD56 bright y reacción citotóxica. Comparados con los controles sanos, los individuos infectados presentaron con gran frecuencia linfocitos T CD8+ disfuncionales CD38+HLA-DR-. Además, en los linfocitos T CD8+ estimulados con péptidos virales, predominó una reacción monofuncional con gran producción de IL-10 durante la fase aguda y una reacción bifuncional caracterizada por la coexpresión de CD107a y granzima B o perforina durante la convalecencia. Conclusión. Aunque la reacción inflamatoria caracteriza la infección por SARS-CoV-2, hay otras alteraciones fenotípicas y funcionales en células NK y linfocitos T CD8+ que podrían asociarse con la progresión de la infección. Se requieren estudios adicionales para entender estas alteraciones y guiar futuras estrategias de inmunoterapia.

Coronavirus Infections , Killer Cells, Natural , T-Lymphocytes , Antibodies, Neutralizing , Inflammation
Medicina (B.Aires) ; 81(3): 337-345, jun. 2021. graf
Article in Spanish | LILACS | ID: biblio-1346468


Resumen Las leucemias agudas constituyen la neoplasia más frecuente en pacientes pediátricos. Actualmente, el 80% de los niños con leucemia linfoblástica aguda (LLA) logran curarse con quimioterapia con vencional pero el 20% de los mismos presentarán una reaparición de la enfermedad. La enfermedad residual medible (ERM) ha sido descripta como un importante factor pronóstico, que permite evaluar la respuesta de los pacientes al tratamiento. Una de las técnicas más sensibles par a estudiar ERM es la cuantificación de reordena mientos génicos de inmunoglobulinas (Ig) y receptores de linfocitos-T (TCR). Los objetivos del presente trabajo fueron describir los reordenamientos detectados de Ig/TCR, evaluar el efecto de la ERM en la supervivencia de niños con LLA y comparar la ERM por Ig/TCR con la cuantificada mediante citometría de flujo multiparamétrica (CFM). Del total de 455 pacientes estudiados, en el 96% fue posible caracterizar al menos un reordenamiento de Ig/TCR. El total de reordenamientos clonales detectados fue de 1550. La ERM pudo ser estudiada en forma exitosa en el 89% de los casos. El valor de ERM positiva combinada al día 33 y 78 de tratamiento, permitió identificar pacientes de alto riesgo, entre los previamente estratificados por la ERM mediante CFM al día 15. La comparación entre la determinación de ERM mediante reordenamientos Ig/TCR y CFM mostró una excelente correlación. El presente trabajo constituye un estudio de ERM mediante Ig/TCR realizado en un número muy significativo de pacientes diagnosticados en forma consecutiva, tratados en el marco de un protocolo homogéneo y con excelente seguimiento clínico.

Abstract Acute leukemias are the most common neoplasm in pediatric patients. Currently, 80% of children with diagnosis of acute lymphoblastic leukemia (ALL) are cured with conventional chemotherapy, but 20% of them will have a recurrence of the disease. Measurable Residual Disease (MRD) has been described as an important prognostic factor that allows evaluating the response of patients to treatment. One of the most sensitive techniques to study MRD is the quantification of immunoglobulins (Ig) and T-lymphocyte receptors (TCR) genes rearrangements. The aims of this study were to describe the detected Ig/TCR rearrangements, to evaluate the prognostic impact of MRD in our population of children with ALL and to compare the MRD values by Ig/TCR with those obtained by multiparametric flow cytometry (MFC). A total of 455 patients were studied. In 96% of the cases, it was possible to characterize at least one Ig/TCR rearrangement. The total number of Ig/TCR rear rangements detected was 1550. MRD was successfully applied in 89% of the cases. The combined positive MRD values at day 33 and 78 of treatment allow the identification of high-risk patients in cases previously stratified by MRD using flow cytometry at day 15. The comparison between MRD determination by Ig/TCR rearrangements and FC showed excellent correlation. The present work constitutes a study of MRD by Ig/TCR carried out in a very significant number of patients consecutively diagnosed, treated within a homogeneous protocol and with excellent clinical follow-up.

Humans , Child , Immunoglobulins , Gene Rearrangement, T-Lymphocyte , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes , Polymerase Chain Reaction , Neoplasm, Residual/genetics
Rev. cuba. estomatol ; 58(2): e3162, 2021. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1289399


Introducción: Las enfermedades de la cavidad bucal en los pacientes con VIH/sida pueden verse agravadas dependiendo de la respuesta inmunitaria del paciente y los niveles de linfocitos. Objetivo: Relacionar los niveles de linfocitos T CD4 y las principales lesiones bucales en pacientes con el VIH/sida del Hospital Nacional Hipólito Unanue (Lima, Perú), durante el 2018. Métodos: Se realizó un estudio analítico y de corte transversal, entre julio y octubre del 2018, en 65 pacientes hospitalizados, a los cuales se realizó un examen clínico de la cavidad bucal. Se evaluó la presencia de manifestaciones bucales asociadas al VIH/sida; también se clasificó el nivel de linfocitos T CD4 en tres categorías (> 500 cel/mm3, entre 200-500 cel/mm3 y < 200 cel/mm3). Resultados: Un 70,8 por ciento de los pacientes no se encontraba con tratamiento antirretroviral al momento del examen. El nivel promedio de linfocitos T CD4 fue 237,65 cel/mm3, con mayor prevalencia en mujeres. El 56,9 por ciento de los pacientes presentaron lesiones bucales, el sexo masculino fue el más afectado (91 por ciento). La lesión más frecuente fue la candidiasis bucal (44,6 por ciento) y la categoría que presentó mayor frecuencia de lesiones bucales fue la < 200 cel/mm3 (38,5 por ciento; p < 0,05). Conclusiones: El sexo masculino presentó la mayor cantidad de lesiones bucales asociadas a bajos niveles de linfocitos T CD4. La mayor parte de lesiones bucales se presentaron en un nivel de linfocitos T CD4 < 200 cel/mm3. La candidiasis bucal fue la lesión que más se evidenció al momento de realizar el examen clínico(AU)

Introduction: Oral diseases may be aggravated in HIV/AIDS patients depending on their immune response and lymphocyte levels. Objective: Describe the relationship between CD4 T lymphocyte levels and the main oral lesions in HIV/AIDS patients from Hipólito Unanue National Hospital in Lima, Peru, during the year 2018. Methods: An analytical cross-sectional study was conducted of 65 hospitalized patients from July to October 2018. The patients underwent oral clinical examination. Evaluation was performed of the presence of HIV/AIDS-related oral manifestations, and CD4 T lymphocyte levels were classified into three categories: > 500 cell/mm3, 200-500 cell/mm3 and < 200 cell/lmm3. Results: Of the total patients studied, 70.8 percent were not under antiretroviral treatment at the moment of the examination. Average CD4 T lymphocyte level was 237.65 cell/mm3, with higher results among women. 56.9 percent of the patients had oral lesions. Males were more commonly affected (91 percent). The most frequent lesion type was oral candidiasis (44.6 percent), whereas the category presenting the highest frequency of oral lesions was < 200 cell/mm3 (38.5 percent; p < 0.05). Conclusions: Male patients presented the largest number of oral lesions associated to low CD4 T lymphocyte levels. Most of the oral lesions were found at a CD4 T lymphocyte level < 200 cell/mm3. Oral candidiasis was the lesion most commonly found by the clinical examination(AU)

Humans , Male , Female , Candidiasis, Oral/etiology , T-Lymphocytes , Acquired Immunodeficiency Syndrome/epidemiology , Mouth/injuries , Cross-Sectional Studies
Fisioter. Bras ; 22(2): 154-167, Maio 25, 2021.
Article in Portuguese | LILACS | ID: biblio-1284095


Este estudo visa avaliar por eletromiografia de superfície o comportamento dos músculos inspiratórios no treinamento muscular em voluntários com vírus linfotrópico de célula T humana do tipo 1. Trata-se de um ensaio clínico. Sete voluntários, com idade 58,85 ± 7,2) anos, realizaram treinamento muscular inspiratório domiciliar por 4 semanas, 3 vezes por semana, 30 minutos diários por meio de incentivador de carga linear. Para avaliação utilizou-se os dados de pressão inspiratória máxima e os dados da eletromiografia de superfície nas fases pré (T0), segunda semana (T2) e após a quarta semana (T4) de treinamento. Observou-se aumento progressivo da força muscular inspiratória de T0 a T4 (p = 0,007), assim como, aumento do recrutamento das unidades motoras pela análise da amplitude do sinal eletromiográfico, sendo mais evidente para o músculo esternocleidomastóideo (p = 0,12) em comparação ao músculo diafragma (p = 0,6). Verificou-se que no decurso do treinamento muscular ocorreu melhora significativa da força muscular inspiratória com maior recrutamento das fibras musculares dos músculos analisados na amostra. (AU)

This study aimed to evaluate by surface electromyography the behavior of inspiratory muscles in the muscle training of volunteers with human T-cell lymphotropic virus type 1. This was a clinical trial. Seven volunteers, 58,85 ± 7.21 years old, underwent inspiratory muscle training at home for 4 weeks, 3 times a week, 30 minutes daily by means of a linear load stimulator. The maximum inspiratory pressure data and the surface electromyography data were used for evaluation in the pre (T0), second week (T2) and after the fourth week (T4) training phases. There was a progressive increase in inspiratory muscle strength from T0 to T4 (p = 0.007), as well as an increase in the recruitment of motor units by analyzing the amplitude of the electromyographic signal, being more evident for the sternocleidomastoid muscle (p = 0.12) in comparison to the diaphragm muscle (p = 0.6). During the muscle training inspiratory muscle strength improves with greater recruitment of muscle fibers from the muscles analyzed in the sample. (AU)

Humans , Middle Aged , Respiratory Muscles , Electromyography , T-Lymphocytes , Maximal Respiratory Pressures
J. pediatr. (Rio J.) ; 97(supl.1): 39-48, Mar.-Apr. 2021. tab, graf
Article in English | LILACS | ID: biblio-1250227


Abstract Objectives: Inborn Errors of Immunity (IEI), also known as primary immunodeficiencies, correspond to a heterogeneous group of congenital diseases that primarily affect immune response components. The main clinical manifestations comprise increased susceptibility to infections, autoimmunity, inflammation, allergies and malignancies. The aim of this article is to review the literature on combined immunodeficiencies (CIDs) focusing on the diagnosis and treatment and the particularities of the clinical management of these patients. Source of data: Critical integrative review, aimed to present articles related to primary immunodeficiencies combined with a searchin the PubMed and SciELO databases, with evaluation of publications from the last twenty years that were essential for the construction of knowledge on this group of diseases. Summary of data: We highlight the main characteristics of CIDs, dividing them according to their pathophysiological mechanisms, such as defects in the development of T cells, TCR signaling, co-stimulatory pathways, cytokine signaling, adhesion, migration and organization of the cytoskeleton, apoptosis pathways, DNA replication and repair and metabolic pathways. In CIDs, clinical manifestations vary widely, from sinopulmonary bacterial infections and diarrhea to opportunistic infections, caused by mycobacteria and fungi. Neonatal screening makes it possible to suspect these diseases before clinical manifestations appear. Conclusions: The CIDs or IEI constitute a complex group of genetic diseases with T-cell involvement. Neonatal screening for these diseases has improved the prognosis of these patients, especially in severe ones, known as SCIDs.

Humans , Infant, Newborn , Severe Combined Immunodeficiency , Immunologic Deficiency Syndromes/diagnosis , T-Lymphocytes , Neonatal Screening
Medicina (B.Aires) ; 81(1): 111-114, mar. 2021. graf
Article in Spanish | LILACS | ID: biblio-1287250


Resumen La leucemia/linfoma a células T del adulto (ATLL) es una enfermedad hematológica causada por el virus linfotrópico T humano tipo 1 (HTLV-1) que se desarrolla luego de 20 años de incubación, preferencialmente cuando la infección se adquiere por transmisión vertical. Este tiempo se reduce de 3 meses a 3 años cuando la transmisión del virus es por transfusión o trasplante de órganos. La ATLL aguda es de difícil diagnóstico por ser inusual y tener una rápida progresión a la muerte. En el Noroeste argentino, donde el virus es endémico, la ATLL es más frecuente, sin embargo, también se la detecta continuamente en el resto del país. El tratamiento de elección, en primera instancia, es el uso combinado de antivirales. Presentamos un caso de ATLL aguda desarrollada en un hombre de 59 años de Santiago del Estero a partir del cual se identificó transmisión intrafamiliar de la infección por HTLV-1.

Abstract Adult T-cell leukemia/lymphoma (ATLL) is an hematological disease caused by human T-cell lymphotropic virus type 1 (HTLV-1) that develops after 20 years of incubation preferentially when the infection is acquired by vertical transmission. In cases of transmission by transfusion or organ transplant, this time is reduced from 3 months to 3 years. Acute ATLL is difficult to diagnose because it is unusual and has a rapid progression to death. In the Argentine Northwest, where the virus is endemic, ATLL is more frequent, however it is also detected continuously in the rest of the country. The treatment of choice, in the first instance, is the combined use of antivirals. We present a case of acute ATLL developed in a 59-year-old man from Santiago del Estero from which intrafamilial transmission of HTLV-1 infection was identified.

Humans , Male , Adult , Middle Aged , Human T-lymphotropic virus 1/genetics , HTLV-I Infections/diagnosis , Leukemia-Lymphoma, Adult T-Cell/diagnosis , T-Lymphocytes
Electron. j. biotechnol ; 50: 59-67, Mar. 2021. ilus, graf, tab
Article in English | LILACS | ID: biblio-1292412


BACKGROUND: Cross talk of tumor­immune cells at the gene expression level has been an area of intense research. However, it is largely unknown at the alternative splicing level which has been found to play important roles in the tumor­immune microenvironment. RESULTS: Here, we re-exploited one transcriptomic dataset to gain insight into tumor­immune interactions from the point of AS level. Our results showed that the AS profiles of triple-negative breast cancer cells co-cultured with activated T cells were significantly changed but not Estrogen receptor positive cells. We further suggested that the alteration in AS profiles in triple-negative breast cancer cells was largely caused by activated T cells rather than paracrine factors from activated T cells. Biological pathway analyses showed that translation initiation and tRNA aminoacylation pathways were most disturbed with T cell treatment. We also established an approach largely based on the AS factor­AS events associations and identified LSM7, an alternative splicing factor, may be responsible for the major altered events. CONCLUSIONS: Our study reveals the notable differences of response to T cells among breast cancer types which may facilitate the development or improvement of tumor immunotherapy.

T-Lymphocytes , Triple Negative Breast Neoplasms , Peptide Chain Initiation, Translational , Gene Expression , Alternative Splicing , Cell Culture Techniques , Receptor Cross-Talk , Transfer RNA Aminoacylation , Transcriptome , Immunotherapy
Infectio ; 25(1): 49-54, ene.-mar. 2021. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1154402


Resumen La linfocitopenia T CD4 idiopática (LCI) es un síndrome clínico inusual que se caracteriza por un déficit de células T CD4+ circulantes en ausencia de infección por VIH u otra condición de inmunosupresión. Los pacientes con dicha enfermedad pueden presentarse asintomáticos o con infecciones oportunistas, las más frecuentes son por criptococo, micobacterias o virales como herpes zoster. Presentamos el caso de un hombre de 32 años, sin antecedentes, en quien se descartó infección por retrovirus, con recuento de linfocitos T CD4+ menor a 300 células/m3; se diagnosticó LCI posterior al diagnóstico de criptococomas cerebrales mediante hallazgos imagenológicos los cuales fueron congruentes con estudios microbiológicos.

Summary Idiopathic CD4 T lymphocytopenia (ICL) is an unusual clinical syndrome characterized by a deficit of circulating CD4 + T cells in the absence of HIV infection or another immunosuppression condition. Patients with this disease may present asymptomatic or with opportunistic infections, the most frequent are cryptococcus, mycobacteria or viral such as herpes zoster. We present a case of a 32-year-old man with no prior disease, in whom retrovirus infection was discarded, with CD4 + T lymphocyte count less than 300 cells/m3; ICL was diagnosed after the diagnosis of brain cryptococomas by imaging findings which were consistent with microbiological studies.

Humans , Male , Adult , Cryptococcosis , T-Lymphocytes , HIV Infections , HIV , Immunosuppression Therapy , Cryptococcus , Herpes Zoster , Lymphopenia
An. bras. dermatol ; 96(1): 76-81, Jan.-Feb. 2021. tab, graf
Article in English | LILACS | ID: biblio-1152788


Abstract Plasmacytoid dendritic cells are part of the dendritic cells family and are a relevant link between innate and adaptive immunity. They are the most potent producers of type 1 interferon, generating antiviral response, stimulating macrophages and dendritic cells and inducing activation and migration of natural killer cells. Plasmacytoid dendritic cells also exert a role as antigen-presenting cells, promote T-lymphocyte responses, immunoregulation, plasma cells differentiation and antibody secretion. Even though plasmacytoid dendritic cells are not usually present in normal skin, their presence is detected in healing processes, viral infections, and inflammatory, autoimmune, and neoplastic diseases. In recent years, the presence of plasmacytoid dendritic cells in several dermatological diseases has been described, enhancing their potential role in the pathogenesis of such conditions. Future studies on the role of plasmacytoid dendritic cells in dermatology may lead to new therapeutic targets.

Humans , Interferon Type I , Dermatology , Dendritic Cells , T-Lymphocytes , Immunity, Innate
An. bras. dermatol ; 96(1): 68-71, Jan.-Feb. 2021. graf
Article in English | LILACS | ID: biblio-1152783


Abstract Rosettes are small white structures visible with polarized light dermoscopy, whose exact morphological correlation is not yet defined. These small shiny structures are found in several conditions such as scarring, dermatofibroma, molluscum contagiosum, squamous cell carcinoma, basal cell carcinoma, melanoma, melanocytic nevus, discoid lupus erythematosus, and papulopustular rosacea. In this novel report, the authors describe the presence of rosettes in a T-cell pseudolymphoma lesion.

Humans , Skin Neoplasms , Pseudolymphoma/diagnosis , Melanoma , T-Lymphocytes , Dermoscopy
Article in Chinese | WPRIM | ID: wpr-880171


OBJECTIVE@#To explore the kinetics of infiltrated T cell in murine acute graft-versus-host disease (aGVHD) target organs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its relationship with tissue pathological damage and aGVHD progress.@*METHODS@#Male C57BL/6 (H-2K@*RESULTS@#Compared with BMT group, the number of infiltrated T cells in aGVHD target organs including liver, lung and gut increased since day 7 in BMT+T group (P<0.05). On day 14, 28, 40 and 47 after transplantation, more infiltrated CD3@*CONCLUSION@#Pathological damage of aGVHD target organs is induced by CD3

Animals , Bone Marrow Transplantation , Graft vs Host Disease , Kinetics , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , T-Lymphocytes , Transplantation, Homologous
Article in Chinese | WPRIM | ID: wpr-880131


OBJECTIVE@#To analyze the changes in the gene expression profile of T cells in CML patients after TCRζ up-regulation expression, and to explore the molecular mechanism of T cell reactivation after transgenic up-regulation of TCRζ.@*METHODS@#The peripheral blood mononuclear cells(PBMCs) from 3 newly untreated chronic-stage CML patients were collected, and the CD3@*RESULTS@#A total of 2248 differentially-expressed genes were obtained, including 553 up-regulated genes and 1695 down-regulated genes in experimental group as compared with those in control group (P<0.05) . The GO and KEGG enrichment analyses showed that differentially expressed genes involved in the biological processes related to T cell immune function, such as TCR signaling pathway, T cell proliferation and activation. Some of core genes involved in promoting the TCR signaling pathway, T cell proliferation, activation and apoptosis pathways were significantly up-regulated, while some core genes involved in inhibiting T cell activation were significantly down-regulated.@*CONCLUSION@#The molecular mechanism of the significantly improved T cell activation and proliferation ability in CML patients after TCRζ up-regulation may be related to the differential transcripts mediated signaling pathways of T cell activation, proliferation and apoptosis.

Humans , Leukocytes, Mononuclear , Lymphocyte Activation , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes , Up-Regulation