Identificación del alelo HLA B*57: 01 en una población militar, de Lima-Perú / Identification of the allele HLA B*57: 01 in a military population, from Lima-Peru

El alelo HLA B*57:01 es un marcador genético asociado con la hipersensibilidad al fármaco anti-retroviral abacavir (ABC) y su frecuencia en la población peruana todavía es desconocida. El objetivo fue identificar el alelo HLA B*57:01 en una población militar de Lima, Perú. Se reclutaron 43 personas viviendo con VIH (PVV) quienes aceptaron participar a través de un consentimiento informado. La detección del alelo HLA B*57:01 se realizó mediante RPC en tiempo real (RT-PCR). Asimismo, se determinó la carga viral (CV), el recuento de linfocitos CD4 y la genotipificación del VIH. Se identificaron dos casos positivos al alelo HLA B*57:01 (4,7%). Además, uno de ellos presentó múltiples mutaciones de resistencia a los anti-retrovirales (ARV), incluyendo ABC. Se demostró por primera vez en el Perú la presencia del alelo HLA B*57:01.

The HLA B*57:01 allele is a genetic marker associated with hypersensitivity to the antiretroviral Abacavir (ABC) and its frequency in the Peruvian population is still unknown. The objective was to identify the HLA B*57:01 allele in a military population from Lima, Peru. Forty three people living with HIV (PLWH) were recruited, who agreed to participate through informed consent. Detection of the HLA B*57:01 allele was performed by real-time PCR (RT-PCR). Likewise, viral load (VL), CD4 lymphocyte count and HIV genotyping were determined. Two cases positive for the HLA B*57:01 allele (4.7%) were identified. In addition, one of them had multiple resistance mutations to antiretrovirals (ARVs), including ABC. The presence of the HLA B*57:01 allele was demonstrated for the first time in Peru.

Effect of intensive training on immune system cells in elite female weightlifters

SUMMARY OBJECTIVE: This study aimed to investigate the effects of intense weightlifting training on lymphocyte and natural killer cell subgroups, which are the major cells of the immune system, in elite female weightlifters. METHODS: A total of 20 elite female weightlifters were evaluated using flow cytometry before training (pre-T), immediately after training (post-T), and after a 120-min rest period (rest-T). RESULTS: Post-T and rest-T showed significant decreases in helper T (Th) and cytotoxic T compared with pre-T (p=0.045, p<0.001 and p=0.05, p<0.001, respectively). B and natural killer cells were higher in post-T and rest-T than in pre-T. The increase in B cells was significant in pre-T/rest-T (p<0.001) but not in pre-T/post-T (p=0.122). Intense training significantly increased natural killer cells in both post-T and rest-T (p<0.001). CD56bright and CD56dim natural killer cell subgroups were significantly lower in post-T and rest-T than in pre-T (p=0.005, p=0.006 and p<0.001, p=0.004, respectively). CONCLUSION: This study shows that intense weightlifting alters peripheral lymphocyte and natural killer subgroup ratios, being the first investigation in this field.

Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection

ABSTRACT Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

Relationship Between Peripheral Blood T Lymphocyte Subsets and Prognosis of Patients with Advanced Non-small Cell Lung Cancer Treated with Camrelizumab / 肿瘤防治研究

Objective To explore the relationship between peripheral blood T lymphocyte subsets and prognosis of patients with advanced non-small cell lung cancer (NSCLC) who received treatment with camrelizumab. Methods We retrospectively collected data from 88 patients with advanced NSCLC who underwent camrelizumab treatment. Peripheral blood lymphocyte subsets were collected from patients before and two months after treatment. Kaplan-Meier curves and Cox regression analysis were employed to investigate the relationship between peripheral blood T lymphocyte subsets and PFS and OS. Results Compared with non-responder group, the baseline peripheral blood CD4+/CD8+ ratio was higher (P=0.038), while the CD8+T lymphocyte percentage was lower (P=0.036) in the responder group. Kaplan-Meier curves showed that a high baseline CD4+/CD8+ ratio was associated with long PFS and OS (P=0.001, P=0.023). Multivariate Cox analysis revealed that the baseline CD4+/CD8+ ratio was a significant predictor for PFS and OS. Additionally, a high post-treatment CD4+/CD8+ ratio and high CD4+T lymphocyte percentage were associated with long PFS (P=0.005, P=0.015), whereas a low post-treatment CD8+T lymphocyte percentage was associated with long PFS and OS (P=0.001, P=0.016). Conclusion The peripheral blood CD4+/CD8+ ratio can serve as a predictive factor for survival of patients with NSCLC treated with camrelizumab.

Evaluación comparativa de medición de linfocitos CD4+ por dos técnicas: estándar nacional versus test rápido de ejecución local / Comparative evaluation of CD4+ lymphocyte measurement by two techniques: national standard versus point-of-care rapid test

ANTECEDENTES: El recuento de linfocitos CD4+ (LTCD4) es una herramienta fundamental para la evaluación y seguimiento de los pacientes que viven con VIH. En Chile, la medición de LTCD4 estandarizada es por citometría de flujo. En el sistema público se realiza en forma centralizada en tres centros. Actualmente existen tecnologías de medición rápida de recuento de LTCD4 en el lugar de atención, permitiendo optimizar la atención de pacientes con infección por VIH. OBJETIVO: Comparar la precisión de un test rápido de ejecución local versus la técnica estándar. METODOLOGÍA: Realización de ambas técnicas en un grupo de 102 pacientes durante su control regular de salud. RESULTADOS: El rango de variación promedio de los resultados entre las dos técnicas fue de 10%, con una concordancia en los recuentos de LTCD4 de 97% para el rango de CD4 < 200 cél/uL, de 88% para los pacientes con recuento de LTCD4 entre 200 y 349 cél/uL y de 67% en los rangos superiores. CONCLUSIÓN: La técnica por test rápido es un sistema fácil de aplicar, de bajo costo, con alta concordancia con la técnica estándar, lo que debería considerarse en la atención de los pacientes que viven con VIH.

BACKGROUND: The CD4+ lymphocyte cell count is an instrumental tool for the assessment and follow-up in the therapeutic management of patients living with HIV. In Chile, the standardized CD4+ lymphocyte count technique is by flow cytometry. In the public health system, it is performed centralized in 3 sites. Currently, there are technologies that allow measuring the CD4 lymphocyte count at the point of care, allowing to optimize the care of HIV-infected patients. AIM: To compare the accuracy of a point of care rapid test versus the standard technique in patients under regular care at a single HIV center. RESULTS: The average variation of the results between the two techniques was 10%, with a 97% concordance in CD4 range values for patients with CD4 below 200 cells/uL, 88% for CD4 counts between 200 and 349 cells/uL. and 67% above that range. CONCLUSION: This point of care test is an easy-to-operate, low-cost system with high correlation with the standard technique and should be considered in the care of patients living with HIV.

Relación entre ansiedad, depresión y linfocitos T CD4+ en pacientes con virus de inmunodeficiencia humana (VIH) en un hospital general de Lima* / Relationship between anxiety, depression and CD4+ T lymphocytes in patients with Human Immunodeficiency Virus (HIV) in a general hospital in Lima

RESUMEN Objetivo: Determinar la relación entre ansiedad, depresión y recuento de linfocitos T CD4+ en una muestra de personas portadoras del virus de inmunodeficiencia humana (VIH). Metodología: Estudio observacional y analítico. Se evaluó a 144 pacientes con VIH en un hospital general de Lima, Perú. Se utilizó la Escala de Ansiedad y Depresión Hospitalaria (HADS). Resultados: La edad media de los sujetos de estudio fue de 41 años. La mayoría estuvo constituida por varones (71,5 %), solteros (86,1 %) y con grado de instrucción secundaria (57,6 %). La duración promedio de la enfermedad fue 7,7 años; el 11,1 % presentó alguna comorbilidad; y el 95,1 % utilizó tenofovir como tratamiento. El 34 % y el 16,7 % presentaron algún nivel de ansiedad y depresión, respectivamente. Los pacientes que se encontraban en estadio de sida presentaron mayores niveles de ansiedad (p < 0,001) y depresión (p < 0,001). Los pacientes con VIH y comorbilidades médicas presentaron mayores niveles de depresión (p = 0,044). Los niveles de ansiedad (ρ = -0,516, p = 0,01) y depresión (ρ = -0,509; p = 0,01) estuvieron relacionados con el recuento de linfocitos T CD4+. Conclusión: Se encontraron mayores niveles de depresión en pacientes con comorbilidades y estadio de sida, así como mayores niveles de ansiedad en pacientes en estadio de sida. Se comprobó, además, una relación indirecta y significativa entre los niveles de ansiedad, depresión y el recuento de linfocitos T CD4+. Se recomienda capacitar a los profesionales de salud en el tamizaje de ansiedad y depresión, a fin de mejorar la salud mental de pacientes con VIH.

ABSTRACT Objective: To determine the relationship between anxiety, depression and CD4+ T lymphocyte count in a sample of people carrying the human immunodeficiency virus (HIV). Methodology: Observational and analytical study. A total of 144 HIV-positive patients were evaluated. The Hospital Anxiety and Depression Scale (HADS) was used. Results: The sample's mean age was 41 years. Most of the probands were male (71.5%), single (86.1%) and with secondary education (57.6%). The average length of the disease was 7.7 years, 11.1% presented some comorbidity, and 95.1% used tenofovir as treatment. Thirty-four and 16.7% presented some level of anxiety and depression, respectively. Patients at the AIDS stage presented higher levels of anxiety (p < 0.001) and depression (p < 0.001). Patients with HIV and medical comorbidities had higher levels of depression (p = 0.044). Anxiety (ρ = -0.516, p = 0.01) and depression (ρ = -0.509; p = 0.01) levels were related to CD4+ T lymphocyte count. Conclusion: Higher levels of depression were found in patients with comorbidities and AIDS stage, and higher levels of anxiety were found in patients at the AIDS stage. In addition, a significant indirect relationship was found between anxiety and depression levels and the CD4+ T cell count. Training healthcare professionals to screen for anxiety and depression in order to improve the mental health of HIV patients, is highly recommended.

Impact Of Integrated Yoga Practice on Immune Parameters and Quality of Life of Adult People Living With HIV: Protocol for A Randomized Open-Label Trial in Chittoor, India

Background: Yoga therapy can be a promising adjunct to antiretroviral therapy. However, evidence on the ef-fectiveness of Yoga therapy is scanty. The proposed trial will estimate the effect of integrated yoga practice for six months on immune parameters (CD4 (cluster of differentiation 4), viral load) among adult people living with HIV (PLWH) and its cost-effectiveness from the healthcare system’s perspective. Methods: In this randomized open-label parallel-group trial, 110 PLWH in stage 2 HIV, between 18 and 49 years in the intervention arm and 220 PLWH in the same stage will be recruited by block randomization. Inte-grated yoga practice will be given for six months in the intervention arm, and health education on yoga prac-tice in the control arm, besides antiretroviral therapy. After six months, the difference in immune parameters, cardio-metabolic indicators and quality of life (QOL) will be assessed. Besides, an economic evaluation will be done with sensitivity analysis. If found useful, the intervention can be tested at large scale for further confir-mation of the outcomes. Irrespective of the study's outcome, the results will be disseminated through peer-reviewed journals.

Opportunistic infections according to the CD4+ T lymphocyte count in patients with HIV at a tertiary care referral center

Opportunistic infections (OIs) have marked the prognosis in the natural course of patients with human immunodeficiency virus (HIV) infection. Objective: identifying the most common OIs and determining their relationship with the CD4+ lymphocyte count (CD4+TL) can improve our clinical practice and facilitate early diagnosis, the use of empiric treatments and prompt targeted treatment. Materials and methods: an observational, retrospective study aimed at describing the characteristics and variations of the OIs diagnosed clinically, using direct or indirect methods, which occur in patients with HIV (related to their CD4+TL count) who are admitted to a tertiary care center in Cali, Colombia. Adult patients hospitalized from January 2018 to January 2019 with a diagnosis of HIV/AIDS and a history or current diagnosis of OI were included. Individuals under the age of 18 and pregnant women were excluded. Results: a sample of 190 patients with at least one opportunistic infection was obtained, of whom 65.3% were men with a median age of 37 years (29.0-46.0), and the rest were women with a median age of 35.5 years (31.2-43.0). Eighty-three percent had a C3 classification on admission, 86% with a CD4+TL count < 200 cells/mm3. The most frequent OIs included tuberculosis, with 28.4%, pneumocystosis with 27.9% and toxoplasmosis with 27.4%. Conclusions: in our population, despite advances in and greater availability of highly-effective antiretroviral therapy, most patients with HIV are hospitalized in advanced stages with opportunistic infections, in some cases with two or more concomitant infections, and with evidence of severe virological and immunological involvement. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2327).

Bacterial dissemination in Mycobacterium tuberculosis by CD+ T-cells & proinflammatory cytokines

Background & objectives: As CD4+ and CD8+ T lymphocyte numbers decline, the conventional, localized forms of tuberculosis shift to the atypical, disseminated forms. Variations in lymphocyte and immune cell expression levels affect how tuberculosis manifests in disseminated forms. Understanding the relationship between lymphocyte counts (CD4+ and CD8+) and pro-inflammatory cytokines such as tumour necrosis factor-alpha, interleukin-12 and interferon, we may therefore be able to shed light on how infections spread and suggest potential biomarkers for these immune factors. Methods: In this study, 15 guinea pigs were infected with Mycobacterium tuberculosis (M.tb) H37Rv strain and grouped into three groups of five each for further investigation. Serum samples and bronchoalveolar lavage (BAL) fluid were examined for the expression of pro-inflammatory cytokines and T-cell subsets in guinea pigs infected with pulmonary tuberculosis and disseminated tuberculosis. Results: We found that M.tb escapes macrophages due to pro-inflammatory cytokine dysregulation. Despite the protective immunity created by T-cells and cytokines, M.tb bacilli may spread to other organs due to inflammation induced by these immune components. A high number of T-cells and stimulated cytokine production are involved in triggering inflammation after necrotic tissue develops and tuberculosis spreads. Interpretation & conclusions: Our findings imply that increased bacilli in the spleen at the 8th wk of infection may be caused by the overexpression of CD4+ T-cell lymphocyte subsets and cytokines that generated inflammation during the 4th wk of infection. This is a pilot study with a small sample size and less assertive inference. Larger studies would be helpful to validate the results of the present investigation.

The effect of PD-1/PD-L1 signaling axis on the interaction between CD19+B cells and CD4+T cells in peripheral blood of patients with systemic lupus erythematosus

Abstract Background The defect of B cell self-tolerance and the continuous antigen presentation by T cells (TCs) mediated by autoreactive B cells (BCs) play a key role in the occurrence and development of systemic lupus erythematosus (SLE). PD-1/PD-L1 signaling axis negatively regulates the immune response of TCs after activation and maintains immune tolerance. However, the effect of PD-1/PD-L1 signaling axis on the interaction between CD19+B/CD4+TCs in the peripheral blood of patients with SLE has not been studied in detail. Methods PD-1/PD-L1 and Ki-67 levels in peripheral blood (PB) of 50 SLE patients and 41 healthy controls (HCs) were detected through flow cytometry, and then the expression of PD-1+/−cells and PD-L1+/−cells Ki-67 was further analyzed. CD19+B/CD4+TCs were separated for cell culture and the supernatant was collected to determine proliferation and differentiation of TCs. IL-10 and IFN-γ secretion in the supernatant was also determined using ELISA. Results The PD-1, PD-L1, and Ki-67 levels on CD19+B/CD4+TCs in patients with SLE were higher than HCs. In CD19+B/CD4+TCs of SLE patients, the proliferative activity of PD-L1+ cells was higher than that of PD-L1− cells, and the proliferative activity of PD-1+ cells was higher than that of PD-1− cells. In the system co-culturing CD19+B/CD4+TCs from HCs/SLE patients, activated BCs promoted TCs proliferation and PD-L1 expression among TCs. Addition of anti-PD-L1 to co-culture system restored the proliferation of TCs, and inhibited IL-10/IFN-γ level. The addition of anti-PD-L1 to co-culture system also restored Tfh and downregulated Treg in HCs. Conclusions Axis of PD-1/PD-L1 on CD19+B/CD4+TCs in PB of SLE patients is abnormal, and cell proliferation is abnormal. In CD19+B/CD4+TCs of SLE patients, the proliferative activity of PD-L1+ and PD-1+ cells compared with PD-L1− and PD-1− cells in SLE patients, respectively. CD19+B/CD4+TCs in SLE patients can interact through PD-1/PD-L1.

Tuberculosis y otras causas de morbilidad y mortalidad hospitalaria en pacientes con VIH/sida / Tuberculosis and other causes of morbidity and mortality in hospitalized patients with HIV/AIDS

Introducción: A diferencia de lo descrito en países desarrollados, en los que se informan las enfermedades crónicas no transmisibles como causa de hospitalización en pacientes con VIH, en este estudio las principales causas de admisión hospitalaria y muerte fueron las infecciones oportunistas, particularmente la tuberculosis, algo similar a lo reportado en otros países de ingresos bajos en América y África Occidental, aun con la disponibilidad de la terapia antirretroviral. Objetivos: Se determinaron las causas más frecuentes de morbilidad y mortalidad hospitalaria en pacientes con VIH. Material y métodos: Se analizaron los datos demográficos, clínicos y de laboratorio de pacientes ingresados con diagnóstico de VIH durante un año, en un hospital de Guayaquil, Ecuador. Resultados: De 151 pacientes, el 76% era del sexo masculino, con 37 años en promedio. El 56.3% conocía el diagnóstico de infección por VIH. Las principales causas de hospitalización y muerte fueron las enfermedades definitorias de sida, entre las que las formas meníngeas, como criptococosis, toxoplasmosis, sífilis y leucoencefalopatía en conjunto, siguen a la tuberculosis; el 93.5% de los fallecidos tenía recuento de CD4 menor de 200 células/mm3 (p = 0.007). Conclusión: De manera similar a lo informado en pacientes adultos jóvenes con VIH en países de bajos ingresos económicos, las infecciones oportunistas fueron la principal causa de hospitalización y muerte, relacionada con inmunosupresión intensa, estadios avanzados de la enfermedad y falta de terapia antirretroviral. Los resultados refuerzan la importancia del diagnóstico precoz y el tratamiento de la infección por VIH, así como la profilaxis de las infecciones oportunistas prevenibles.

Introduction: Unlike what has been described in developed countries where chronic non-communicable diseases are reported as the cause of hospitalization in patients with HIV, in this study the main cause of hospital admission and death were opportunistic infections, particularly tuberculosis similar to what was reported in other low-income countries in the Americas and West Africa even with the availability of antiretroviral therapy. Aim: The most frequent causes of hospital morbidity and mortality in patients with HIV were determined. Material and methods: The demographic, clinical, and laboratory data of patients admitted with a diagnosis of HIV for one year in a Guayaquil General Hospital were analyzed. Results: Of 151 patients, 76% were male with an average age of 37 years old. 56.3% knew the diagnosis of HIV infection. The main cause of hospitalization and death were AIDS-defining diseases where the meningeal forms: cryptococcosis, toxoplasmosis, syphilis and leukoencephalopathy together follow tuberculosis, and 93.5% of the deceased had a CD4 count of fewer than 200 cells/ mm3 (p = 0.007). Conclusion: Similar to what was reported in young adult patients with HIV in low-income countries, opportunistic infections were the main cause of hospitalization and death, related to severe immunosuppression, advanced stages of the disease, and without antiretroviral therapy. The results reinforce the importance of early diagnosis and treatment of HIV infection and the prophylaxis of preventable opportunistic infections.

Weight gain in patients starting Dolutegravir-based ART according to baseline CD4 count after 48 weeks of follow up

ABSTRACT Background: Excessive weight gain is a current concern among People Living with HIV (PLHIV) starting ART. Objectives: To evaluate the weight gain after 48-weeks of ART in naive patients, according with baseline CD4 count. Methods: PLHIV starting 3TC + TDF + DTG with at least 48-weeks of follow up in two AIDS referral centers were stratified by baseline CD4 count (lower or higher than 200 cells/mm3). Data on CD4 count, HIV viral load, weight/Body Mass Index (BMI), lipids and glucose levels were collected at baseline, 24 and 48 weeks of treatment. For analysis purpose, patients were categorized according to their BMI progression. Results: A total of 270 patients were included in the study. Mean CD4 count were 78.3 ± 61.7 and 536.7 ± 273 cells/mm3 for low and high CD4 count groups, respectively (p < 0.001). Baseline BMI was significantly lower in low CD4 group (21.7 vs. 23.6 Kg/m2, p < 0.001). Patients in low CD4 group gained more weight than those in high CD4 group (11.2 ± 8.5 kg vs. 2.2 ± 4.2 Kg, p = 0.004). Overall weight gain was higher in women, regardless group (13.1 ± 7.9 Kg vs. 1.4 ± 3.6 Kg for women and men, respectively, p < 0.001). The proportion of overweight/obesity significantly increased in low CD4 group. Viral suppression rate was high for both groups. At week 48 the overall proportion of overweight/obesity was like that reported for the Brazilian population. Conclusions: Weight gain in the present study indicates a "return to health" phenomenon. Excessive weight gain was more frequent in women.

Recuento de linfocitos CD4, carga viral y colonización oral por Candida en personas viviendo con VIH/SIDA

Objetivos: determinar la correlación entre el recuento de CD4, carga viral y la colonización oral por Candida en personas viviendo con VIH/SIDA (PVVS) que reciben terapia antirretroviral (TAR). Métodos: se realizó un estudio transversal correlacional con 35 participantes que recibían tratamiento antirretroviral. Mediante citometría de flujo se determinó el recuento de CD4; la carga viral se determinó mediante RT-PCRq y la confirmación de colonización oral se realizó mediante aislamiento de Candida spp. Resultados: el recuento de CD4 se correlacionó significativamente de manera inversa con la carga viral (rho de Spearman = -0,457, p=0,006; Kendall Tau-b= -0,306, p=0,012) y con la colonización oral por Candida (rho de Spearman = -0,442, p=0,008; Kendall Tau-b= -0,366, p=0,010), no se encontró significancia estadística entre la carga viral y colonización (p>0,05). Conclusiones: En las PVVS que reciben TAR, los recuentos bajos de CD4 se relacionan con mayor colonización oral por Candida, no se encontró asociación de dicha colonización con la carga viral.

Objectives: to determine the correlation between CD4 count, viral load, and oral Candida colonization in people living with HIV/AIDS (PLWHA) receiving antiretroviral therapy (ART). Methods: a correlational cross-sectional study was conducted with 35 participants receiving antiretroviral treatment. Using flow cytometry, the CD4 count was determined; the viral load was determined by RT-PCRq and confirmation of oral colonization was made by isolating Candida spp. Results: CD4 count was significantly inversely correlated with viral load (Spearman's rho = -0.457, p=0.006; Kendall Tau-b= -0.306, p=0.012) and with oral Candida colonization (Spearman's rho = -0.442, p=0.008; Kendall Tau-b= -0.366, p=0,010), no statistical significance was found between viral load and colonization (p>0.05). Conclusions: in PLWHA receiving ART, low CD4 counts are associated with greater oral colonization by Candida; no association of said colonization with viral load was found.

Effect of propolis on Th2 and Th17 cells: interplay with EtxB- and LPS-treated dendritic cells

Dendritic cells (DCs) are antigen-presenting cells that drive the differentiation of T CD4+ cells into different profiles according to the nature of the antigen or immunomodulator. Propolis is a resinous product made by bees that has numerous pharmacological properties, including an immunomodulatory action. To assess whether propolis can modulate the activation of CD4+ T cells by stimulating DCs with heat-labile enterotoxin B subunit (EtxB) or lipopolysaccharide (LPS), we aimed to elucidate the mechanisms affected by propolis in the differential activation of T lymphocytes. Cell viability, lymphocyte proliferation, gene expression (GATA-3 and RORc), and cytokine production (interleukin (IL)-4 and IL-17A) were analyzed. Propolis, EtxB, and LPS induced a higher lymphoproliferation compared with the control. Propolis induced GATA-3 expression and, in combination with EtxB, maintained the baseline levels. Propolis alone or in combination with LPS inhibited RORc expression. EtxB alone and in combination with propolis increased IL-4 production. Propolis in combination with LPS prevented LPS-induced IL-17A production. These results opened perspectives for the study of biological events that may be favored by propolis by promoting Th2 activation or helping in the treatment of inflammatory conditions mediated by Th17 cells.

Diagnostic and prognostic value of peripheral blood CD4+T lymphocytes for hepatocellular carcinoma recurrence after liver transplantation / 中华检验医学杂志

Objective:To investigate the clinical value of peripheral blood T lymphocytes in the diagnosis and prognosis of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation.Methods:The clinical and laboratory data of 50 HCC patients, who received liver transplantation and were followed up in the Liver transplantation Center of Beijing Youan Hospital from January 2014 to December 2016, were retrospectively analyzed. The differences on clinical laboratory indicators and five-year survival were compared between HCC recurrence group ( n=29) and non-recurrence group ( n=21). Spearman correlate analysis was used to analyze the correlation between clinical laboratory indicators and HCC recurrence after liver transplantation. Receiver operator characteristic (ROC) curve was used to analyze the diagnostic value of CD4+T lymphocytes in HCC recurrence after liver transplantation. Kaplan-Meier survival curve was used to compare the survival time of patients with different CD4+T lymphocytes levels post liver transplantation. Results:Compared to non-recurrence group, the level of alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, albumin, lymphocytes, alpha-fetoprotein, protein induced by vitamin K deficiency or antagonist-Ⅱ, CD3+, CD4+and CD8+T lymphocytes were significantly different (all P<0.05). The median recurrence time after liver transplantation was 13.0 (6.0, 24.0) months, and the mortality rate was 100%. The 5-year mortality rate was 0 in the non-recurrence group. During 5-year follow-up, the median survival time of patients in the HCC recurrence group was 18.0 (9.0, 36.0) months, which was significantly lower than that of non-recurrence group [60.0 (60.0, 60.0) months, ( P<0.05)]. Compared with non-recurrence group, the CD3+, CD4+, and CD8+T lymphocytes were significantly lower in the recurrence group (all P<0.05). Spearman correlate analysis showed that HCC recurrence after liver transplantation was negatively correlated with the CD3+, CD8+and CD4+T lymphocytes ( r=-0.43, -0.38, -0.44, all P<0.05). ROC analysis showed that CD4+T lymphocytes at cutoff of≤265.50 cells/μl was valuable for the diagnosis of HCC recurrence after liver transplantation (specificity 100%, sensitivity 48.30%). Survival curve analysis showed that the survival time was significantly lower in the CD4≤265.50 cells/μl group [15.0 (10.0, 36.8) months] than that in the CD4>265.50 cells/μl group [53.0 (19.5, 60.0) months] ( P<0.05). Conclusion:There is a significant negative correlation between CD4+T lymphocytes and HCC recurrence after liver transplantation. CD4+T lymphocytes at cutoff value of≤265.50 cells/μl is valuable for the clinical diagnosis and prognosis evaluation of HCC recurrence after liver transplantation.

miR-146a downregulates epidermal Langerhans cell-mediated antigen presentation / 中华微生物学和免疫学杂志

Objective:To investigate the role of miR-146a in regulating the homeostasis and function of epidermal Langerhans cells (LCs).Methods:Fresh and in vitro cultured epidermal LCs were isolated and purified by flow cytometry (FCM). The expression of miR-146a in LCs was detected by quantitative PCR (qPCR). The percentages of epidermal LCs in wild-type (WT) and miR-146a conventional knockout (miR-146a cKO) mice were analyzed by FCM. The expression of major histocompatibility complex Ⅱ (MHCⅡ) and co-stimulatory molecules (CD86 and CD80) was analyzed by FCM to evaluate the effect of miR-146a on the maturation of LCs. The percentage of Dextran-FITC + LCs was detected by FCM to evaluate the effect of miR-146a on the phagocytic function of LCs. In vitro and in vivo experiments were used to analyze the ability of miR-146a-deficient and -sufficient LCs to stimulate the proliferation of CD8 + OT-ⅠT cells and CD4 + OT-Ⅱ T cells. Results:The expression of miR-146a was significantly increased in mature LCs than in the freshly isolated LCs. There was no significant difference in the number of epidermal LCs between wild-type (WT) and miR-146a cKO mice. After a 48 h culture in vitro, the expression of MHCⅡ, CD86 and CD80 in the epidermal LCs of miR-146a cKO mice was similar to that of WT mice. Moreover, miR-146a deletion had no significant influence on antigen uptake by LCs. However, miR-146a deficiency enhanced the antigen-presenting ability of LCs that could stimulate the proliferation of OVA-specific CD8 + OT-Ⅰ T cells and CD4 + OT-Ⅱ T cells. Conclusions:miR-146a had no influence on the homeostasis, maturation and phagocytosis of LCs, but enhanced the antigen-presenting function.

Study on the relationship between intestinal flora analysis and CD4 +T lymphocyte subsets in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To explore the characteristics of intestinal microbiota in patients with systemic lupus erythematosus (SLE), and further explore the relationship between microbiota and CD4 +T lymphocyte subsets and disease activity. Methods:Fecal samples were collected from 96 patients with SLE, and 96 sex- and age-matched healthy controls (HCs). The gut microbiota were investigated via 16s rRNA sequencing. Flow cytometry was used to detect peripheral CD4 +T lymphocyte subsets of Th1, Th2, Th17 and Treg cells. Indicators of disease activity such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3 and C4, Systemic lupus erythematosus disease activity index(SLEDAI) for each patient were recorded. Differential abundance analysis was carried out using the edgeR algorithm. The Wilcoxon rank-sum test was used to compare alpha diversity indices, bacterial abundances, and the F/B ratio between groups. R (version 4.0.1) was used for comparative statistics, and Pearson′s correlation analysis was used to assess the correlations between the relative abundances of bacterial genera and serum levels of ESR, CRP, C3 and C4 in the samples. Results:The alpha estimators of richness (ACE and Chao 1) were significantly reduced in SLE feces samples compared with those of HCs ( P<0.01). Bacterial diversity estimators, including the Shannon ( P<0.01) and Simpson′s ( P<0.01) indices, were also significantly lower in SLE. Significant differences in gut microbiota composition between SLE and HCs were found using the edgeR algorithm. Compared with HC, 24 species of bacteria were significantly different in SLE patients at the genus level ( P<0.05). Moreover, there was a significant positive correlation between CRP and Coprococcus ( r=0.30, P=0.014), C4 and Corynebacterium ( r=0.31, P=0.013) and Faecalibacterium( r=0.25, P=0.048), Hemoglobin and Morganella( r=0.41, P=0.001), as well as SLIDA and Corynebacterium( r=0.25, P=0.047). In terms of lymphocyte subsets, there was significant positive correlation between B cells, Treg cells and Eubacterium eligens group, as well as CD8 +T, CD4 +T, NK cells and Corynebacterium. In additional, Th1 was positively correlated with Shigella Escherichia coli ( r=0.52, P=0.008), and Th2 was positively correlated with Dielma ( r=0.51, P<0.001). Conclusion:The abundance and diversity of intestinal flora in SLE patients were significantly reduced, and the differentially expressed bacteria were closely related to the CD4 +T lymphocyte subsets and disease activity indicators of patients.

Investigation on the incidence of IRIS in HIV patients with TB infection and its relationship with Th17/Treg, CD4 + T lymphocyte levels / 中国医师杂志

Objective:To investigate the incidence of immune reconstitution inflammatory syndrome (IRIS) in patients with HIV (HIV) and tuberculosis (TB) infection, and analyze the relationship between Th17/Treg cytokines, CD4 + T lymphocytes and IRIS. Methods:HIV patients with TB infection admitted to Public Health Clinical Center of Chengdu from June 2020 to June 2022 were divided into IRIS group (31 cases) and non IRIS group (93 cases) according to whether IRIS occurred after highly active antiretroviral therapy (HAART). The Demography data, clinical data and laboratory indicators of the two groups were compared. Multivariate logistic regression analysis was conducted to investigate the influencing factors of IRIS in HIV patients with TB infection.Results:There was no significant difference in Demography data between the two groups ( P>0.05). There was a statistically significant difference in the history of opportunistic infection between the IRIS group and the non IRIS group (χ 2=5.194, P<0.05). The levels of HIV RNA, interleukin (IL)-17, and IL-23 in the IRIS group were higher than those in the non IRIS group (all P<0.05). The levels of the γ interferon (IFN- γ), the transforming growth factor-β (TGF- β) and baseline CD4 + T lymphocyte count were lower than those in the non IRIS group (all P<0.05). The results of multivariate logistic regression analysis showed that IL-17 ( OR: 1.266, 95% CI: 1.095-1.464), IL-23( OR: 1.384, 95% CI: 1.120-1.710), and TGF- β( OR: 0.589, 95% CI: 0.436-0.797) were influencing factors for the occurrence of IRIS in HIV patients with TB infection (all P<0.05). Conclusions:For patients with high IL-17 levels, high IL-23 levels, and low TGF- β level of HIV complicated with TB infection, clinical prevention and control should be carried out as soon as possible to prevent the occurrence of IRIS.

Value of bedside high-flow continuous blood purificationcombined with Xuebijing in the treatment of severe sepsis / 中国医师进修杂志

Objective:To investigate the effect of bedside high-flow continuous blood purification (CBP) combined with Xuebijing in the treatment of severe sepsis (SS) and the influence on the patient′s coagulation-fibrinolysis index, immunity index and expression of peripheral blood Toll-like receptor 4 (TLR4).Methods:Ninety-three patients with SS who were admitted and treated in the Lianyungang First People′s Hospitalfrom January 2017 to October 2019 were selected. They were divided into the combined group (51 cases, treatment with bedside high-flow CBP and Xuebijing injection based on bundle therapy) and the control group (42 cases, treatment with Xuebijing injection based on bundle therapy). The changes in coagulation and fibrinolysis index, immunity index, biochemical index such as TLR4 before treatment and after 1 week of treatment were compared between the two groups. The incidences of complications in both groups were statistically analyzed, and the discharge time from ICU, mechanical ventilation time and 28-day mortality were recorded.Results:After 1 week of treatment, the levels of prothrombin time (PT) and activated partial thromboplastin time (APTT) in the two groups were shortened, D-dimer (D-D) and fibrinogen (FIB) were decreased ( P<0.05); and the levels of PT and APTT in the combined group were shorter than those in the control group, the levels of DD and FIB were lower than those in the control group, there were statistical differences ( P<0.05). After 1 week of treatment, the levels of CD 4+ and CD 4+/CD 8+ ratio in both groups were increased ( P<0.05), and the levels of CD 4+ and CD 4+/CD 8+ ratio in the combined group were higher than those in the control group ( P<0.05). After 1 week of treatment, the levels of TLR4, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), blood lactate (Lac), blood urea nitrogen (BUN) and serum creatinine (Scr) in both groups were decreased ( P<0.05), meanwhile, the above indexes in the combined group were lower than those in the control group ( P<0.05). The incidence of multiple organ failure and the 28-day mortality rate in the combined group were lower than those in the control group: 3.92%(2/51) vs. 19.05%(8/42), 13.73%(7/51) vs. 30.95%(13/42), there were statistical differences ( P<0.05). The discharge time from ICU and mechanical ventilation time in the combined group were shorter than those in the control group: (12.35 ± 2.14) d vs. (14.17 ± 3.36) d, (7.12 ± 2.23) d vs. (8.51 ± 2.39) d, there were statistical differences ( P<0.05). Conclusions:Bedside high-flow CBP combined with Xuebijing injection in the treatment of SS can improve the patient′s condition, regulate the balance of coagulation and fibrinolysis, avoide the activation of coagulation, inhibite inflammatory response, reduce the expression of TLR4 in peripheral blood, improve immune function, protecte kidney function and promotethe patient′s recovery.

Analysis of the first measurement of CD4+T lymphocyte cell counts of newly reported HIV/AIDS cases in Taizhou City from 2012 to 2021 / 预防医学

Objective@#To investigate the level and timeliness of CD4+T lymphocyte cell (CD4 cell) counts at first measurement among newly reported HIV/AIDS cases in Taizhou City, Zhejiang Province from 2012 to 2021, so as to provide insights into improving the management of HIV/AIDS cases. @*Methods@#Demographic data and first measurement of CD4 cell counts of newly reported HIV/AIDS cases in Taizhou City from 2012 to 2021 were collected from the HIV/AIDS Comprehensive Control System of Chinese Disease Prevention and Control Information System. The level and time of CD4 cell counts at first measurement were descriptively analyzed, and factors affecting CD4 cell counts at first measurement were identified using a multivariable logistic regression model. @*Results@#A total of 4 834 newly reported HIV/AIDS cases were recorded in Taizhou City from 2012 to 2021, including 3 889 men (80.45%), 2 005 cases at ages of 20 to 39 years (41.48%), and 2 130 farmers (44.06%). There were 1 664 cases (34.42%) with CD4 cell counts of <200/mm3 at first detection, 2 576 (53.29%) with CD4 cell counts of 200/mm3 to 499/mm3, and 594 (12.29%) with CD4 cell counts of ≥500/mm3. The proportion of CD4 cell counts of <200/mm3 showed a tendency towards a rise from 2012 to 2021 (χ2trend =4.250, P<0.001). There were 3 465 cases (71.68%) that had an interval of ≤14 days between the first detection of CD4 cell counts and confirmatory HIV test, 740 (15.31%) that had an interval of >14 to 30 days, 315 (6.52%) that had an interval of >30 to 90 days, 135 (2.79%) that had an interval of >90 to 180 days, and 179 (3.70%) that had an interval of >180 days. The proportion of an interval of ≤14 days appeared a tendency towards a rise from 2012 to 2021 (χ2trend=6.874, P<0.001). Multivariable logistic regression analysis identified women (OR=0.630, 95%CI: 0.529-0.751), age of ≥20 years (OR: 1.958 to 3.218, 95%CI: 1.216-5.412), other or unknown routes of HIV infection (OR=1.785, 95%CI: 1.100-2.896), and identification by medical institutions (OR=1.779, 95%CI: 1.497-2.114) as factors affecting CD4 cell counts of <200/mm3 at first measurement. @*Conclusions@#The timely detection of CD4 cell counts at first measurement gradually increased with year among newly reported HIV/AIDS cases in Taizhou City from 2012 to 2021; however, there were still 34.42% of cases with CD4 cell counts of <200/mm3. Gender, age, route of HIV infection, and sample source were factors affecting CD4 cell counts of <200/mm3 at first measurement.