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.

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.

Value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting radiation pneumonitis in patients with esophageal cancer and lung cancer / 国际肿瘤学杂志

Objective:To investigate the value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting the occurrence of radiation pneumonitis (RP) in patients with esophageal cancer and lung cancer.Methods:The clinicopathological data of 28 patients with esophageal and 16 patients with lung cancer undergoing radiotherapy from April 2018 to March 2020 in Hefei Cancer Hospital, Chinese Academy of Sciences were retrospectively analyzed, and the patients were divided into RP group ( n=16) and non-RP group ( n=28) according to whether RP occurred during and after treatment. The CD4/CD8 ratio and total B lymphocytes before radiotherapy between the two groups, and the CD4/CD8 ratio and total B lymphocytes before and after radiotherapy in the RP group were compared. Receiver operating characteristic curve was used to analyze the value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting RP. Results:The CD4/CD8 ratio before radiotherapy in the RP group was significantly lower than that in the non-RP group (0.993±0.179 vs. 1.708±0.170), with a statistically significant difference ( t=2.706, P=0.009); the total B lymphocytes in the RP group was significantly lower than that in non-RP group [(4.409±0.823)% vs. (8.153±1.017)%], with a statistically significant difference ( t=0.986, P=0.015). The CD4/CD8 ratio in the RP group was lower than that before radiotherapy when RP occurred (0.785±0.167 vs. 0.993±0.179), with no statistically significant difference ( t=1.376, P=0.189). The total B lymphocytes in the RP group was lower than that before radiotherapy when RP occurred [(3.487±1.018)% vs. (4.409±0.823)%], with no statistically significant difference ( t=0.804, P=0.433). The critical values of CD4/CD8 ratio and total B lymphocytes predicted RP were 0.580 and 0.357, respectively. The areas under the curve (AUC) of CD4/CD8 for predicting RP was 0.802 (95% CI: 0.653-0.932), the sensitivity was 89.29%, and the specificity was 68.75%. The AUC of total B lymphocytes for predicting RP was 0.694 (95% CI: 0.483-0.814), the sensitivity was 85.71%, and the specificity was 50.00%. The AUC of the two combined diagnostic method for RP was 0.834 (95% CI: 0.697-0.932), the sensitivity and specificity were 81.25% and 89.29%. AUC of the two combined tests was significantly higher than that of the single test, with statistically significant differences ( Z=1.115, P=0.046; Z=1.992, P=0.026). Conclusion:The CD4/CD8 ratio and total B lymphocytes in the RP group are lower than those in the non-RP group. The CD4/CD8 ratio and total B lymphocytes in the serum are of great significance in predicting the occurrence of RP in patients with malignant tumors receiving chest radiotherapy.

Características sociodemográficas y clínicas, según el índice CD4: CD8, de una población de personas infectadas con el VIH que consultó en la Corporación para Investigaciones Biológicas de Medellín, Colombia / Sociodemographic and clinical characteristics based on their cd4: cd8 ratio. of HIV infected persons who consulted at Corporación para Investigaciones Biológicas of Medellín, Colombia

RESUMEN Objetivo: las personas infectadas con el virus de la inmunodeficiencia humana tipo 1 (VIH-1+) con un índice CD4:CD8 menor a 1, presentan un mayor riesgo de morbilidad y mor-talidad por eventos no asociados con el SIDA. El objetivo de este trabajo fue explorar‚ en la población seleccionada‚ variables sociodemográficas y clínicas de acuerdo con dicho índice, debido a que este es más informativo que LT CD4+ y LT CD8+ por sí solos. Materiales y métodos: estudio observacional en pacientes con VIH-1+ atendidos en la Corporación para Investigaciones Biológicas (CIB). En 227 pacientes se evaluaron diferencias en edad‚ recuento de LT CD4+‚ carga viral‚ número y tipo de esquemas. Se dividieron los pacientes en dos grupos: (A con índice CD4:CD8 ≥ 1 y, B < 1). Resultados: el estudio se compuso de la siguiente forma, 71 % hombres y 29 % mujeres. El 22,5 % pertenecía al grupo A y el 77,5 % al B. La media de la edad fue 42‚8 años en el grupo A y 45 en el B (p = 0‚176). El 100 % de los individuos en el grupo A recibían tratamiento y, 97‚7 % en el B. La media de LT CD4+ fue de 772‚4 para el grupo A y, 448‚1 en el B (p = 0‚00001). En el grupo A el 90‚2 % tenían carga viral indetectable‚ en contraste con el 68‚8 % del B (p = 0‚002). El 41‚2 % en el grupo A tuvieron un solo esquema‚ en relación con el 43,8 % del B (p = 0‚744). Conclusiones: la mayoría de los pacientes presentaron un índice CD4:CD8 < 1 a pesar de haber presentado LT CD4+ aceptables. Fue más frecuente encontrar un índice < 1 en los pacientes sin un adecuado control virológico. Se requieren más estudios para determinar las variables asociadas con su normalización.

SUMMARY Introduction: Human Immunodeficiency Virus type 1 (HIV-1+) patients with a CD4:CD8 ratio < 1 presents a higher risk of morbidity and mortality due to not-associated AIDS events. The aim was to explore, in the selected population, sociodemographic and clinical variables, based on that ratio, because it is more informative than LT CD4+ and LT CD8+ by themselves. Materials and Methods: Observational, in HIV-1 infected patients attended at Biological Research Corporation. In 227 patients, age differences, LT CD4+ count, viral load, number and type of treatments were evaluated. The patients were divided in group A with a CD4:CD8 ratio equal or above to 1, and B bellow 1. Results: The study includes 71% of male and 29% of female. 22,5% were from group A and 77,5% from B. The mean of age was 42,8 years old in A and 45,3 years old in B (p=0,176). 100% of individuals from group A receive treatment, meanwhile 97,7% in B. Mean of LT CD4+ count was 772,4 cell/μL in A and 448,1 cell/μL in B (p=0,00001). In A, 90,2% had undetectable viral load vs 68,8% in B (p=0,002). 41,2% in A had only one type of treatment, vs 43,8% in B (p=0,744). Conclusion: Most of the patients had a CD4:CD8 ratio bellow to 1, despite an acceptable count of LTCD4++. To find a ratio bellow 1 in patients without an adequate virological control was more frequent. More studies to determinate variables associated with its normalization are required.

Preoperative peripheral blood CD4/CD8 ratio in predicting the prognosis of patients with coronary atherosclerotic heart disease after off-pump coronary artery / 中国胸心血管外科临床杂志

@#Objective    To investigate the role of preoperative peripheral blood CD4/CD8 ratio in predicting the prognosis of patients with coronary atherosclerotic heart disease (CAD) after off-pump coronary artery bypass grafting (OPCABG). Methods    A total of 118 patients with CAD who underwent OPCABG in our hospital from September 2016 to April 2017 were included in the study, including 82 males and 36 females aged 62.74±4.50 years. The primary end point was the incidence of major adverse cardiovascular events (MACE). Patients were divided into a high CD4/CD8 group (≥1.40, 62 patients) and a low CD4/CD8 group (<1.40, 56 patients) according to the results of flow cytometry. The correlation between CD4/CD8 ratio and prognosis of patients after OPCABG and the value of CD4/CD8 ratio for predicting postoperative MACE were evaluated. Results    Median duration of follow-up was 23.25 (20.91, 24.70) months, during which 21 patients (17.80%) experienced MACE and 4 patients (3.39%) were lost to follow-up. Kaplan-Meier analysis revealed that high CD4/CD8 group had a significantly higher MACE rate than the low CD4/CD8 group did (log-rank χ2=5.797, P=0.02). The results of adjusted Cox proportional hazards model showed that CD4/CD8 ratio (HR=3.103, 95%CI 1.557-6.187, P<0.01) was an independent risk factor of MACE in patients with CAD after OPCABG. The receiver operating characteristic curve showed that area under curve was 0.778 (95%CI 0.661-0.894, P<0.01), the optimal cut off value was 2.24, the sensitivity was 57.1%, and the specificity was 87.6%. Conclusion    Preoperative peripheral blood CD4/CD8 ratio is an independent predictor of MACE after OPCABG in patients with CAD.

Factores inmunológicos relacionados con VIH-1 en pacientes colombianos / Immunological Factors Related to HIV-1 in Colombian Patients / Fatores imunológicos relacionados com HIV-1 em pacientes colombianos

Resumen Introducción : los inflamasomas dirigen la maduración de las citoquinas IL-1b e IL-18, las cuales contribuyen en la patogénesis de la infección por VIH-1. Dada la complejidad de la infección, se hace necesaria la búsqueda de marcadores que permitan identificar nuevos blancos terapéuticos o hacer seguimiento del estado inmunológico de los pacientes. Por lo tanto, el objetivo del presente trabajo fue explorar el efecto independiente de los principales componentes inflamatorios sobre la infección por VIH-1. Materiales y métodos : estudio analítico con 36 pacientes VIH+ y 36 controles sanos, pareados por edad y sexo. Se cuantificó la carga viral, los linfocitos T CD4+/CD8+, el perfil lipídico, la proteína C reactiva y las concentraciones séricas de IL-1-ß, IL-6 e IL-18. El HIRNA de los genes relacionados con los inflamasomas fue cuantificado por RT-PCR en tiempo real. El análisis estadístico se basó en medidas de resumen, pruebas de hipótesis y regresión logística binaria multivariante. Resultados : se encontraron menores valores de HDL y HIRNA IL-18 y mayores de HIRNA NLRPI y HIRNA ASC en los pacientes con VIH-1, comparados con los controles. Los valores de HDL y HIRNA IL-18 se correlacionaron con los recuentos de linfocitos. En el análisis multivariado se encontró que la relación CD4/CD8, el mRNA IL-18 y el HIRNA ASC pueden constituir las principales variables que tienen un potencial explicativo sobre la infección por VIH-1 en la población de estudio. Conclusión : se evidenció la importancia de estudiar los inflamasomas, dado que en la población de estudio constituyen potenciales blancos terapéuticos para disminuir la respuesta inflamatoria.

Abstract Introduction : Inflammasomes direct the maturation of the cytokines IL-1ß and IL-18, which contribute to the pathogenesis of HIV-1 infection. Given its complexity, it is necessary to search for markers that can identify new therapeutic targets or monitor the immunological status of patients. Therefore, the objective of the present work was to explore the independent effect of the main inflammatory components on HIV-1 infection. Materials and Methods : Researchers conducted an analytical study with 36 HIV+ patients and 36 healthy controls, matched by age and sex. Viral load, CD4+/CD8+ T lymphocytes, lipid profile, C-reactive protein and serum concentrations of IL-1ß, IL-6, and IL-18 were quantified. RT-PCR in real time quantified the ITIRNA of the genes related to the inflammasomes. The statistical analysis based on summary measures, hypothesis tests, and multivariate binary logistic regression. Results : Lower values of HDL and ITIRNA IL-18 and higher ITIRNA NLRPI and ITVRNA ASC presented in patients with HIV-1 compared with controls. The values of HDL and ITIRNA IL-18 correlated with lymphocyte counts. The multivariate analysis shows that the CD4 / CD8 ratio, the IL-18 ITIRNA and the ASC ITIRNA can be the main variables that have an explanatory potential on HIV-1 infection in the study population. Conclusion : The importance of studying inflammasomes was evidenced, given that in the study population they are potential therapeutic targets to reduce the inflammatory response.

Resumo Introdução : os inflamassomas dirigem a maduração das citocinas IL-1ß e IL-18; as quais contribuem nas patogêneses da infeção por HIV-1. Dada a complexidade da infeção se faz necessária a busca de marcadores que permitam identificar novos alvos terapêuticos ou fazer seguimento do estado imunológico dos pacientes. Portanto, o objetivo do presente trabalho foi explorar o efeito independente os principais componentes inflamatórios sobre a infeção por HIV-1. Materiais e métodos : estudo analítico com 36 pacientes HIV+ e 36 controles saudáveis, pareados por idade e sexo. Se quantificou a carga viral, os linfócitos T CD4+/CD8+, o perfil lipídico, a proteína C reativa e as concentrações séricas de IL-1ß, IL-6 e IL-18. O ITIRNA dos genes relacionados com os inflamassomas foi quantificado por RT-PCR em tempo real. A análise estatística se baseou em medidas de resumo, provas de hipótese e regressão logística binaria multivariado. Resultados : se encontraram menores valores de HDL e TÍTRNA IL-18 e maiores de TÍIRNA NLRPI e TÍTRNA ASC nos pacientes com HIV-1, comparados com os controles. Os valores de HDL e TÍTRNA IL-18 se correlacionaram com os recontos de linfócitos. Na análise multivariada encontrou-se que a relação CD4/CD8, o TÍIRNA IL-18 e o TÍTRNA ASC podem constituir as principais variáveis que têm um potencial explicativo sobre a infeção por HIV-1 na população de estudo. Conclusão : se evidenciou a importância de estudar os inflamassomas, dado que na população de estudo constituem potenciais brancos terapêuticos para diminuir a resposta inflamatória.

Correlation between plasma 25-hydroxyvitamin D levels and the CD4+/CD8+ ratio in elderly men in different states of glucose metabolism / 中华老年医学杂志

Objective To investigate the correlation between plasma 25-hydroxyvitamin D(25-OHVD)levels and the CD4+/CD8+ ratio in elderly men in different states of glucose metabolism.Methods Clinical data of 206 elderly male patients at the geriatrics department of our hospital from April 2011 to August 2017 were collected and retrospectively analyzed.There were 85 patients with type 2 diabetes mellitus(T2DM),39 patients with impaired glucose tolerance(IGT) and 82 patients with normal glucose tolerance(NGT).Locally weighted regression and multivariate generalized linear regression models were used to analyze the correlation between plasma 25-OHVD levels and the CD4+/CD8+ ratio.Results There were significant differences in two-hour postprandial blood glucose and homeostasis model assessment of insulin resistance(HOMA-IR) between the NGT,IGT and T2DM groups (6.5 mmol/L,9.2 mmol/L vs.11.0 mmol/L,11.92 ± 10.57,16.46 ± 10.89 vs.32.67±7.39,respectively,P ＜0.01).Fasting plasma glucose and 2-hour postprandial insulin levels were higher in the IGT and T2DM groups than in the NGT group(5.1 mmol/L,6.3 mmol/L vs.4.9 mmol/L,440.5 nmol/L,367.8 nmol/L vs.255.4 nmol/L,P＜0.05).The haemoglobin A1c(HbA1c)level was higher in the T2DM group than in the NGT and IGT groups(7.1％ vs.5.5％ and 5.8％,P＜0.05).The 25-OHVD and CD4+ levels in the T2DM group were lower than those in the NGT and IGTgroups[11.6 μg/L vs.18.3 μg/L and 17.4 μg/L,(34.0±11.8)％ vs.(40.7±10.5)％ and (40.7±10.2)％,P＜0.01],but were not significantly different between the NGT and IGT groups(P ＞0.05).The CD4+/CD8+ ratios in the T2DM and IGT groups were not significantly different from each other(1.4 vs.1.6,P＞0.05),but were lower than that in the NGT group(2.7,P＜0.01).After adjusting for the influence of related confounders,CD4+/CD8+ increased by 0.4 on average with each standard deviation(7.62 μg/L)increase of 25-OHVD.Compared with 25-OHVD patients in the first quartile,CD4+/CD8+ in the second,third and fourth quartile increased by 0.7,0.9 and 1.1 respectively on average,showing a significant positive correlation and a significant linear trend in the level of 25-OHVD and the CD4+/CD8+ ratio(P＜0.01).Conclusions With the aggravation of glucose tolerance,plasma 25-OHVD levels and the CD4+/CD8+ ratio decrease by varying degrees in elderly men.The deficiency of plasma 25-OHVD may be an independent risk factor for a low CD4+ /CD8+ ratio.

Influence of comorbidities on CD4+/CD8+ proportion in HIV-positive patients in Blumenau, State of Santa Catarina: a retrospective study

Abstract INTRODUCTION: The objective was to identify comorbidities related to HIV-positive patients in Blumenau, State of Santa Catarina. METHODS: A retrospective, descriptive observational design study which analyzed data from 424 patients assisted by the sexually transmitted disease/acquired immunodeficiency syndrome (STD/AIDS) Specialized Care Service (SCS). RESULTS: Of 424 medical records analyzed, 388 patients presented CD4+/CD8+ ratios lower than 1. The most prevalent comorbidities were smoking, depression, alcoholism, and herpes zoster infection, in males and females. CONCLUSIONS: The most relevant comorbidity in both genders was herpes zoster, an important marker of immunity in patients. The lowest mean was observed among patients with neurotoxoplasmosis.

Value of high sensitive c-reactive protein and CD4/CD8 ratio for monitoring of lung infection in elderly patients with esophageal cancer / 国际检验医学杂志

Objective To explore the value f high sensitive c-reactive protein (hs-CRP) and CD4/CD8 ratio for monitoring of lung infection in elderly patients with esophageal cancer through detecting hs-CRP ,white blood cell (WBC)parameters and CD4 /CD8 ratio .Methods A total of 89 lung infection elderly patients with esophageal cancer after surgery from August 2012 to Decem-ber 2014 were collected as observation group ,special protein instrument ,blood cell analyzer and flow cytometry instrument were used to detect the hs-CRP ,WBC parameters ,CD4/CD8 ratio ,and compared with 82 cases of retired veteran cadres physical exami-nation for the same period in the control group .Results The hs-CRP ,WBC parameters ,CD4/CD8 in the preoperative group and the control group had no significant difference (P> 0 .05) .The three indicators in the preoperative group ,infection group and 3 days group had significant differences (P < 0 .05) ,although CD4/CD8 ratio in the cure group improved ,had not been completely im-proved .Conclusion Hs-CRP in diagnosis and monitoring of therapeutic efficacy is better than WBC parameters ,in the treatment of lung infection in elderly patients with esophageal cancer ,besides use the anti-infection treatment ,promote immune function recovery should not be ignored .

Avaliação da migração de neutrófilos e da frequência relativa de linfócitos CD4+/CD8+ em crianças com síndrome de Down e controles / Evaluation of both neutrophil migration and the relative frequency of CD4+/CD8+ limphocytes in children with Down syndrome and controls

Objetivos: Avaliar a migração de neutrófilos e a frequência relativa de linfócitos CD4+/CD8+ em crianças com síndrome de Down e controles saudáveis.Métodos: Este foi um estudo de caso-controle realizado no Instituto de Pesquisas Biomédicas, no Hospital São Lucas da PUCRS. Os pacientes do grupo de estudo foram selecionados por uma amostragem de conveniência, representando todas as crianças com síndrome de Down e idade entre três e 13 anos, que frequentavam os ambulatórios de Pediatria e de Otorrinolaringologia do Hospital São Lucas da PUCRS e do Kinder - Centro de Integração da Criança Especial, em Porto Alegre, Rio Grande do Sul, nos meses de janeiro e dezembro de 2012. Para o grupo controle foram recrutadas crianças saudáveis e sem síndrome de Down, participantes de outro estudo em andamento no Instituto de Pesquisas Biomédicas. Foram selecionados os pacientes com maior volume de células armazenadas em criotubos. Para avaliar os parâmetros da resposta imune, foram realizados ensaio de quimiotaxia de neutrófilos e imunofenotipagem de células T CD4+ e CD8+. Associações foram avaliadas pelo teste do qui-quadrado, t de Student ou Mann-Whitney. Todos os testes foram bidirecionais e as diferenças foram consideradas significativas quando p menor que 0,05.Resultados: Foram incluídos 19 pacientes (13 com síndrome de Down e seis controles), com médias de idade de 8,13 e 9,83 anos, respectivamente. Não foram observadas alterações significativas no grupo com síndrome de Down em relação à capacidade de migração dos neutrófilos. Houve uma tendência a valores percentuais menores de células T CD4+ e maiores de CD8+ para o grupo com síndrome de Down. Houve diferença significativa na relação CD4+/CD8+ entre os dois grupos, sendo a mesma menor no grupo com síndrome de Down.Conclusões: Este estudo sugere que os pacientes com síndrome de Down apresentam uma taxa CD4+/CD8+ diminuída, o que pode contribuir para as infecções frequentes e recorrentes nessas crianças.

Aims: To evaluate neutrophil migration and the relative frequency of CD4+/CD8+ lymphocytes in children with Down syndrome and in healthy controls.Methods: This was a case-control study carried out at the Institute of Biomedical Research, affiliated with São Lucas Hospital of the Pontifical Catholic University of Rio Grande do Sul (PUCRS). Patients with Down syndrome were selected by convenience sampling, including all children with Down syndrome aged 3 to 13 years treated at the Pediatric and Otolaryngology Outpatient Clinics of São Lucas Hospital and at Kinder - Center for Children with Special Needs, in Porto Alegre, State of Rio Grande do Sul, Brazil, between January and December 2012. Healthy children without Down syndrome, participants in another ongoing study conducted by Institute of Biomedical Research, were recruited to the control group. Those patients with the largest volume of cells stored in cryotubes were selected. A neutrophil chemotaxis assay and immunophenotyping of CD4+ and CD8+ T cells were performed to evaluate the functionality of the immune response. Associations were assessed by the chi-squared test, Student's t test, or Mann-Whitney's test. All tests were bidirectional, and p values less than 0.05 were regarded as statistically significant.Results: This study included 19 patients (13 with Down syndrome and six controls), with a mean age of 8.13 and 9.83 years, respectively. No significant changes concerning neutrophil migration were observed in the Down syndrome group. However, patients with Down syndrome tended to have a lower rate of CD4+ T cells and a higher rate of CD8+ T cells. The CD4+/CD8+ ratio revealed significant difference between the groups, being lower in patients with Down syndrome.Conclusions: This study suggests that patients with Down syndrome show a decreased CD4+/CD8+ ratio, which may contribute to the frequent and recurrent infections in these children.

Investigation on T-lymphocyte subsets absolute counting and CD4+/CD8+ratio in healthy adults of Ugyur and Han nationalities in Karamy / 国际检验医学杂志

Objective To built the reference range of peripheral blood T-lymphocyte subsets including CD3+ ,CD4+ ,CD8+ and CD4+ /CD8+ ratio in healthy adults of Ugyur and Han nationalities and to provide basis for the diagnosis ,therapy and prognosis of disease .Methods A total of 181 blood samples were collected from healthy adults .The cell chip quantitative detection technology was used to detect CD3+ ,CD4+ and CD8+ ,CD3+ ,CD4+ absolute value ,CD8+ and CD4+ /CD8+ ratio were compared between Ugyur and Han nationalities .Results CD8+ absolute counting and CD4+ /CD8+ ratio had no significant difference between Ugyur and Han nationalities(P>0 .05) ,while the CD3+ ,CD4+ absolute counting had significant difference(P<0 .05) .Conclusion The discrepancy of territory and living environment should be taken into account for building a reference values of CD4+ .

Association between CD4+/CD8+ ratio in peripheral blood before hepatectomy for liver cancer and patient prognosis / 临床肝胆病杂志

ObjectiveTo investigate the association between CD4+/CD8+ ratio in peripheral blood and patient prognosis after hepatectomy for liver cancer. MethodsThe clinical data of 150 patients who received partial hepatectomy for liver cancer in the 180 Hospital of PLA from October 2008 to November 2011 were analyzed retrospectively. CD4+/CD8+ ratio in peripheral venous blood was measured before surgery, and the patients were divided into low-CD4+/CD8+ group (CD4+/CD8+ ratio ≤1, 52 patients) and high-CD4+/CD8+ group (CD4+/CD8+ ratio ＞1, 98 patients). Clinical indices were compared between the two groups, and outpatient follow-up and telephone follow-up were applied to record survival rate and tumor recurrence. The chi-square test was applied for comparison between the two groups, and Kaplan-Meier method (log-rank test) was applied for survival analysis. Univariate and multivariate logistic regression analyses were performed for clinical factors to determine the related risk factors for recurrence after hepatectomy for liver cancer. ResultsThe low-CD4+/CD8+ group had significantly lower 1-, 3-, and 5-year survival rates than the high-CD4+/CD8+ group (χ2=36.473, 41983, and 55.214, respectively; all P＜0.001), and the 5-year survival rate differed significantly between the two groups (χ2=81.471; P＜005); the low-CD4+/CD8+ group had significantly higher 1-, 3-, and 5-year tumor recurrence rates than the high-CD4+/CD8+ group (χ2=44.041, 68.234, and 55.157, respectively; all P＜0.05). Univariate analysis showed that CD4+/CD8+ ratio, tumor diameter, existence of satellite lesions, hepatitis B virus infection, depth of tumor invasion, microvascular invasion, lymph node metastasis, and degree of tumor differentiation were high risk factors for recurrence after resection of liver cancer. Multivariate analysis showed that CD4+/CD8+ ratio, tumor diameter, degree of tumor differentiation, lymph node metastasis, and microvascular invasion were independent risk factors for recurrence after resection of liver cancer. ConclusionThe patients with a CD4+/CD8+ ratio of ≤1 before resection of liver cancer have poor prognosis and high recurrence rates, and CD4+/CD8+ ratio has a certain predictive value for prognosis after resection of liver cancer.

Poikiloderma Vasculare Atrophicans Showing Features of Ashy Dermatosis in the Beginning

Poikiloderma vasculare atrophicans (PVA) is a rare poikilodermatous variant of early-stage mycosis fungoides characterized by generalized poikiloderma, atrophy, mottled dyspigmentation, and telangiectasia. In 2001, a 14-year-old male presented with asymptomatic brownish-gray polymorphic macules throughout the body with flexural accentuation. A skin biopsy showed increased melanophages with focal hydropic changes. Ashy dermatosis was considered a possible diagnosis. In 2005, the lesions began to show darkening and lichenification in the lower part of the trunk. In 2011, his skin showed definite poikilodermatous changes, and a biopsy showed band-like inflammatory infiltrations of atypical lymphocytes, epidermal atrophy, and epidermotropism of predominantly CD4-CD8+ atypical T cells. In addition, results of T-cell receptor gene rearrangement analysis were positive. Based on the aforementioned findings, he was diagnosed with PVA. If a patient shows long-standing and progressive hyperpigmentary skin changes, periodic follow-up and repeated skin biopsies are recommended to determine the underlying condition.

Perfil de risco imunológico de idosas com câncer de mama: os primeiros 37 casos / Immune risk profile of elderly women with breast cancer: the first 37 cases

Objetivos: Avaliar o perfil imunológico de risco em idosas com câncer de mama e testar se este pode ser um fator preditivo confiável para determinar tipos de tratamento e seguimento oncológico.Métodos: Foram pesquisadas a relação das células T CD4+/CD8+ e a sorologia para citomegalovírus no sangue periférico de mulheres com 60 anos ou mais de idade no momento do diagnóstico da neoplasia mamá¡ria, que realizaram tratamento cirúrgico no Centro de Mama da Pontifí­cia Universidade Católica do Rio Grande do Sul pelo Sistema Único de Saúde. Foram excluí­das da pesquisa pacientes com sorologia positiva para HIV, com imunossupressão após transplante de órgãos e as que realizaram quimioterapia neoadjuvante. Os dados foram comparados em grupos conforme o comprometimento axilar, o tamanho tumoral, o perfil imunohistoquí­mico do tumor e a ocorrência de eventos adversos (recidiva axilar, recidiva local do tumor e/ou metástases). Nos casos de eventos adversos, foi realizada uma nova contagem de CD4+ e CD8+.Resultados: Foram incluídas 37 pacientes, entre as quais 10 tiveram metástases axilares. As pacientes com axila positiva para metástases apresentaram uma relação CD4+/CD8+ maior que nos casos de axila negativa para metástases (p=0,04). Não foi encontrada diferença estatisticamente significativa em relação ao tamanho e perfil imunohistoquí­mico do tumor. No seguimento médio de 14,3 meses, ocorreram dois eventos adversos (uma recidiva axilar e um caso de metástases ósseas), quando se observou um aumento na relação das células T pesquisadas.Conclusões: A relação das células T CD4+/CD8+ parece aumentar nos casos de câncer de mama de pior prognóstico. Tanto quanto foi possível pesquisar na literatura, estes são os primeiros dados sobre células T CD4+ e CD8+ no sangue periférico de mulheres idosas com câncer de mama. Um seguimento maior poderá determinar o valor destas células como fator prognóstico e/ou preditivo.

Aims: To evaluate the immune risk profile of elderly women with breast cancer and to assess whether this can be a reliable predictor to determine types of treatment and oncologic follow-up.Methods: We assessed the CD4+/CD8+ ratio in peripheral blood cell, as well as serology for cytomegalovirus, of 37 women who were aged 60 years or more at the time they were diagnosed with breast cancer/. They all had surgical treatment at the Breast Center from Pontificia Universidade Catolica do Rio Grande do Sul. Those with positive serology for HIV, or immuno suppressed due to organ transplant, as well as those who had neoadjuvant chemotherapy. Data was analyzed according to axillary involvement, tumor size, tumor immunohistochemical profile and occurrence of adverse events (axillary relapse, local relapse and/or metastases).Results: The mean value of CD4+/CD8+ ratio was 1.72 (min. 1.1, max. 2.32) and cytomegalovirus serology was positive in all subjects. Comparing the groups, patients with positive axillary metastases (n=10) had a CD4+/CD8+ ratio greater than in those with negative axillary metastases (p=0.04). No statistically significant difference was detected regarding the size and immunohistochemical profile of the tumor. Two adverse events occurred at a mean follow-up of 14 months (one axillary relapse and one bone metastasis), when an increase in the CD4+/CD8+ ratio was observed.Conclusions: The CD4+/CD8+ ratio appear to increase in cases of breast cancer with worst prognosis. As far as was possible to search, these are the first data on CD4+ and CD8+ peripheral blood of elderly women with breast cancer. A longer follow-up will determine the value of these cells as a prognostic and/or predictive marker.

Preoperative blood CD4+/CD8+ ratio as an independent predictor of postoperative recurrence after hepatectomy for hepatocellular carcinoma / 中华肝胆外科杂志

Objective To study the predictive value of preoperative blood CD4 +/CD8 + ratio in postoperative recurrence after hepatectomy for patients with hepatocellular carcinoma.Methods The clinical data of 67 patients who underwent hepatectomy for hepatocellular carcinoma at The Fifth Hospital Affiliated to Sun Yat-sen University were analyzed retrospectively.Using the preoperative blood CD4 +/CD8 + ratio,these patients were divided into 2 groups,the CD4 +/CD8 + ＜ 1 group and the CD4 +/CD8 + ≥ 1 group.These patients were followed up at the outpatient clinic and/or by telephone till June 2013.The Cox ratio risk pattern analysis was used to determine the significant risk factors of tumor recurrence.Results On univariate analysis,preoperative AFP ≥400 μg/L,maximum diameter of tumor ＞ 5 cm,number of tumor ＞ 3,CD4 +/CD8 + ＜ 1,vascular invasion,positive resection margin,and portal vein tumor thrombus were risk factors of poor disease-free survival (P ＜ 0.05).On multivariant analysis,CD4 +/CD8 + ＜ 1,number of tumor ＞ 3,and portal vein tumor thrombus were independent predictors of poor disease-free survival after hepatectomy for hepatocellular carcinoma (P ＜ 0.05).Conclusions Preoperative CD4 +/CD8 + ＜ 1 was an independent adverse predictor of poor disease-free survival.It was valuable in predicting postoperative recurrence of hepatocellular carcinoma.

The variation of system immune and intestinal immune in non-alcoholic fatty liver disease in rats / 中华消化杂志

Objective To study the changes of system immune and intestinal immune in the progression of non-alcoholic fatty liver disease due to obesity. Methods Ninty male SD rats were divided into control, high-sucrose and high-fat diet groups. Non-alcoholic fatty liver disease models were established by feeding with high-sucrose diet or high-fat diet and were killed at the 4th,8th and 12th weeks with 10 each for each group. The extent of liver steatosis was observed with HE staining.Portal blood endotoxin level was assessed by limulus test. The percentage of CD4+ and CD8+ cells in peripheral blood mononuclear cells (PBMC) and lymphocytes in Peyer's patches (PP) were calculated by flowcytometry. Results In comparison with control group, the endotoxin level was not elevated from the 4th week to 12th week in high-sucrose diet group, (all P values＞0.05), but was increased in high-fat diet group at the 8th week (P＜0.05). CD4/CD8 ratio in PBMC was higher in high-sucrose and higt-fat diet groups than that in control group at the 4th week (P＜0. 05) ,but was lower than that in control group at the 8th and 12th weeks (P＜0. 05). Whereas the variation of CD4/CD8 ratio in PP was consisted with that in PBMC between the high-sucrose and high-fat diet groups at the 4 th and 8 th weeks, but there was no difference when compared with control group at the 12 th week (P＞0.05).Conclusion Obesity can inhibit systematic immune and intestinal immune. The intestinal immune may be regulated by the liver.

Influence of Fu Fang Xiao Chai Hu Tang on level of interleukin-2 and value of CD4~+/CD8~+ in mice bearing Ehrlish ascites carcinoma / 中国病理生理杂志

AIM:To investigate the effects of Fu Fang Xiao Chai Hu Tang(FFXCHT)on level of Interleukin-2 and value of CD4+/CD8+ in mice bearing Ehrlish ascites carcinoma(EAC).METHODS:The effects of FFXCHT on the EAC were observed and index of thymus and spleen were observed.The method of [3H]-TdR incorporation was used to measure the IL-2 level,and the value of CD4+/CD8+ was assayed by ELITE calibur flow cytometry.RESULTS:Compared with the model group,FFXCHT inhibited the growth of EAC(P

Influence of Direct Moxibustion with Moxa Cones the Size of a "Rice Grain" on Cell count and Proportion of Leukocytes in Rabbit and Human Peripheral Blood / 日本東洋医学雑誌

With the purpose of clarifying the influence of direct moxibustion on the cell count and proportion of leukocytes in peripheral blood, rabbits and humans were treated with direct moxibustion. The moxa cones were the size of a “rice grain”. In the rabbits 10 moxa cones were distributed among four points which were selected on the low back. Humans were treated with the same method except eight points were chosen on the back and legs. Peripheral blood was collected periodically following each treatment. Leukocyte counts and leukocyte differentials were then measured. Lymphocyte subpopulations were also analyzed with flow cytometry in humans.<br>In rabbits, the mean leukocyte count increased transiently after the treatment in both the moxibustion group and the control group. However, the greatest increase was observed in the moxibustion group. In humans, no change was found in leukocyte counts and leukocyte differentials in the moxibustion group. However, the mean T cell percentage in the moxibustion group decreased 24 hours after the moxibustion treatment. Moreover, the mean CD4/CD8 ratio of the moxibustion group increased 2 hours after the treatment, and decreased 24 hours after the treatment. These changes were statistically significant while no significant change was observed in the control group. No change was found in either rabbits or humans after the 4 weeks of treatment.<br>These results suggest that the immune system will be influenced by moxibustion at least transiently.

Lymphocyte Subpopulations in Patients with Minimal Change Disease and IgA Nephropathy / 대한신장학회잡지

The pathogenetic mechanisms of minimal change disease and immunoglobulin A nephropathy remain uncertain, but recently various reports have reported the important role of the immunological aspect in the pathogenesis of glomerular injury. To assess the abnormalities of immunoregulatory system in these glomerular disease, the percentages of lymphocyte subpopulations in peripheral blood were studied in 24 cases of minimal change disease and 28 of immunoglobulin A nephropathy diagnosed by renal biopsy. The results were as follows: 1) CD4/CD8 ratio of the minimal change disease was significantly increased, compared with normal controls and immunoglobulin A nephropathy(P<0.05). 2) No significant difference in T helper cell and T suppressor cell was found between steroid response group and steroid non-response group in minimal change disease. 3) No significant difference in lymphocyte subpopulation was found between group with nephrotic range of proteinuria and group without nephrotic range of proteinuria in minimal change disease. 4) The discrepancies in lymphocyte subpopulations was not observed between group with infection and group without infection in immunoglobulin A nephropathy. 5) The pathologic grade (criteria of WHO) did not demonstrate a significant difference in lymphocyte subpopulation in immunoglobulin A nephropathy. In conclusion, these results suggest that the dysregulation of cell-mediated immunologic system is involved in the pathogenesis of minimal change disease and immunoglobulin A nephropathy, and some differences of immunoregulatory abnormalities between minimal change disease and immunoglobulin A nephropathy exist. But in this study the change in lymphocyte subpopulation does not anticipate the clinical course and prognosis of minimal change disease and immunoglobulin A nephropathy.