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.

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.

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.

Significance of changes in CD4 -CD8 -double negative T lymphocytes in peripheral blood of children with Mycoplasma pneumoniae pneumonia / 中华实用儿科临床杂志

Objective:To discuss the changes and clinical significance of CD4 -CD8 -double negative T lymphocytes (DNT), T lymphocyte subsets, natural killer (NK) cells and CD 19+ B lymphocytes in peripheral blood of children with confirmed Mycoplasma pneumoniae pneumonia(MPP). Methods:A retrospective analysis was conducted on children with pneumonia admitted to the Children′s Hospital of Shanghai Jiaotong University from January 2019 to February 2020.The patients were stratified into 3 age groups: 0-3 years old, 4-7 years old and ≥8 years old, and they received detection of peripheral blood T lymphocyte subsets in acute stage.As observation group, 185 MPP children were further divided into MPP common group (117 cases) and MPP severe group (68 cases) based on their state of pneumonia.In addition, 69 cases with non-MPP were selected as control group.The absolute counts of DNT, T lymphocyte subsets, NK cells and CD 19+ B lymphocytes in peripheral blood were tested by flow cytometry.DNT levels in diffe-rent age groups were analyzed. Results:(1) The number of CD3 + [1.527(1.059, 2.348)×10 9/L], CD4 + [0.771(0.559, 1.206)×10 9/L], CD8 + [0.528(0.343, 0.773)×10 9/L], CD4 + /CD8 + [1.570(1.130, 1.945)], CD 19+ [0.455(0.285, 0.771)×10 9/L] and DNT[0.168(0.095, 0.294)×10 9/L] lymphocytes in peripheral blood in the observation group were lower than those in the control group[2.116(1.506, 3.728)×10 9/L, 1.170(0.685, 2.114)×10 9/L, 0.696(0.414, 1.226)×10 9/L, 1.780(1.230, 2.210), 0.694(0.483, 1.343)×10 9/L, 0.235(0.134, 0.391)×10 9/L], and the differences were statistically significant (all P<0.05). (2) In addition, the number of CD3 + [1.704(1.215, 2.566)×10 9/L], CD4 + [0.855(0.628, 1.267)×10 9/L], CD8 + [0.582(0.378, 0.843)×10 9/L], NK[0.269(0.176, 0.417)×10 9/L], CD 19+ [0.461(0.317, 0.808)×10 9/L] and DNT[0.180(0.117, 0.306)×10 9/L]lymphocytes in peripheral blood in MPP common group were significantly higher than those in MPP severe group [1.369(0.831, 1.760)×10 9/L, 0.676(0.433, 0.924)×10 9/L, 0.495(0.292, 0.699)×10 9/L, 0.196(0.112, 0.380)×10 9/L, 0.391(0.181, 0.730)×10 9/L, 0.143(0.071, 0.265)×10 9/L], and the differences were statistically significant (all P<0.05). (3) Moreover, in acute phase, the number of DNT in observation group had no significant differences with that in control group of the same age ( P>0.05). In the observation group, the number of DNT[0.230(0.125, 0.364)×10 9/L] in 0-3 years old group was higher than that in 4-7 years old group[0.143(0.085, 0.233)×10 9/L] and ≥ 8 years old group[0.144(0.078, 0.271)×10 9/L]. In 0-3 years old group, the more serious the disease, the lower the indicators, and the differences were statistically significant (all P<0.05). Conclusions:In acute phase, the changes of lymphocyte subsets in peripheral blood of MPP children are remarkable, and the absolute count of DNT lymphocytes in peripheral blood decreased.The decreasing level of DNT has negative association with the severity of pneumonia.The absolute count of DNT was higher in young children.So monitoring peripheral blood DNT may be of some value to the assessment of immune function or pneumonia state in children with MPP.

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.

Aquios CL flow cytometer performance in the automated quantification of lymphocyte subpopulations / Desempenho do citômetro de fluxo Aquios CL na quantificação automatizada de subpopulações linfocitárias

ABSTRACT Flow cytometry (FC) is an essential tool for diagnosis, prognosis and therapeutic follow-up of several hematologic malignancies. In addition, it performs the quantification of lymphocytes subpopulations for diagnosis and monitoring of primary and acquired immunodeficiencies through the antigenic expressions of CD19 and CD20 for B lymphocytes; CD2, CD3, CD4, CD8 for T lymphocytes; and CD56 and CD16 for the identification of natural killer (NK) cells. The cytometry technique has revolutionized the way that the cells are identified, and over the years this platform has progressed with several advances in hardware and software that aim to improve workflow resulting in higher productivity, quality and cost savings. The Aquios CL - Beckman Coulter (BC) is an example of this advance because it is a complete automation instrument in flow cytometry called "Load & Go flow cytometer" for quantification of lymphocyte subpopulations in the routine diagnosis. In this study, the Aquios CL was validated, and quantification in frequency and absolute numbers of the lymphocyte subpopulations had an excellent correlation with the results obtained by the dual platform quantification performed in the Cytomics FC500 (BC) and automated Sysmex XE-2100 cell analyzer.

RESUMEN La citometría de flujo (CF) es una herramienta importante para diagnóstico, pronóstico y seguimiento terapéutico de diversas neoplasias hematológicas. Además, posibilita la cuantificación de las subpoblaciones linfocitarias (SPL) para asistencia diagnóstica y monitoreo de las inmunodeficiencias primarias y adquiridas a través de las expresiones antigénicas de CD19 y CD20 para linfocitos B; CD2, CD3, CD4 y CD8 para linfocitos T; y CD56 y CD16 para identificación de células natural killer (NK). La CF ha revolucionado la manera como las células son identificadas y, a lo largo de los años, esa plataforma ha progresado con diversos avances en hardware y software que aspiran a mejorar el flujo de trabajo resultando en mayor productividad, calidad y reducción de costos. El Aquios CL Beckman Coulter (BC) es un ejemplo de ese avance, pues es un instrumento de automación completa en CF (llamado Load & Go flow cytometer) para cuantificación de SPL en la rutina diagnóstica. En este estudio el Aquios CL fue validado, y la cuantificación en números relativos y absolutos de las subpoblaciones linfocitarias tuvo una excelente correlación con los resultados obtenidos por la cuantificación en plataforma dupla realizada en el Cytomics FC500 (BC) y en el analizador automatizado de células Sysmex XE-2100.

RESUMO A citometria de fluxo (CF) é uma ferramenta importante para diagnóstico, prognóstico e acompanhamento terapêutico de diversas neoplasias hematológicas. Além disso, possibilita a quantificação das subpopulações linfocitárias (SPL) para assistência diagnóstica e monitoramento das imunodeficiências primárias e adquiridas por meio das expressões antigênicas de CD19 e CD20 para linfócitos B; CD2, CD3, CD4 e CD8 para linfócitos T; e CD56 e CD16 para identificação de células natural killer (NK). A técnica de CF revolucionou a maneira como as células são identificadas e, ao longo dos anos, essa plataforma tem progredido com diversos avanços em hardware e software que visam melhorar o fluxo de trabalho, resultando em maior produtividade, qualidade e redução de custos. O Aquios CL - Beckman Coulter (BC) é um exemplo desse avanço, pois é um equipamento de automação completa em CF (denominado Load & Go flow cytometer) para quantificação de SPL na rotina diagnóstica. Neste estudo, o Aquios CL foi validado, e a quantificação em números relativos e absolutos das subpopulações linfocitárias teve uma excelente correlação com os resultados obtidos pela quantificação em plataforma dupla realizada no Cytomics FC500 (BC) e no analisador automatizado de células Sysmex XE-2100.

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.

Effects of Shkbp1 deletion on mouse T lymphocyte subsets / 中国比较医学杂志

Objective Shkbp is also called Shkbp1,can competitively inhibit binding CIN85 and c-Cbl,thereby blocking the epidermal growth factor receptor (EGFR) endocytosis and degradation,to play a role in tumor promotion.This study aims to explore the changes in blood cell classification and T cell subsets in blood,bone marrow,and spleen in Shkbp1-deletion (Shkbp-1-/-) mice.Methods Shkbp-1-/-transgenic mice were identified by PCR genotyping.Blood cell classification was performed using an automatic classification system.Flow cytometry was used to detect the T lymphocyte subsets in the blood,bone marrow,and spleen of Shkbp-1-/-and control mice.Results Routine blood examination showed that neutrophils and eosinophils tended to increase and showing significant differences,and there was no significant difference in lymphocytes.The flow cytometry results showed that there was a decrease of CD4+CD8+ double positive cells and increase of bone marrow CD3+ and CD4+ cells in the control group.However,there was a decreasing trend of CD3+,CD4+,CD8+,and CD4+CD8+ cells in the spleen tissues.Conclusions Shkbp1 is involved in the maturation and differentiation of blood cells,and affects the number of immune cells.This study lays a foundation for the study of how Shkbp1 is involved in the differentiation of blood cells.

Relación cd4/cd8 como marcador de morbilidad en pacientes VIH (+) / CD4/CD8 Ratio as morbility marker in HIV (+) patients

Introducción: En pacientes VIH (+) se han descrito marcadores predictores de enfermedades asociadas a etapa SIDA, sin embargo no existe claridad respecto factores asociados enfermedades no SIDA. Una relación CD4/CD8 baja se ha identificado como marcador de inmunosenescencia y aumento de morbimortalidad en la población general, sin embargo aún está en estudio su utilidad en pacientes VIH (+). Objetivo: Determinar si una relación CD4/CD8 baja se asocia a mayor morbilidad no relacionada a etapa SIDA en pacientes VIH (+). Material y métodos: Estudio observacional de cohorte retrospectivo. Se seleccionaron pacientes VIH (+) que ingresaron un programa de vacunación contra VHB del Hospital Dr. Gustavo Fricke desde octubre de 2012. Se dividieron en grupos con relación CD4/CD8 < 0.6 y CD4/CD8 > 0.6 y se analizó la aparición de enfermedades no relacionadas a etapa SIDA en ambos grupos durante su seguimiento hasta mayo de 2016. Resultados: En la muestra de 79 pacientes, 54 (68%) tuvieron una relación CD4/CD8 < 0.6 y 25 (32%) tuvieron un CD4/CD8 > 0.6. La incidencia de enfermedades no relacionadas a etapa SIDA fue 39 (72%) pacientes en el grupo con relación CD4/CD8 baja y 13 (52%) en el grupo con relación CD4/CD8 alto (p=0.06). En 15 (19%) pacientes la relación CD4/CD8 disminuyó, esto se asoció a educación hasta enseñanza básica (p=0.01), viraje a carga viral detectable (p<0.01) y enfermedad hepática (p=0.02) Conclusión: La relación CD4/CD8 es un marcador emergente y prometedor, pero aún falta evidencia para determinar su utilidad.

Introduction: Although biomarkers predicting AIDS-associated pathology have been described, there is little clarity with respect to the markers for non AIDS-associated pathology. A low CD4/CD8 ratio has been seen to be a marker of immunesenescence and raised morbi-mortality in the general population, however its usefulness in HIV (+) patients is still being studied. Objective: To determine whether a low CD4/CD8 ratio is associated with increased AIDS-unrelated morbidity in the AIDS stage of HIV (+) patients. Materials and Methods: Observational study with retrospective cohort. HIV (+) patients were selected from patients admitted to a HBV vaccination program in Dr. Gustavo Fricke Hospital from October 2012 on. They were divided into two groups: CD4/CD8 < 0.6 and CD4/CD8 > 0.6 and followed until May 2016, analyzing the appearance of AIDS-unrelated illnesses in both groups. Results: In the 79 patient sample, 54 (68%) had CD4/CD8 ratio < 0.6 and 25 (32%) had a CD4/CD8 ratio > 0.6. The incidence of non AIDS-related illnesses in the AIDS stage was 39 (72%) in patients with a low CD4/CD8 ratio and 13 (52%) in the group with a high CD4/CD8 ratio (p=0.06). Conclusion: The CD4/CD8 ratio fell in 15 (19%) of patients, this being associated with primary education only, (p=0.01), virologic rebound (p<0.01) and liver disease.

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.

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.

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+ .

Double positive CD4+CD8+ T cells: key suppressive role in the production of autoantibodies in systemic lupus erythematosus.

Background & objectives: The presence of CD4+CD8+ (double positive) T cells (DPT) in the target organs of several autoimmune diseases has been reported. The aim of this study was to investigate the pathogenic role of DPT in systemic lupus erythematosus (SLE). Methods: A total of 175 SLE cases and 125 matched healthy controls were investigated for CD3+, CD4+, CD8+ lymphocytes and DPT by flow cytometry. Serum samples from SLE patients and controls were tested for antinuclear antibody (ANA), anti-double strain deoxyribonucleic acid (anti-dsDNA), anti-U1 ribonucleoprotein (anti-U1 RNP), anti-sjogren syndrome A (anti-SSA), anti-ribosomal P protein (anti-rib-P), anti-Smith (anti-Sm), anti-Sjogren syndrome B (anti-SSB), complement 3 (C3) and complement 4 (C4). Results: The DPT median and 5-95 per cent range of SLE cases and healthy controls were 0.50 [0.10-2.60] and 0.80 [0.20-2.74] respectively (P<0.001). SLE patients were divided into a ≥1:1000 subgroup and a <1:1000 subgroup according to the ANA titre. The DPT of the former subgroup was significantly lower than that of the latter (P=0.032). The DPT medians of positive subgroups with anti-dsDNA (P<0.001), anti-U1RNP (P=0.018), anti-SSA (P=0.021) or anti-rib-P (P=0.039) were also significantly lower than the negative subgroups. Likewise, DPT was significantly lower in SLE subgroups with low concentration of C3 or C4 than those with high concentration (P<0.006). Interpretation & conclusions: Our findings show that the DPT cells may play a key suppressive role in the production of autoantibodies in SLE. Direct evidence that DPT regulates the pathogenesis of SLE needs to be investigated in future work.

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.