The Relationship between Occurrence of aGVHD in Patients with Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation and Immune Cell Components in Graft / 中国实验血液学杂志

OBJECTIVE@#To explore the relationship between occurrence of acute graft-versus-host disease (aGVHD) and various immune cell composition in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 104 patients with AML undergoing allo-HSCT in our hospital were retrospectively analyzed, and the hematopoietic reconstitution and occurrence of GVHD were analyzed. Flow cytometry was used to detect the proportion of various types of immune cells in the grafts, the number of graft composition in patients with different degrees of aGVHD was calculated and compared, and to analyze the correlation between the severity of aGVHD in AML patients after allo-HSCT and the immune cell components in the graft.@*RESULTS@#There was no significant difference in the time of hematopoietic reconstitution between the high number group of total number of nucleated cells (TNC) and the low number group, while the time of neutrophil and platelet reconstruction in the high number of CD34 group was significantly faster than that in the low number of CD34 group (P＜0.05), and the total hospital stay also tends to be shorten. Compared with patients in 0-Ι aGVHD group, both HLA-matched and HLA-haploidentical transplantation, the infusion amounts of CD3+ cells, CD3+CD4+ cells, CD3+CD8+ cells, NK cells and CD14+ monocytes were higher in patients of Ⅱ-Ⅳ aGVHD group， but the difference was not statistically significant (P>0.05); In addition, in patients with HLA-haploidentical transplantation, the number of CD4+CD25+ cells in Ⅱ-Ⅳ aGVHD group was significantly lower than that in 0-Ι aGVHD group (P<0.05), and the same trend was also observed in HLA-matched transplanted patients, but the difference was not significant (P=0.078).@*CONCLUSION@#High number of CD34+ cells in the graft is beneficial to hematopoietic reconstitution in AML patients. To a certain degree, high number of CD3+ cells, CD3+CD4+ cells, CD3+CD8+ cells, NK cells and CD14+ cells tend to increase the occurrence of aGVHD, but high number of CD4+CD25+ regulatory T cells is beneficial to reduce the incidence of aGVHD in AML patients.

Development of a flow cytometry method for detection of bovine multi-cytokines / 生物工程学报

This study aims to develop a method to detect bovine multi-cytokines based on flow cytometry. Previously we have prepared and screened monoclonal antibodies against bovine cytokines IFN-γ, IL-2, TNF-α, IP-10 and MCP-1. These bovine cytokine monoclonal antibodies were fluorescently labeled, and the combination of antibody and cell surface molecules were used to develop the method for detecting bovine multi-cytokines. Subsequently, the developed method was used to determine the cytokine expression profile of Mycobacterium bovis BCG infected bovine peripheral blood mononuclear cells in vitro, and evaluate the cytokine expression level of peripheral blood CD4+ T cells of tuberculosis-positive cattle. The bovine multi-cytokine flow cytometry detection method can effectively determine the cytokine expression of BCG-infected bovine peripheral blood T lymphocytes. Among them, the expression levels of IFN-γ, IL-2, and TNF-α continue to increase after 40 hours of infection, while the expression levels of IP-10 and MCP-1 decreased. The combined detection of IFN-γ, IL-2, and TNF-α on CD4+ T lymphocytes in peripheral blood of cattle can effectively distinguish tuberculosis-positive and tuberculosis-negative samples. This method may facilitate evaluating the level of cellular immune response after bovine pathogen infection and vaccine injection.

Effect of expressing of anti-PD-1 antibody in mouse mammary gland on spleen T cells in transgenic mice / 生物工程学报

This study aims to investigate the effect of anti-PD-1 antibody expressed in mouse mammary gland on the surface antigen protein of spleen T cells, cytokine expression, spleen CD4+ T cell proliferation and proliferation related pathways of transgenic mice at the cellular level. Transgenic mice expressing anti-human PD-1 antibody at 8 weeks of age without pregnancy and 18 weeks of age with lactation were divided into two groups, with transgenic negative mice in each group as the control. Spleen lymphocytes were extracted and the changes of spleen lymphocytes were detected. Compared with transgenic negative mice, the proportion of effector T cells of spleen T cells in the immune system of transgenic mice with anti-PD-1 antibody expressed in breast increased, the proportion of Treg cells decreased, and the IFN-γ, IL-17 and IL-2 expressed in CD4+ T cells increased in varying degrees. Moreover, IL-4, IL-10 and TGF-β in CD4+ T cells did not change, nor did some cell surface protein molecules related to T cell stimulate. There was no significant difference in T cell proliferation between transgenic positive and transgenic negative mice. In transgenic positive mice, the expression of phosphorylated proteins in PI3K/Akt/mTOR and RAS/MEK/ERK pathways were partially up-regulated, but the whole pathway was not completely up-regulated. Therefore, it is feasible to use transgenic mice as host to express monoclonal antibodies related to immune system such as anti-PD-1 antibody.

Levels of base excision repair proteins in CD4+ T cells in patients with systemic lupus erythematosus / 中南大学学报(医学版)

OBJECTIVES@#Systemic lupus erythematosus (SLE) is a multi-systemic disease with the unknown pathogenic mechanism. DNA demethylation is involved in SLE pathogenesis. Growth arrest and DNA damage inducible 45 alpha (Gadd45a) takes part in the process of DNA demethylation. Gadd45a is a DNA repair-related protein. This study aims to investigate the expressions of some proteins [including activation-induced cytidine deaminase (AID), thymine DNA glycosylase (TDG), and methyl-CpG-binding domain protein 4 (MBD4)] involving in base excision repair (BER) process in CD4+ T cells in patients with SLE, and to analyze the correlations between the above BER proteins and lupus disease.@*METHODS@#From January 2019 to September 2020, 12 SLE patients and 12 healthy controls were recruited from Second Xiangya Hospital of Central South University. Peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Hypaque density gradient centrifugation and then CD4+ T cells were isolated via positive selection using Miltenyi beads. We measured the messenger RNA (mRNA) and protein expressions of AID, TDG, and MBD4 by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, respectively.@*RESULTS@#In contrast to controls, in SLE CD4+ T cells, the mRNA and protein expressions of AID were elevated (P=0.003, P=0.022, respectively); TDG protein expression was increased (P=0.017); and MBD4 protein level was reduced (P<0.001). No visible distinctions was found in the mRNA expressions of either TDG or MBD4 between the 2 groups (both P>0.05). The mRNA and protein expressions of AID and the protein levels of TDG were positively correlated with SLE disease activity index (SLEDAI). And the mRNA and protein expressions of MBD4 were negatively correlated with SLEDAI.@*CONCLUSIONS@#In SLE CD4+ T cells, the increased expressions of AID and TDG and the decreased MBD4 expression may participate in SLE pathogenic mechanism.

Cornuside ameliorated experimental autoimmune encephalomyelitis by limiting the recruitment of CD4+ T lymphocytes in the spinal cord

We conducted this study to determine whether cornuside could improve the neurological deficit symptoms of experimental autoimmune encephalomyelitis (EAE) rats, as well as determine the potential involvement of CD4+ T lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α). Altogether, 32 Lewis rats were randomly divided into control, EAE, EAE/prednisolone, and EAE/cornuside, wherein their neurological function was assessed every day. CD4+ T lymphocyte recruitment into the spinal cord (SC) was evaluated using immunohistochemistry. The VCAM-1, ICAM-1 and TNF-α mRNA expressions in the SC were determined by real-time quantitative PCR, and the VCAM-1 and ICAM-1 proteins were determined by western blotting. Compared to the control group, the EAE group rats with neurological deficits had enhanced CD4+ T lymphocyte infiltration and higher expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Meanwhile, compared with the EAE group, the EAE/cornuside and EAE/prednisolone groups had lower neurological scores, less CD4+ T lymphocyte infiltrations, and lower expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Thus, cornuside ameliorated EAE, which could be owed to the inhibition of CD4+ T lymphocyte recruitment and VCAM-1, ICAM-1, and TNF-α expressions in the SC

Cellular infiltrate in cutaneous leishmaniasis lesions and therapeutic outcome

Abstract Background: The treatment of cutaneous leishmaniasis is a challenge. A better understanding of the in situ mechanisms involved in the evolution and cure of the disease is essential for the development of new therapies. Objective: Correlate histopathological and immunological characteristics of cutaneous leishmaniasis lesions with clinical outcome after different treatment regimens. Methods: The authors analyzed cellular infiltration and immunohistochemistry staining for CD4, CD8 and IL-17 in biopsy samples from 33 patients with cutaneous leishmaniasis before treatment. All patients were recruited in a randomized clinical trial at Corte de Pedra (Bahia-Brazil) and assigned to receive Glucantime®, Glucantime® + Oral Tamoxifen or Glucantime® + Topical Tamoxifen. Patients were followed for 2 to 6 months to define disease outcome. Results: A similar expression of CD4, CD8 and IL-17 was observed in lesion samples regardless of clinical outcome. In general, a higher amount of CD8 cells were observed compared with CD4 cells. An important observation was that all patients whose cellular infiltrate did not contain plasma cells were cured after treatment. Study limitations: Isolated quantification of TCD8 and IL-17 using immunohistochemistry is insufficient to analyze the role of these molecules in the immunopathogenesis of cutaneous leishmaniasis. In addition, the expansion of the immunohistochemistry panel would allow a more complete analysis of the immune response in situ. Conclusions: The absence of plasma cells in cutaneous leishmaniasis lesions was related to a favorable therapeutic outcome.

AIDS in the meeting of the Tapajós and Amazon rivers: deaths in the period 2010-2018 in Santarém, Pará, Brazil / AIDS no encontro dos rios Tapajós e Amazonas: óbitos no período de 2010-2018 em Santarém, Pará, Brasil

INTRODUCTION: The city of Santarém, the regional healthcare center in the western Pará State, lacks studies on the epidemic of the human immunodeficiency virus (HIV), in particular, on the causes of death. OBJECTIVE: To characterize the sociodemographic and clinical profile related to the evolution of HIV infection to death. METHODS: The sample consisted of 94 medical records of patients from a reference center in the city of Santarém-PA, who died between 2010-2018. Data were collected on the sociodemographic profile, immunological and clinical characteristics of the patients. Data were analyzed using descriptive and inferential statistics, adopting p<0.05. RESULTS: Most deaths were male (67%), aged between 15-29 years (39%) and diagnosed between 30-44 years (41%), single (54%), mixed race (91.5%), from Santarém (77%) and with sexual intercourse being the main type of exposure (95.7%). Most patients were not being treated at the moment of death (56.4%), the main cause of death was respiratory failure (5%), in which, these individuals had, at the moment of death, TCD4+ lymphocytes <200 cell/mm3 (26%) and detectable viral load (29%). CONCLUSION: The lifetime from diagnosis to death was 48.45±50,30 months, and immunosuppression in the diagnosis was positively associated with the shortest survival time. However, sex was not associated with the immunological profile, age at the time of diagnosis, and death. There was only a tendency for women towards immunosuppression and detectable viral load.

INTRODUÇÃO: A cidade de Santarém, o polo assistencial da região oeste do Pará, carece de estudos sobre a epidemia do vírus da imunodeficiência humana (HIV), especialmente, sobre as causas de óbitos. OBJETIVO: Caracterizar o perfil sociodemográfico e clínico relacionado à evolução da infecção pelo HIV até a morte. MÉTODO: A amostra foi de 94 prontuários de pacientes de um centro de referência do município de Santarém-PA, que evoluíram a óbito entre os anos de 2010-2018. Foram levantados os dados sobre o perfil sociodemográfico, características imunológicas e clínicas dos pacientes. Os dados foram analisados por estatística descritiva e inferencial, adotando-se p<0,05. RESULTADOS: A maioria dos óbitos foi de indivíduos do sexo masculino (67%), com faixa etária do diagnóstico entre 15-29 anos (39%) e de falecimento entre 30-44 anos (41%), solteiros (54%), pardos (91,5%), procedentes de Santarém (77%) e com a relação sexual sendo o principal tipo de exposição (95,7%). A maioria dos pacientes não estava em tratamento no momento do óbito (56,4%), a principal causa de morte foi por insuficiência respiratória (5%), no qual, esses indivíduos apresentavam, no momento da morte, linfócitos TCD4+ <200 cél/mm3 (26%) e carga viral detectável (29%). CONCLUSÃO: O tempo de vida do diagnóstico ao óbito foi de 48,45±50,30 meses e a presença de imunossupressão no diagnóstico associou-se positivamente com o menor tempo de sobrevida. Contudo, o sexo não apresentou associação com o perfil imunológico, a idade no momento do diagnóstico e do óbito, apenas notou-se uma tendência das mulheres para a imunossupressão e carga viral detectável.

Association between circulating exhausted CD4+ T cells with poor meningococcal C conjugate vaccine antibody response in HIV-infected children and adolescents

OBJECTIVES: To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC). METHODS: HI patients (n=12), aged 8-17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3-10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1-18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits. RESULTS: The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells. CONCLUSION: The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients.

Immunomodulatory effect of adriamycin in mouse 4T1 model of breast cancer / 生物工程学报

To explore the immunomodulatory effect of adriamycin on 4T1 breast cancer. We used a tandem mass tag-based quantitative proteomic method to detect differential proteins in breast cancer tissues, and multiple bioinformatics databases to analyze the differentially expressed proteins in the proteome. Also, we used enzyme-linked immunosorbent assay to detect the effects of adriamycin on helper T cells 1 and 2 in breast cancer tissues, and flow cytometry to detect CD4+ T cells, CD8+ T cells and regulatory T cells. We discovered the immunomodulatory targets of adriamycin in differential proteins. In total 170 differential proteins were significantly up-regulated, whereas 58 were markedly down-regulated. In addition, 73 proteins were involved in immune regulation. Kyoto encyclopedia of genes and genomes enriched important protein pathways related to cytokines and factor receptors, interleukin 17 pathway and cancer transcriptional regulatory pathways. These pathways and important differential proteins related to immunomodulatory functions were ultimately regulated by adriamycin on CD4+ T cells, CD8+ T cells and regulatory T cells, thereby affecting the prognosis of breast cancer. Moreover, adriamycin significantly increased interleukin 2, CD4+ T and CD8+ T (P<0.01) and markedly reduced regulatory T cells (P<0.05). The function of adriamycin against triple-negative breast cancer was closely related to the immunoregulation process of the differential proteins Ighm, Igkc, S100A8, S100A9 and Tmsb4x. Adriamycin could regulate the content of helper T cells 1 cytokines, CD4+ T and CD8+ T lymphocytes in breast cancer and reduce the number of regulatory T cells to produce immunomodulatory effects.

Alterations in thymocyte populations under conditions of endotoxin tolerance / 中华医学杂志(英文版)

BACKGROUND@#Endotoxin tolerance (ET) is a protective phenomenon in which pre-treatment with a tolerance dose of lipopolysaccharide (LPS) leads to dramatically elevated survival. Accumulating evidence has shown that peripheral T cells contribute to the induction of ET. However, what happens to T cell development in the thymus under ET conditions remains unclear. The purpose of this study was to analyze the alterations in thymocyte populations (double-positive [DP] and single-positive [SP] cells) under ET conditions.@*METHODS@#Mice were intraperitoneally injected with LPS at a concentration of 5 mg/kg to establish an LPS tolerance model and were divided into two groups: a group examined 72 h after LPS injection (72-h group) and a group examined 8 days after LPS injection (8-day group). Injection of phosphate-buffered saline was used as a control (control group). Changes in thymus weight, cell counts, and morphology were detected in the three groups. Moreover, surface molecules such as CD4, CD8, CD44, CD69, and CD62L were analyzed using flow cytometry. Furthermore, proliferation, apoptosis, cytokine production, and extracellular signal-regulated kinase (ERK) pathway signaling were analyzed in thymocyte populations. The polymorphism and length of the T-cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) were analyzed using capillary electrophoresis DNA laser scanning analysis (ABI 3730).@*RESULTS@#Thymus weight and cell counts were decreased in the early stage but recovered by the late stage in a murine model of LPS-induced ET. Moreover, the proportions of DP cells (control: 72.130 ± 4.074, 72-h: 10.600 ± 3.517, 8-day: 84.770 ± 2.228), CD4+ SP cells (control: 15.770 ± 4.419, 72-h: 44.670 ± 3.089, 8-day: 6.367 ± 0.513), and CD8+ SP cells (control: 7.000 ± 1.916, 72-h: 34.030 ± 3.850, 8-day: 5.133 ± 0.647) were obviously different at different stages of ET. The polymorphism and length of TCR β chain CDR3 also changed obviously, indicating the occurrence of TCR rearrangement and thymocyte diversification. Further analysis showed that the expression of surface molecules, including CD44, CD69, and CD62L, on thymocyte populations (DP and SP cells) were changed to different degrees. Finally, the proliferation, apoptosis, cytokine production, and ERK pathway signaling of thymocyte populations were changed significantly.@*CONCLUSION@#These data reveal that alterations in thymocyte populations might contribute to the establishment of ET.

Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs: a promising therapeutic strategy for HIV cure / 中华医学杂志(英文版)

Many seminal advances have been made in human immunodeficiency virus (HIV)/AIDS research over the past four decades. Treatment strategies, such as gene therapy and immunotherapy, are yielding promising results to effectively control HIV infection. Despite this, a cure for HIV/AIDS is not envisioned in the near future. A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS, referred to as "selective elimination of host cells capable of producing HIV" (SECH). Similar to the "shock and kill strategy," the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs. Herein, we comprehensively review the specific mechanisms targeted by the SECH strategy. Briefly, the suggested cocktail of drugs should contain (i) latency reversal agents to promote the latency reversal process in replication-competent reservoir cells, (ii) pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways, and finally (iii) drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells, and by HIV integrase inhibitor drugs. Finally, we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.

Comparative evaluation of memory T cells in COVID-19 patients and the predictive role of CD4+CD8+ double positive T lymphocytes as a new marker

SUMMARY BACKGROUND: The COVID-19 pandemic has affected the entire world, posing a serious threat to human health. T cells play a critical role in the cellular immune response against viral infections. We aimed to reveal the relationship between T cell subsets and disease severity. METHODS: 40 COVID-19 patients were randomly recruited in this cross-sectional study. All cases were confirmed by quantitative RT-PCR. Patients were divided into two equivalent groups, one severe and one nonsevere. Clinical, laboratory and flow cytometric data were obtained from both clinical groups and compared. RESULTS: Lymphocyte subsets, CD4+ and CD8+ T cells, memory CD4+ T cells, memory CD8+ T cells, naive CD4+ T cells, effector memory CD4+ T cells, central memory CD4+ T cells, and CD3+CD4+ CD25+ T cells were significantly lower in severe patients. The naive T cell/CD4 + EM T cell ratio, which is an indicator of the differentiation from naive T cells to memory cells, was relatively reduced in severe disease. Peripheral CD4+CD8+ double-positive T cells were notably lower in severe presentations of the disease (median DP T cells 11.12 µL vs 1.95 µL; p< 0.001). CONCLUSIONS: As disease severity increases in COVID-19 infection, the number of T cell subsets decreases significantly. Suppression of differentiation from naive T cells to effector memory T cells is the result of severe impairment in adaptive immune functions. Peripheral CD4+CD8+ double-positive T cells were significantly reduced in severe disease presentations and may be a useful marker to predict disease severity.

RESUMO OBJETIVO: A pandemia de COVID-19 tem afetado o mundo todo, constituindo uma ameaça grave para a saúde humana. As células T desempenham um papel crítico na imunidade celular contra infecções virais. Procuramos desvendar a relação entre sub grupos de células T e a severidade da doença. MÉTODOS: Um total de 40 pacientes com COVID-19 foram aleatoriamente recrutados para o presente estudo transversal. Todos os casos foram confirmados por RT-PCR quantitativo. Os pacientes foram divididos em dois grupos equivalentes, um grave e um não-grave. Os dados da avaliação clínica, laboratorial e da citometria de fluxo foram obtidos para ambos os grupos e comparados. RESULTADOS: Os subconjuntos de linfócitos, células T CD4+ e CD8+, células T de memória CD4+, células T de memória CD8+, células T CD4+ virgens, células T efetoras CD4+, células T de memória central CD4+ e células T CD3+ CD4+ CD25+ estavam significativamente mais baixas nos pacientes graves. A razão células T virgens/células T efetoras TCD4+, que é um indicador da diferenciação entre células T virgens e células de memória, estava relativamente reduzida em casos graves da doença. As células T duplo-positivas CD4+CD8+ periféricas estavam notavelmente mais baixas em casos graves da doença (mediana das células T DP: 11,12 µL vs. 1,95 µL; p< 0,001). CONCLUSÃO: Conforme aumenta a gravidade da doença nos casos de COVID-19, o número de subconjuntos de células T diminui significativamente. A supressão da diferenciação de células T virgens para células T efetoras é o resultado do comprometimento grave das funções imunológicas adaptativas. As células T duplo-positivas CD4+CD8+ periféricas estavam notavelmente mais baixas em casos graves da doença e podem ser um marcador útil para predizer a severidade da doença.

Respuesta inmune Th1/Th2 en pacientes co-infectados con Helicobacter pylori y helmintos / Immune response Th1/Th2 to Helicobacter pylori and Helminths in co-infected patients

Resumen: Introducción: La inflamación asociada con la infección por Helicobacter pylori (H. pylori) se relaciona con la pro gresión de las lesiones precancerosas gástricas. Las infecciones por helmintos podrían modular la respuesta proinflamatoria a la infección por H. pylori desde un perfil tipo LTCD4+ Th1 hacia una respuesta menos perjudicial tipo LTCD4+ Th2. Objetivo: Caracterizar la polarización de la respuesta inmune tipo LTCD4+ Th1/Th2 de pacientes coinfectados por H. pylori y helmintiasis procedentes de áreas de bajo riego para el desarrollo de cáncer gástrico. Pacientes y Método: Se analizaron 63 pacientes, 40 adultos y 23 niños infectados con H. pylori. La determinación de los perfiles séricos de las interleucinas asociadas con la polarización de la respuesta inmune tipo LTCD4+ Th1 (IL-1Β, INF-γ y TNF-α) y tipo LTCD4+ Th2 (IL-4, IL-10 e IL-13) se realizó con Análisis Multiplex (xMAP). La relación entre el estado de coinfección por helmintos en pacientes infectados con H. pylori y la polarización de la respuesta inmune mediada por LTCD4+ Th1 y LTCD4+ Th2, se estudió con un modelo de regresión logístico de efectos mixtos. Resultados: La frecuencia de helmintos fue similar en adultos (15%) y niños (17%). La polarización de la respuesta inmune fue más prevalente hacia el tipo LTCD4+ Th1. Los valores séricos de las interleucinas asociadas con la polarización de la respuesta inmune tipo LTCD4+ Th1 (IL-1 Β, INF-γ y TNF-α) y tipo LTCD4+ Th2 (IL-4, IL-10 e IL-13) fueron independientes del estado de infestación por helmintos. Conclusión: La prevalencia de infección por parasitismo intestinal fue alta y la polarización de la respuesta inmune fue predominantemente hacia un perfil tipo LTCD4 + Th1.

Abstract: Introduction: Inflammation associated with Helicobacter pylori (H. pylori) infection is linked to the development of a gastric precancerous lesion. Helminth infections could influence the pro-inflam matory response to such infection from LTCD4+ Th1 to a less harmful LTCD4+ Th2 response. Ob jective: To characterize the polarization of the LTCD4+ Th2 immune response in co-infected pa tients with H. pylori and helminths from low-risk areas for developing gastric cancer. Patients and Method: We analyzed 63 patients infected by H. pylori (40 adults and 23 children). Through the Multiplex Analysis technology (xMAP), we determined the serum profiles of the interleukins asso ciated with the polarization of the immune response of LTCD4+ Th1 (IL-1Β, INF-γ, TNF-α) as well as the LTCD4+ Th2 (IL-4, IL-10, and IL-13). The ratio between helminths co-infection status in H. pylori-infected patients and the polarization of the immune response mediated by LTCD4+ Th1 and LTCD4+ Th2 was assessed using a Mixed Effects Logistic Regression Model. Results: The frequency of helminths was similar between adults (15%) and children (17%). The polarization of the immu ne response was more prevalent in LTCD4+ Th1. Serum values of interleukins associated with the immune response polarization of LTCD4+ Th1 (IL-1Β, INF-γ, and TNF-α) and LTCD4+ Th2 (IL-4, IL-10, and IL-13) were independent of helminths infection status. Conclusion: The prevalence of in testinal parasitic infection was high and the immune response polarization was mainly LTCD4 + Th1.

Epidemiological profile of HIV older adults who are patients in a reference center in Aracaju-SE / Perfil epidemiológico dos pacientes idosos com HIV em um centro de referência de Aracaju-SE / Perfil epidemiológico de pacientes ancianos con VIH en un centro de referencia en Aracaju-SE

Background and objectives: Acquired Immunodeficiency Syndrome (AIDS) is a disease caused by HIV. 3% of the people living with HIV/AIDS in Brazil are 60 years old or over. Although older adults correspond to a small percentage, there has been a significant increase in the incidence in this group in recent years. Thus, HIV infection in older adults is a reality, however, literature hardly addresses this topic. The objective is to study the epidemiological clinical profile of older adults living with HIV monitored at a referral center. Methods:This is an observational, descriptive, cross-sectional study with data collection obtained from the medical records of the STI/AIDS outpatient clinic at a reference center. The data were sociodemographic, clinical and laboratory, collected from September 2018 to February 2019. Results:In the reference center, 309 older adults were registered, representing 6.7% of all patients registered in the service. Of these, 75.6% are men, 38% are married, 70% heterosexual and approximately 50% with low education. Comorbidities are associated, with dyslipidemia (54%) being the main one. At the time of diagnosis, 65.8% had detectable viral load and 62% had CD4 + cells <500 cls/mm³ and after therapeutic follow-up, only 20% had detectable viral load. Several therapeutic regimens are used, the main one being Tenofovir, Lamivudine and Efavirenz (35.3%). Conclusion: The epidemiological profile of the population served in the region follows national and global characteristics, with a predominance of men, heterosexuals, married and with low education.(AU)

Justificativa e Objetivos: A Síndrome da Imunodeficiência Adquirida (SIDA) é uma doença causada pelo HIV. Das pessoas vivendo com HIV(PVHIV)no Brasil, 3% apresentam 60 anos ou mais. Apesar dos idosos corresponderem a um pequeno percentual, há aumento significativo da incidência nesse grupo nos últimos anos. Dessa forma, a infecção pelo HIV em idosos é uma realidade, contudo, a literatura pouco aborda esse tema. O objetivo do trabalho é estudar o perfil clínico epidemiológico dos idosos vivendo com HIV acompanhados em um centro de referência. Métodos: Trata-se de um estudo observacional, descritivo, de corte transversal, com coleta de dados obtida através dos prontuários do ambulatório de IST/SIDA de um centro de referência. Os dados sociodemográficos, clínicos e laboratoriais, foram coletados no período setembro de 2018 a fevereiro de 2019. Resultados: No centro de referência, estão cadastrados 309 idosos, representando 6,7% de todos os pacientes matriculados no serviço. Destes, 75,6% são homens, 38% casados, 70% de orientação heterossexual e aproximadamente 50% com baixa escolaridade. Comorbidades estão associadas, sendo a dislipidemia (54%) a principal. No momento do diagnóstico, 65,8% apresentavam carga viral (CV) detectável,62% tinham células CD4+ < 500céls/mm³ e após seguimento terapêutico apenas 20% apresentavam CV detectável. Vários esquemas terapêuticos foram utilizados, sendo o principal Tenofovir, Lamivudina e Efavirenz (35,3%). Conclusão: O perfil epidemiológico da população atendida na região segue as características nacionais e mundiais, com predomínio de homens, heterossexuais, casados e de baixa escolaridade.(AU)

Justificación y Objetivos: El Síndrome de Inmunodeficiencia Adquirido(SIDA) es una enfermedad causada por el VIH. De las personas que viven con el VIH (PVVIH) en Brasil, el 3% tiene 60 años o más. Aunque los adultos mayor es corresponden a un pequeño porcentaje, en los últimos años se ha producido un aumento significativo de la incidencia en este grupo. La infección por VIH en los adultos mayores es una realidad; sin embargo, la literatura aborda poco este tema. El objetivo de este trabajo es estudiar el perfil clínico epidemiológico de adultos mayores que conviven con el VIH y se atienden en un centro de referencia. Métodos: Se trata de un estudio observacional, descriptivo, de corte transversal, con datos obtenidos de los registros de ETS/SIDA de un centro de referencia. Se recogieron datos sociodemográficos, clínicos y de laboratorio desde septiembre de 2018 hasta febrero de 2019. Resultados: En el centro de referencia están registrados309 adultos mayores, que representan el 6,7% de todos los pacientes inscriptos en el servicio. De ellos, el 75,6% es del sexo masculino, el 38%, casado, el 70% con orientación heterosexual y aproximadamente el 50% con baja escolaridad. De las comorbilidades asociadas, la dislipidemia esla principal (54%). En el momento del diagnóstico, el 65,8% tenía una carga viral detectable (CV), el 62%tenía células CD4+<500 células/mm³ y después del seguimiento terapéutico sólo el 20% tenía CV detectable. Se utilizaron varios esquemas terapéuticos, siendo los principales el Tenofovir, la Lamivudina y el Efavirenz (35,3%). Conclusión: El perfil epidemiológico de la población atendida en la región sigue las características nacionales e internacionales, con predominio de hombres heterosexuales, casados y de baja escolaridad.(AU)

Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294

ABSTRACT Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.

Caracterización de las manifestaciones otorrinolaringológicas en pacientes con infección por VIH/Sida en la ciudad de Cartagena / Characterization of the otorrinolaringological manifestations in patients with HIV/AIDS infection in the city of Cartagena

Introducción: en Colombia, la incidencia por virus de inmunodeficiencia humana (VIH) ha ido en aumento; la ciudad de Cartagena tiene una de las más altas del país. Las manifestaciones otorrinolaringológicas en personas con VIH se estiman entre un 20%-80%, lo que genera un gran impacto en la calidad de vida. Objetivo: determinar las características epidemiológicas y las manifestaciones otorrinolaringológicas en un grupo de personas con VIH/Sida de la ciudad de Cartagena. Metodología: diseño observacional descriptivo de corte transversal y prospectivo. Se recolectó información de pacientes con VIH de la ciudad de Cartagena, que asistieron a dos centros médicos. Se les aplicó un cuestionario para obtener datos epidemiológicos, signos y síntomas otorrinolaringológicos, así como un examen físico otorrinolaringológico completo. Resultados: se incluyeron 150 pacientes en el estudio, con una media de edad de 31 años, 59,3% del género masculino y 40,7% del femenino. El antecedente patológico no otorrinolaringológico más frecuente fue la coinfección por sífilis en un 10%; el otorrinolaringológico fue la sinusitis y la candidiasis oral, cada uno con un 3,3%. El 73% de los pacientes manifestó alteración otorrinolaringológica en el momento de la evaluación. Las más frecuentes fueron las otológicas, con el 39,9% de los pacientes. Además, se observó una relación estadísticamente significativa entre los conteos de CD4 y hallazgos como disfonía en laringe (p = 0,045). Conclusiones: las manifestaciones otológicas fueron las más frecuentes en nuestro medio y se encontró una relación entre el conteo de CD4 y las manifestaciones laríngeas de la enfermedad.

Introduction: In Colombia, the incidence of the disease has been increasing and Cartagena has the highest numbers of the country. Otorhinolaryngological manifestations in people with HIV/AIDS are estimated between 20%-80% generating a great impact on quality of life. Objective: To determine the epidemiological characteristics and otorhinolaryngological manifestations in a group of people with HIV / AIDS in the city of Cartagena. Methodology: Observational, descriptive, cross-sectional and prospective design. Information was collected from patients with HIV from the city of Cartagena who attended 2 medical centers, a questionnaire was applied to obtain epidemiological data, otorhinolaryngological signs and symptoms, as well as a complete otorhinolaryngological physical examination. Results: 150 patients were included in the study, with a mean age of 31 years, 59.3% male and 40.7% female. The most frequent non-otorhinolaryngological pathological antecedent was syphilis coinfection in 10% and otorhinolaryngological, sinusitis and oral candidiasis each with 3.3%. 73% of the patients at the time of the evaluation manifested otorhinolaryngological alteration, the otological ones being the most frequent with 39.9% of the patients. Furthermore, a significant relationship was observed between CD4 counts and findings such as laryngeal dysphonia (p = 0.045). Conclusions: The otological manifestations were the most frequent in our environment and a relationship was found between the CD4 count and the laryngeal manifestations of the disease.

Consumo de álcool de pessoas vivendo com HIV e suas implicações para os desfechos clínicos / Alcohol consumption in people living with HIV and its implications for clinical outcomes

Objetivou-se analisar a prevalência do consumo de álcool em pessoas vivendo com HIV e sua associação com os desfechos clínicos. Trata-se de um estudo transversal, analítico, realizado com pessoas que vivem com HIV em tratamento ambulatorial no município de Ribeirão Preto, SP. Realizou-se entrevista com instrumento sociodemográfico e clínico e com o Cuestionario para La Evaluación de La Adhesión al Tratamiento Antirretroviral. Para análise dos dados utilizou-se os Testes Qui-quadrado, Exato de Fisher e regressão logística, adotando p<0,05. Dos 340 participantes, a prevalência do consumo de álcool foi 40,6%, dos quais 35% apresentavam consumo leve e moderado e 5,6% alto. Identificou-se que pessoas com carga viral detectável tem 1,76 vezes mais chance (p=0,04; IC95% 1,00­3,05) de consumir álcool. O estudo evidenciou uma alta prevalência de consumo de álcool entre pessoas que vivem com HIV e o desfecho clínico que apresentou associação com o alto consumo de álcool foi a carga viral.

This study aimed to analyze the prevalence of alcohol consumption among people living with HIV and its association with clinical outcomes. It is an analytical, cross-sectional study, carried out with people living with HIV in outpatient treatment in the municipality of Ribeirão Preto, SP. An interview was carried out using a sociodemographic instrument, a clinical instrument, and the Cuestionario para La Evaluación de La Adhesión alTratamiento Antiretroviral (Assessment of Adherence to Antiretroviral Therapy Questionnaire). Chi-squared test, Fisher's Exact Test, and logistical regression, adopting p<0.05, were used for data analysis. Of the 340 participants, the prevalence of alcohol consumption was 40.6%, of whom 35% presented low to moderate consumption and 5.6% high consumption. It was identified that people with detectable viral load have 1.76 times more chance of consuming alcohol (p=0.04; 95%CI 1.00­3.05). The study showed a high prevalence of alcohol consumption among people living with HIV and the clinical outcome presenting an association with high consumption was a viral load.

Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.

A human circulating immune cell landscape in aging and COVID-19

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.

Heterogeneity of HIV-1 latent reservoirs / 中华医学杂志(英文版)

Antiretroviral therapy (ART) can effectively inhibit human immunodeficiency virus-1 (HIV-1) replication, but is not curative due to the existence of a stable viral latent reservoir harboring replication-competent proviruses. In order to reduce or eliminate the HIV-1 latent reservoir, characteristics of the latently infected cells need to be intensively studied, and a comprehensive understanding of the heterogenous nature of the latent reservoir will be critical to develop novel therapeutic strategies. Here, we discuss the different cell types and mechanisms contributing to the complexity and heterogeneity of HIV-1 latent reservoirs, and summarize the key challenges to the development of cure strategies for acquired immunodeficiency syndrome (AIDS).