RESUMEN
Around half of people with severe COVID-19 requiring intensive care unit (ICU) treatment will survive, but it is unclear how the immune response to SARS-CoV-2 differs between ICU patients that recover and those that do not. We conducted whole-blood immunophenotyping of COVID-19 patients upon admission to ICU and during their treatment and uncovered marked differences in their circulating immune cell subsets. At admission, patients who later succumbed to COVID-19 had significantly lower frequencies of all memory CD8+ T cell subsets, resulting in increased CD4-to-CD8 T cell and neutrophil-to-CD8 T cell ratios. ROC and Kaplan-Meier analyses demonstrated that both CD4-to-CD8 and neutrophil-to-CD8 ratios at admission were strong predictors of in-ICU mortality. Therefore, we propose the use of the CD4-to-CD8 T cell ratio as a marker for the early identification of those individuals likely to require enhanced monitoring and/or pro-active intervention in ICU.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , COVID-19/inmunología , Anciano , Relación CD4-CD8/métodos , Femenino , Humanos , Inmunofenotipificación/métodos , Unidades de Cuidados Intensivos , Recuento de Linfocitos/métodos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2/inmunologíaRESUMEN
Ageing dramatically affects number and function of both innate and adaptive arms of immune system, particularly T cell subsets, contributing to reduced vaccination efficacy, decreased resistance to infections and increased prevalence of cancer in older people. In the present paper, we analysed the age-related changes in the absolute number of lymphocytes in 214 Sicilian subjects, and in the percentages of T and natural killer (NK) cells in a subcohort of donors. We compared these results with the immunophenotype of the oldest living Italian supercentenarian (aged 111 years). The results were also sorted by gender. The correlation between number/percentage of cells and age in all individuals. and separately in males and females, was examined using a simple linear regression analysis. We did not record the increase in the rate of inversion of the CD4/CD8 ratio, frequently reported as being associated with ageing in literature. Our observation was the direct consequence of a flat average trend of CD4+ and CD8+ T cell percentages in ageing donors, even when gender differences were included. Our results also suggest that CD4+ and CD8+ subsets are not affected equally by age comparing females with males, and we speculated that gender may affect the response to cytomegalovirus (CMV) infection. The supercentenarian showed a unique immunophenotypic signature regarding the relative percentages of her T cell subsets, with CD4+ and CD8+ T cell percentages and CD4+ naive T cell values in line with those recorded for the octogenarian subjects. This suggests that the supercentenarian has a naive 'younger' T cell profile comparable to that of a >80-year-old female.
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Envejecimiento/inmunología , Células Asesinas Naturales/inmunología , Subgrupos de Linfocitos T/inmunología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Relación CD4-CD8/métodos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/inmunología , Femenino , Identidad de Género , Humanos , Inmunofenotipificación/métodos , Masculino , Persona de Mediana Edad , SiciliaRESUMEN
BACKGROUND: Sarcoidosis is diagnosed by a combination of typical clinical and radiological findings together with biopsy proof of non-caseating epithelioid cell granulomas in affected tissues and/or the cell distribution in bronchoalveolar lavage fluid (BALF). We aimed at investigating the usefulness of measuring the proportion of T-cell receptor (TCR) CD4+ Vα2.3+ T-cells in BALF as an additive marker to CD4/CD8-ratio to confirm the diagnosis. METHODS: From a register consisting of 749 sarcoidosis patients [Löfgren's syndrome (LS) n = 274, non-LS n = 475] with information on Vα2.3+ T-cells, an expansion of CD4+ Vα2.3+ T-cells (CD4+ Vα2.3+ T cells > 10.5% in BALF) was seen in 268 (36%). Controls were healthy volunteers (n = 69) and patients with other pulmonary conditions (n = 39), investigated because of suspicion of sarcoidosis. RESULTS: A proportion of CD4+ Vα2.3+ T-cells in BALF > 10.5% was highly specific for sarcoidosis, with a specificity of 97% and with a sensitivity of 36% (p < 0.0001). Receiver operating characteristic (ROC) curves show that testing for CD4+ Vα2.3+ T-cells in BALF was a more useable test in individuals with LS [area under the curve (AUC) 0.82, p < 0.0001] compared to the whole patient group (AUC 0.64, p < 0.0001). CONCLUSION: In this study, we show that an increased proportion of CD4+ Vα2.3+ T-cells in BALF is highly specific for sarcoidosis. This suggests that this T-cell subset could be used as an additional tool to the CD4/CD8-ratio to support the sarcoidosis diagnosis, particularly in patients with LS but also in patients with non-LS.
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Linfocitos T CD4-Positivos/metabolismo , Pulmón/metabolismo , Sarcoidosis Pulmonar/diagnóstico , Sarcoidosis Pulmonar/metabolismo , Adolescente , Adulto , Anciano , Líquido del Lavado Bronquioalveolar , Broncoscopía/métodos , Relación CD4-CD8/métodos , Linfocitos T CD4-Positivos/patología , Estudios de Cohortes , Femenino , Humanos , Pulmón/patología , Masculino , Persona de Mediana Edad , Sarcoidosis Pulmonar/patología , Adulto JovenRESUMEN
BACKGROUND: The incidence of cryptococcal meningitis (CM) has gradually increased in recent years. Cerebrospinal fluid (CSF) cytology and cell count are very important for CM on etiology diagnosis and assessment of disease status and therapeutic response. However, the clinical significance of CSF white cell count (WCC) in CM patients is not fully understood. Using longitudinal data of CSF WCC and its relationship with clinical outcomes in CM patients, we aimed to elucidate the clinical significance of this test. METHODS: We retrospectively analyzed the medical records of 150 CM patients admitted to our hospital between January 2008 and December 2018. RESULTS: CM patients with lower baseline CSF WCC, CSF protein concentration or CD4/CD8 ratio, and those with altered mentation or HIV coinfection were more likely to have poor clinical outcome (P<0.05). CM patients with triple therapy during the induction period presented with a better clinical outcome (P<0.05). Baseline CSF WCC had a moderate positive correlation with peripheral CD4+ T lymphocyte count (r = 0.738, P < 0.001) and CD4+ T lymphocyte percentage (r = 0.616, P < 0.001). The best cut-off value to predict a poor clinical outcome was 40 cells/µL during baseline CSF WCC. The predictive model incorporating longitudinal data of CSF WCC had better sensitivity, specificity, and accuracy than a model incorporating only baseline CSF WCC data. CONCLUSIONS: Our results indicated that baseline CSF WCC and changes in CSF WCC over time could be used to assess the prognosis of CM patients.
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Relación CD4-CD8/métodos , Cryptococcus neoformans , Meningitis Criptocócica/líquido cefalorraquídeo , Meningitis Criptocócica/diagnóstico , Adulto , Antirretrovirales/uso terapéutico , Antifúngicos/uso terapéutico , China , Exactitud de los Datos , Femenino , Predicción/métodos , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Estudios Longitudinales , Masculino , Meningitis Criptocócica/tratamiento farmacológico , Meningitis Criptocócica/microbiología , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
Hepatitis C virus (HCV) coinfection is a strong risk factor for death of HIV-infected patients. Immune dysfunction affects the clinical course of acute hepatitis C (AHC). CD4/CD8 ratio is a biomarker of both persistent inflammation and immunosenescence in HIV-infected adults on effective antiretroviral therapy. A low CD4/CD8 ratio predicts immunosenescence and is associated with increased morbidity and mortality in both HIV-infected adults and elderly HIV-uninfected adults. Additionally, immunosenescence is associated with unresponsiveness to vaccine and could affect the immune reaction to pathogens during their primary infection. We retrospectively evaluated 12 AHC patients to assess the association between CD4/CD8 ratio and liver damage in AHC. We used the Spearman rank correlation test to assess the correlation. We found that CD4/CD8 ratio and peak alanine aminotransferase level (peak ALT) were positively correlated (r = 0.8322, p = 0.0013). The CD4 counts did not correlate with peak ALT (r = 0.5245, p = 0.0839). CD8+ T cells expansion for AHC did not affect these results, because the CD4/CD8 ratio before the onset of AHC and peak ALT positively correlate (n = 11; r = 0.7909, p = 0.0055) and there was no significant difference between CD4/CD8 ratios before and after the onset of AHC (n = 11; p = 0.9766). Immunosenescence may be negatively associated with the cellular immune response to acute HCV infection. We suggest that clinicians consider using CD4/CD8 ratio as a marker of immunosenescence in their management of patients with HIV infection and other complications.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/inmunología , VIH/inmunología , Hepacivirus/inmunología , Hepatitis C/inmunología , Inmunidad Celular/inmunología , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Relación CD4-CD8/métodos , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Carga Viral/inmunologíaRESUMEN
BACKGROUND: Cigarette smoke (CS) exerts protective effect against ulcerative colitis. The mechanism of this phenomenon remains unknown. One of the possible explanation by which CS exerts its anti-inflammatory action is modulation of immune system. Therefore, the aim of the study was to evaluate the effect of CS on the course of inflammation and subpopulations of lymphocytes in the blood and colon in mice with dextran sulfate sodium (DSS)-induced colitis. METHODS: C57BL6/cmdb mice were exposed to CS for 4 weeks. Colitis was induced with 3.5% DSS given for 10 days. Severity of colitis was determined by disease activity index (DAI), body weight changes, and macro- and microscopic characteristics of inflammation. Peripheral subpopulations of lymphocytes were assessed by flow cytometry (blood) or immunohistochemistry (colonic tissue). RESULTS: Mice treated with 3.5% DSS developed severe colitis with significantly decreased body weight, increased DAI, and macroscopic and histological features of colonic inflammation. These findings were diminished after concomitant exposure to CS. Mice exposed to DSS alone demonstrated significantly decreased percentage of total CD4+ cells (73.1 vs. 52%, p = 0.0007), accompanied by increase of CD8+ cells (18.4 vs. 39.5%, p = 0.0001). Concomitant CS exposure reversed inappropriate CD4+/CD8+ ratio both in the blood and colon and significantly increased B cell presence in the colon. CONCLUSIONS: Our study has demonstrated that CS exposure decreases severity of DSS-induced colitis. This phenomenon was accompanied by changes in CD4/CD8 ratio and B cell level in the peripheral blood and colon. These mechanisms may be responsible for protective effect of smoking in ulcerative colitis.
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Fumar Cigarrillos/fisiología , Colitis Ulcerosa , Sulfato de Dextran/farmacología , Animales , Relación CD4-CD8/métodos , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/patología , Colitis Ulcerosa/prevención & control , Colon/efectos de los fármacos , Colon/inmunología , Colon/patología , Modelos Animales de Enfermedad , Factores Inmunológicos/farmacología , Subgrupos Linfocitarios/efectos de los fármacos , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/patología , Ratones , Factores Protectores , Índice de Severidad de la EnfermedadRESUMEN
After a diagnosis of HIV infection is made, the patient needs to be monitored using both clinical assessment and laboratory markers. HIV/AIDS monitoring is essential in guiding when to recommend initiation of therapy. Clinical monitoring will include staging of the HIV/AIDS disease using either the presence or absence of HIV-related signs and symptoms using the WHO staging system. Various laboratory methods can be used to monitor the disease progression and to guide whether the patient will need antiretroviral therapy or not. Laboratory monitoring for patients who are not on drugs is done to provide information about the stage of illness; to enable the clinician to make decisions on treatment and to give information on prognosis of the patient. Patients on drugs are monitored to assess their response to treatment with antiretroviral drugs and to detect any possible toxicity and improvement associated with the antiretroviral drugs.
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Relación CD4-CD8/métodos , Países Desarrollados , Citometría de Flujo/métodos , Infecciones por VIH/diagnóstico , VIH-1/genética , Garantía de la Calidad de Atención de Salud/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Carga Viral/métodos , Factores de Edad , Terapia Antirretroviral Altamente Activa/métodos , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Pronóstico , Factores SexualesRESUMEN
OBJECTIVES: We aimed to evaluate the immune response of HIV-1 positive patients to a single injection of HAV vaccine in a context of vaccine shortage during the 2017 European outbreak. METHODS: We retrospectively enrolled all HIV-1 positive patients vaccinated by a single injection of HAV vaccine Vaqta 50®. HAV serology was performed before and>30 days after the vaccine injection. RESULTS: Among the 73 patients, HIV-1 viral load was≤50 copies/mL in 93.2% of the cases. Medians of CD4 and median ratio of T CD4/CD8 cells were 658/mm3 and 0.9, respectively. A low immune response rate (59.7%) was observed among the patients. Responders had a significantly higher CD4/CD8 cell ratio than non-responders. CONCLUSIONS: A serologic control should be recommended in this population in the event of a single injection vaccination schedule. During routine follow-up, and prior to any untoward event, physicians should assess the vaccination coverage of HIV-infected patients.
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Infecciones por VIH/inmunología , Vacunas contra la Hepatitis A/inmunología , Hepatitis A/prevención & control , Adulto , Recuento de Linfocito CD4/métodos , Relación CD4-CD8/métodos , Brotes de Enfermedades , Hepatitis A/epidemiología , Hepatitis A/inmunología , Anticuerpos de Hepatitis A/sangre , Vacunas contra la Hepatitis A/administración & dosificación , Humanos , Inmunidad/inmunología , Esquemas de Inmunización , Persona de Mediana Edad , Estudios Retrospectivos , Carga ViralRESUMEN
Low CD4+ cell count in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection during combination antiretroviral therapy (cART) has been described; however, notably few studies have investigated coinfected patients positive for antibodies to the HBV c antigen (HBcAb). An observational retrospective study enrolling 190 patients was conducted by grouping patients with respect to HBV status and recording CD4+ T cell counts and percentages (CD4%), CD8+ T cell counts and percentages (CD8%), and the CD4+ to CD8+ T cell ratio (CD4/CD8) at the time of HIV diagnosis, at the start of treatment and at months 1, 2, 3, 4, 5, 6, 12, and 24 after beginning cART. One hundred and twenty patients (63.2%) were negative for previous HBV infection, while 70 (36.8%) were HBcAb-positive. A significant increase in the CD4/CD8 ratio was recorded in HIV monoinfected subjects compared to HBV coinfected patients from months 4 to 12 from the beginning of cART (p value = 0.02 at month 4, p value = 0.005 at month 5, p value = 0.006 at month 6, and p value = 0.008 at month 12). A significant increase in the absolute count of CD8+ T lymphocytes was described from months 2 to 24 from the start of cART in the subgroup of HBV coinfected patients with an AIDS event at the onset of HIV infection. The presence of HBcAb was observed to be associated with reduced CD4/CD8 ratio growth and a significantly higher proportion of subjects with CD4/CD8 < 0.45 in the HIV/HBV coinfected group. A significant increase in the CD8 T cell count was shown up to 24 months after the initiation of effective cART in the subgroup of patients with the worst immune status.
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Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/inmunología , Hepatitis B/inmunología , Adulto , Recuento de Linfocito CD4/métodos , Relación CD4-CD8/métodos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Coinfección/inmunología , Coinfección/virología , Femenino , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , VIH-1/metabolismo , VIH-1/patogenicidad , Hepatitis B/virología , Anticuerpos contra la Hepatitis B/inmunología , Virus de la Hepatitis B/metabolismo , Virus de la Hepatitis B/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Carga ViralRESUMEN
Lymphocyte subsets enumeration is of paramount importance in the management of immunodeficiency disorders such as HIV/AIDS. For better interpretation of laboratory findings, reference intervals must be determined in each population. Because of scarcity of published studies from Iranian population, lymphocyte subsets were enumerated in 142 healthy Iranian men by a single platform flow cytometric method. Mean and 95% confidence interval for CD4+ T cells, CD8+ T cells, CD4/CD8 ratio, B cells, and natural killer cells were 748.8 (351-1207), 409.0 (192-752), 1.96 (0.77-3.70), 238.6 (82-500), and 200.7 (91-393), respectively. We compared our results with other studies and found significant differences with some of them. In conclusion, we endorse determination of lymphocyte subsets reference interval in different populations.
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Citometría de Flujo/métodos , Infecciones por VIH/diagnóstico , Subgrupos Linfocitarios/citología , Adulto , Subgrupos de Linfocitos B/citología , Relación CD4-CD8/instrumentación , Relación CD4-CD8/métodos , Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/citología , Citometría de Flujo/instrumentación , Infecciones por VIH/inmunología , Humanos , Irán , Células Asesinas Naturales/citología , Masculino , Valores de Referencia , Subgrupos de Linfocitos T/citologíaRESUMEN
Advances have been made in minimally invasive diagnostic procedures in sarcoidosis, including bronchoalveolar lavage (BAL), endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA), and positron emission tomography (PET). Several independent groups found almost identical predictive values of the CD4:CD8 ratio in BAL for the diagnosis of sarcoidosis. A CD4:CD8 ratio greater than 3.5 shows a high specificity of 93 to 96% for sarcoidosis, but the sensitivity is low (53 to 59%). EBUS-TBNA is a safe and useful tool for diagnosing sarcoidosis stage I and II with a sensitivity of 83 to 93% and a specificity of 100%. Novel imaging techniques have been explored, such as PET using L-[3- (18)F] fluoro-alpha-methyltyrosine ( (18)F-F MT), which is more specific for malignancy than (18)F-fluorodeoxyglucose ( (18)F-FDG)-PET. The combined modality of FMT-PET with FDG-PET could successfully discriminate sarcoidosis from malignancy. These recent developments including novel biopsy procedures and novel imaging techniques could be of value to diagnosing sarcoidosis.
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Relación CD4-CD8/métodos , Tomografía de Emisión de Positrones/métodos , Sarcoidosis/diagnóstico , Biopsia con Aguja/métodos , Lavado Broncoalveolar/métodos , Humanos , Valor Predictivo de las Pruebas , Sarcoidosis/patología , Sensibilidad y Especificidad , Ultrasonografía Intervencional/métodosRESUMEN
Background: A previously proposed immune risk profile (IRP), based on T cell phenotype and CMV serotype, is associated with mortality in the elderly and increased infections post-kidney transplant. To evaluate if NK cells contribute to the IRP and if the IRP can be predicted by a clinical T cell functional assays, we conducted a cross sectional study in renal transplant candidates to determine the incidence of IRP and its association with specific NK cell characteristics and ImmuKnow® value. Material and Methods: Sixty five subjects were enrolled in 5 cohorts designated by age and dialysis status. We determined T and NK cell phenotypes by flow cytometry and analyzed multiple factors contributing to IRP. Results: We identified 14 IRP+ [CMV seropositivity and CD4/CD8 ratio < 1 or being in the highest quintile of CD8+ senescent (28CD-/CD57+) T cells] individuals equally divided amongst the cohorts. Multivariable linear regression revealed a distinct IRP+ group. Age and dialysis status did not predict immune senescence in kidney transplant candidates. NK cell features alone could discriminate IRP- and IRP+ patients, suggesting that NK cells significantly contribute to the overall immune status in kidney transplant candidates and that a combined T and NK cell phenotyping can provide a more detailed IRP definition. ImmuKnow® value was negatively correlated to age and significantly lower in IRP+ patients and predicts IRP when used alone or in combination with NK cell features. Conclusion: NK cells contribute to overall immune senescence in kidney transplant candidates.
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Células Asesinas Naturales/inmunología , Anciano , Relación CD4-CD8/métodos , Linfocitos T CD4-Positivos/inmunología , Antígenos CD57/inmunología , Linfocitos T CD8-positivos/inmunología , Estudios de Cohortes , Estudios Transversales , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/inmunología , Femenino , Citometría de Flujo/métodos , Humanos , Trasplante de Riñón/métodos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: Patients with anti-aminoacyl-tRNA synthetase (ARS) antibodies frequently experience complications of interstitial pneumonia (ARS-IP), and the computed tomography (CT) of ARS-IP frequently shows nonspecific interstitial pneumonia (NSIP) pattern. The CT pattern of ARS-IP might be different from that of idiopathic IP. However, the clinical differences in patients with ARS-IP and idiopathic IP showing the similar CT patterns have not yet been well studied. The objective of this study was to evaluate the clinical differences between patients with ARS-NSIP and idiopathic NSIP (I-NSIP). METHODS: Two groups of 34 patients each, with ARS-NSIP and I-NSIP, who visited Hiroshima University Hospital between January 2005 and December 2017, were enrolled. Clinical features and outcomes were retrospectively compared between the two groups. RESULTS: The ARS-NSIP group included more female patients and significantly younger patients than the I-NSIP group. The percentage of lymphocytes in bronchoalveolar lavage fluid (BALF) was significantly higher, and the CD4/CD8 ratio in BALF was significantly lower in the ARS-NSIP group compared with the I-NSIP group. The proportion of patients with traction bronchiectasis detected by CT was significantly higher in I-NSIP compared with ARS-NSIP. The number of patients who received corticosteroid and/or immunosuppressant therapy was significantly larger in the ARS-NSIP group than in the I-NSIP group. In addition, the patients in the I-NSIP group who underwent the immunosuppressive therapy demonstrated shorter survival than those who underwent no treatment; this tendency was not observed in the ARS-NSIP group. The 10-year survival rate of patients in the ARS-NSIP group was significantly higher than that of patients in the I-NSIP group (91.8% vs. 43.0%; log-rank, pâ¯=â¯0.012). The multivariate survival analysis revealed that positive anti-ARS antibody was an independent favorable prognostic factor in the patients with NSIP (OR, [95% CI]:0.12 [0.02-0.55], pâ¯=â¯0.013). CONCLUSIONS: Patients with ARS-NSIP had a significantly better prognosis than those with I-NSIP; this may be associated with the sensitivity to immunosuppressive therapies, and the different findings of BALF and HRCT between the two groups.
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Aminoacil-ARNt Sintetasas/antagonistas & inhibidores , Líquido del Lavado Bronquioalveolar/inmunología , Neumonías Intersticiales Idiopáticas/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Aminoacil-ARNt Sintetasas/inmunología , Autoanticuerpos/inmunología , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/epidemiología , Relación CD4-CD8/métodos , Femenino , Humanos , Neumonías Intersticiales Idiopáticas/diagnóstico por imagen , Neumonías Intersticiales Idiopáticas/tratamiento farmacológico , Neumonías Intersticiales Idiopáticas/fisiopatología , Inmunosupresores/uso terapéutico , Japón/epidemiología , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/fisiopatología , Linfocitos/citología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Tasa de Supervivencia , Tomografía Computarizada por Rayos X/métodosRESUMEN
Background : Several studies have provided evidence of CD4+ and CD8+ lymphocyte infiltration in various malignancies with probable implications for prognosis. Cervical cancer accounts for a major part of the cancer burden in the developing world. Study of genetically and ethnically diverse Indian cervical cancer patients is necessary to assess effects on lymphocytic infiltration of tumour tissue. Methods : This observational study was conducted over a period of 12 months with selected cervical cancer patients meeting inclusion criteria. Samples of cervical cancer tissue and peripheral blood were obtained and tumour infiltration with CD4+ and CD8+ lymphocytes was noted. Cell numbers were quantified by flow-cytometry and proportions compared between tumour and peripheral blood samples. Results: Tumour infiltration was noted with both CD4+ (13.93±10.95) and CD8+ (19.5±12.05) lymphocyte subtypes. However, compared to peripheral blood, CD4+ cells were significantly less predominant in tumour tissue (p, 0.0013). There was a statistically significant (p, 0.0004) reversal of the ratio of CD4+ and CD8+ in the tumour tissue (0.68±0.39) compared to peripheral blood (1.5±0.66) with maximal alteration in higher stage disease. Conclusion : The study revealed that T lymphocyte infiltration of cervical cancer tissue occurs but the ratio of CD4+ to CD8+ subtypes is sifnificantly lower than in peripheral blood, especially with in advanced stages of disease. The clinical implications of such a reversal of CD4+ and CD8+ ratios is unknown, but might have prognostic significance.
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Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Linfocitos Infiltrantes de Tumor/patología , Neoplasias del Cuello Uterino/patología , Adulto , Relación CD4-CD8/métodos , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Neoplasias del Cuello Uterino/inmunologíaRESUMEN
OBJECTIVE: In an attempt to understand better the potential role of the T cell in the pathogenesis of pulmonary fibrosis (PF) due to sulfur mustard gas inhalation, this study was designed to analyze bronchoalveolar lavage (BAL) lymphocyte subsets and to determine the ratio of CD4 to CD8 lymphocytes in BAL fluid. SETTING: University hospital. PATIENTS: Twenty-one veterans with mustard gas-induced pulmonary fibrosis and 20 normal veterans as control group. INTERVENTION: Chest roentgenograms, pulmonary function tests (PFTs), tests for carbon monoxide diffusing capacity of the lung (DLCO), high-resolution CT scans of the chest, BAL via fiberoptic bronchoscopy, analyses of BAL fluids for cellular and Flow-cytometric analysis of the phenotype of bronchoalveolar cells were performed in all cases. A transbronchial lung biopsy was done in all patients following BAL. RESULTS: Neutrophilic alveolitis was the predominant feature. Neutrophils (P<0.0001) and eosinophils (P=0.0006) were the predominant cell types in the BAL fluid of patients with PF. CD8 lymphocytes expressed as percentage or absolute number were significantly higher in patients with PF than in healthy controls (22.96+/-7.48% vs. 14.16+/-7.73%, respectively; P=0.0006; and 2.28+/-0.84 vs. 1.10+/-0.55 x 10(3) cells/ml, respectively; P<0.0001). The CD4/CD8 ratio was significantly lower in patients with PF than in healthy controls (0.73+/-0.25 vs. 1.58+/-0.67; P<0.0001). Except for the percentage and the absolute number of the BAL fluid neutrophils (r=0.70, P=0.001: r=-0.62, P=0.005; respectively), no correlation was found between DLCO% and the other BAL cells. A significant negative correlation was observed between the percentage of DLCO and both the percentage and the absolute number of CD8 lymphocytes in BAL fluid in patients with PF (r=-0.81, P=0.0003; r=-0.61, P=0.006; respectively). A significant correlation was also seen between the percentage of DLCO and the CD4/CD8 ratio (r=-0.60, P=0.006) in our patients. CONCLUSION: CD8 T cells in BAL fluid were significantly elevated in patients with pulmonary fibrosis. Patients with higher grades of pulmonary fibrosis expressed as percentage of DLCO, revealed higher percentages and the absolute number of CD8 T cells and a lower CD4/CD8 ratio.
Asunto(s)
Líquido del Lavado Bronquioalveolar/inmunología , Linfocitos T CD8-positivos/inmunología , Sustancias para la Guerra Química/efectos adversos , Gas Mostaza/efectos adversos , Fibrosis Pulmonar/inducido químicamente , Adulto , Líquido del Lavado Bronquioalveolar/citología , Relación CD4-CD8/métodos , Linfocitos T CD4-Positivos/inmunología , Monóxido de Carbono/fisiología , Humanos , Exposición por Inhalación/efectos adversos , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Recuento de Linfocitos/métodos , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/fisiopatología , Tomografía Computarizada por Rayos X/métodosRESUMEN
We have developed a lymphoproliferative disorder screening tube (LPD-ST) with the aim to provide comprehensive immunophenotyping of lymphocyte subsets with minimal need for additional testing. The LPD-ST consists of CD4/kappa FITC, CD8/lambda PE, CD3/CD14ECD, CD38PC5.5, CD20/CD56PC7, CD10APC, CD19APC-A700, CD5APC-A750, CD57/CD23PB and CD45KO. The LPD-ST was validated against previously used lymphocyte subset panels in Canada (n=60) and in Sweden (n=43) and against the OneFlow™ LST (n=60). The LPD-ST panel was then implemented in clinical practice using dried monoclonal antibody reagents (Duraclone® ) on 649 patient samples in Sweden. In 204 of 649 samples (31%), a monotypic B-cell population was found. Of these cases, a final diagnosis could be rendered in 106 cases (52%), and in the remainder, additional B-cell immunophenotyping was performed. In 20 (3%) samples, an aberrant T-cell population was confirmed by additional testing. Of 425 samples diagnosed as normal/reactive lymphoid tissue, 50 (12%) required additional immunophenotyping, mostly due to an abnormal CD4/CD8 ratio. The LPD-ST tube significantly minimizes the need for additional testing, improves the turn-around time, and reduces the cost of LPD immunophenotyping. It is also suitable for investigating paucicellular samples such as cerebrospinal fluid or fine needle aspirates.
Asunto(s)
Anticuerpos/química , Antígenos CD/sangre , Subgrupos de Linfocitos B/metabolismo , Citometría de Flujo/métodos , Inmunofenotipificación/métodos , Trastornos Linfoproliferativos/sangre , Subgrupos de Linfocitos T/metabolismo , Relación CD4-CD8/métodos , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: The close correlation between intracerebral pressure (ICP) and immunologic responses has been well described, but the role of T lymphocytes in this process remains unknown. This study targeted the relationship of circulating T lymphocytes and ICP in patients with intracerebral hemorrhage (ICH). METHODS: Between October 2015 and October 2016, consecutive patients age 18-65 years with ICH were enrolled. ICP values were recorded hourly for 5 days, and the screened patients were divided into 2 groups based on ICP: the elevated ICP group (ICP >20 mmHg) and normal ICP group (ICP ≤20 mmHg). Peripheral blood was collected on admission and T lymphocyte subpopulations were analyzed by flow cytometry. Glasgow Coma Scale score on admission and Glasgow Outcome Scale (GOS) score at 30 days after ICH were analyzed. RESULTS: A total of 44 patients were enrolled, including 18 patients in the elevated ICP group and 26 in the normal ICP group. Both CD3+ and CD4+ T lymphocyte counts were higher in the elevated ICP group (P = 0.004 and 0.000, respectively). The CD8+ T lymphocyte count was not significantly different between the 2 groups (P = 0.751). There were correlation trends between the maximum ICP value and CD3+ lymphocyte count (P = 0.003), CD4+ T lymphocyte count (P = 0.000), and the CD4+/CD8+ T lymphocyte ratio (P = 0.000). The area under the curve (AUC) of CD4+/CD8+ T lymphocyte ratio was the largest among them (P = 0.011 and 0.033), with a significant cutoff value and good specificity and sensitivity. There was a close correlation between the CD4+/CD8+ T lymphocyte ratio and the 30-day GOS score (P = 0.003, AUC = 0.812). CONCLUSIONS: The CD4+/CD8+ T lymphocyte ratio may be a valuable indicator for predicting postoperative ICP and the short-term prognosis after ICH.
Asunto(s)
Relación CD4-CD8/métodos , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Hemorragia Cerebral/sangre , Hipertensión Intracraneal/sangre , Adulto , Recuento de Células/métodos , Hemorragia Cerebral/cirugía , Femenino , Escala de Coma de Glasgow , Humanos , Hipertensión Intracraneal/cirugía , Presión Intracraneal/fisiología , Masculino , Persona de Mediana Edad , Linfocitos T/metabolismoRESUMEN
This study investigated the effect of n-3 fatty acid (FA)-containing parenteral nutrition on the circulatory lymphocyte subpopulation, intracellular cytokine and leukocyte adhesion molecule expression, and phagocytic activity in rats undergoing total gastrectomy. Normal rats with internal jugular catheters were assigned to normal control (NC) and two experimental groups and received total parenteral nutrition (TPN). At the same time, a total gastrectomy was performed in the experimental groups, whereas the NC group underwent a sham operation. The TPN solutions were isonitrogenous and identical in nutrient compositions except for differences in fat emulsion contents. The NC and one of the experimental groups received a soybean oil emulsion (SO), and the other experimental group received 50% soybean oil and 50% fish oil emulsion (FO). Half of the rats in each respective group were sacrificed 1 or 3 days after surgery or the sham operation to examine their immune response. The results showed that the FO group had a higher CD4 proportion and CD4/CD8 ratio than those of the SO and NC groups postoperatively. The phagocytic activity of peritoneal macrophages was higher in the FO group than in the NC group, but no difference was found between the SO and NC groups 3 days after surgery. The intracellular interferon (IFN)-gamma distribution in the FO group was higher than that of the SO group on postoperative days. Leukocyte adhesion molecule expressions and peritoneal monocyte chemotactic protein-1 levels were lower in the FO group than in the SO group on postoperative day 3. These results suggest that parenterally infused FO did not result in immunosuppression. In addition, FO administration promotes lymphocyte Th1 cytokine production, enhances peritoneal macrophage phagocytic activity, and reduces leukocyte adhesion molecule expression in rats with total gastrectomy.
Asunto(s)
Emulsiones Grasas Intravenosas/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Aceites de Pescado/administración & dosificación , Gastrectomía , Leucocitos Mononucleares/inmunología , Aceite de Soja/administración & dosificación , Animales , Relación CD4-CD8/métodos , Moléculas de Adhesión Celular/inmunología , Citocinas/sangre , Citocinas/inmunología , Ácidos Grasos Omega-3/inmunología , Aceites de Pescado/inmunología , Gastrectomía/efectos adversos , Inflamación/sangre , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Infusiones Parenterales/métodos , Masculino , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , Ratas , Ratas Wistar , Aceite de Soja/inmunologíaRESUMEN
BACKGROUND: Determining T-cell phenotypes of lung cells obtained by bronchoalveolar lavage (BAL) is frequently clinically useful, particularly for evaluating causes of interstitial lung disease. The current standard of determining CD4/CD8 T-cell subsets by immunohistochemical (IHC) staining of cytocentrifuge slides is labor-intensive and subject to interpreter variation. Flow cytometry (FCM) is a precise and rapid method commonly used in research to characterize cells in the lung. However, few studies address the methodology of analysis of BAL lymphocytes by FCM. METHODS: Patients underwent bronchoscopy for clinical purposes. A BAL cell differential and T-cell subtype was requested by the treating physician to supplement the evaluation of patients with suspected interstitial lung disease. We used a commercially available T-cell antibody reagent, approved for analysis of blood via FCM, for T-cell subtyping of clinical BAL specimens. RESULTS: The percentages of CD4 and CD8 T-cell populations, as well as the CD4/CD8 ratios showed excellent correlation with IHC staining of cytocentrifuge slides regardless of the acquisition program used, as long as the gating strategy remained consistent (r > or = 0.9693 for CD4, r > or = 0.9589 for CD8, and r > or = 0.9485 for the CD4/CD8 ratio). CONCLUSION: These findings validate the use of standardized, commercially available antibody cocktails for BAL lymphocyte subtyping, making this technique available to clinicians and researchers with access to a three-color or four-color flow cytometer.
Asunto(s)
Anticuerpos/inmunología , Líquido del Lavado Bronquioalveolar/citología , Citometría de Flujo/métodos , Inmunofenotipificación/métodos , Subgrupos de Linfocitos T/citología , Complejo CD3/análisis , Relación CD4-CD8/métodos , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Humanos , Inmunohistoquímica , Antígenos Comunes de Leucocito/análisis , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/patología , Recuento de Linfocitos , Reproducibilidad de los Resultados , Sarcoidosis Pulmonar/inmunología , Sarcoidosis Pulmonar/patología , Programas Informáticos , Coloración y Etiquetado/métodos , Subgrupos de Linfocitos T/inmunologíaRESUMEN
The enumeration of lymphocyte subsets plays an essential role in the monitoring of immunological disorders. Immunophenotyping values have been found to be influenced by race, age, gender, and environmental conditions. Therefore, it is important to establish reference ranges for healthy adults from the local population for clinical decision-making. The current study aimed to establish a normal reference range for peripheral blood lymphocyte subsets in healthy adults from the Chongqing District of China by using single-platform flow cytometry. Age- and gender-specific reference ranges were established in 268 healthy adult males and females between 21 and 60 years of age. The CD8+ cell counts decreased with age, CD4+ cell percentages and counts increased with age, and total T cell percentages were higher in the female population. Our results are similar to those reported from other parts of China but different from some results reported from other countries; this further stresses the need to establish local reference ranges by region. Our results will help in the management of patients with human immunodeficiency virus and other immunological disorders in Chongqing District. © 2015 International Clinical Cytometry Society.