Combined CD4/CD8 ratio in induced sputum and pulmonary function testing for non-invasive identification of sarcoidosis

Induced sputum is a useful noninvasive method for assessing parenchymal diseases. This retrospective study investigated its potential application in combination with functional parameters to differentiate sarcoidosis from non-sarcoid interstitial lung disease (NSA-ILD), especially when bronchoscopy is clinically contraindicated. All 120 study patients (67 sarcoidosis and 53 NSA-ILD) underwent both bronchoalveolar lavage (flexible fiberoptic video bronchoscope; Pentax, Japan) and induced sputum testing (3% NaCl, selecting plugs method, 300 cells differentially counted in Giemsa stained cytopreps). CD4/CD8 subsets were identified by a fluorescence-activator cell sorter. All patients underwent high-resolution computerized tomography and 103 of 120 underwent transbronchial biopsy. Multivariate logistic regression models were applied to the data to predict the probability of having the sarcoidosis as a function of the explanatory variables: Model I contained demographic and induced sputum data, and Model II included demographic data and combined sputum and pulmonary function test results. The area under the curve was 0.899 for induced sputum parameters alone and 0.914 for induced sputum and pulmonary function parameters. Conclusion: The results derived from the combination of noninvasive induced sputum approach can be used as predictors with high specificity and sensitivity in the differential diagnosis of sarcoidosis.     

CD4 and CD4/CD8 ratio progression in HIV-HCV infected patients after achievement of SVR

BackgroundIn HIV-HCV co-infected patients, the long-term effects of HCV eradication on HIV disease progression are still unclear.ObjectivesThis study aims to determine if CD4 and CD4/CD8 ratio slopes improved after anti-HCV treatment in patients achieving a sustained virological response (SVR).Study designA total of 116 HIV-HCV co-infected patients, previously treated with Peg-IFN/RBV, were divided into two groups: SVR (55 patients who had achieved SVR), and non-SVR (61 patients). Retrospective data before and after anti-HCV therapy were obtained for all patients, with a median 8 year-follow-up. Multilevel mixed models were fitted to assess the trends over time of FIB-4 score, APRI score, CD4, CD8 cell count and CD4/CD8 ratio.ResultsMedian HIV-infection duration, HCV-RNA and GGT baseline levels were higher in non-SVR compared to the SVR group. A significantly decreased FIB-4 (p < 0.001) and APRI trend (p < 0.001) after SVR was observed in SVR patients compared to those non-SVR. After adjustment for HIV duration, there was no significant difference between the two groups for absolute CD4 (p = 0.08) or percentage CD4 slope (p = 0.6) over time. The CD4/CD8 ratio trend also demonstrated a similar progressive increase in both groups (p = 0.2). During follow-up, six deaths were reported in the non-SVR group versus no death for the SVR group, while no difference in AIDS and non-AIDS events was observed.ConclusionsAchievement of SVR determines an important beneficial impact in terms of liver-related mortality and fibrosis regression, but does not seem to alter neither the slope of long term CD4 gain nor the CD4/CD8 ratio evolution in ART-treated HIV-HCV co-infected patients.     

Low CD4/CD8 T lymphocyte ratio in acute myocardial infarction.

T lymphocyte subsets were analysed using monoclonal antibodies and flow cytometry to determine whether myocardial infarction and cardiopulmonary resuscitation induce changes in these. Groups of 11 infarct patients and 10 patients with past cardiopulmonary resuscitation were compared with 11 age- and sex-matched controls and 12 sepsis patients. The differences in the CD4/CD8 ratios between the four groups were significant (F = 7.71, P = 0.001). The infarct patients had lower CD4/CD8 ratios (mean +/- s.d. 0.83 +/- 0.43) than the control (2.12 +/- 1.13; P = 0.001) or sepsis cases (1.76 +/- 1.05; P = 0.004), but their ratios did not differ from those of the resuscitation group (0.93 +/- 0.79, P = 0.84). The latter group also had lower ratios than the control (P = 0.003) and sepsis groups (P = 0.013). Most infarct patients had an on admission inverted CD4/CD8 ratio which usually returned to normal in the next 2 days. A permanently low CD4/CD8 ratio may be a poor sign prognostically after both myocardial infarction and resuscitation.     

Comparison of non-invasive fibrosis markers and classical liver biopsy in chronic hepatitis C

The aim of this study was to compare the results of nine non-invasive serum biomarkers with liver biopsies to predict liver fibrosis stage. HCV-RNA-positive, HCV genotype 1, treatment-naive patients with chronic HCV infections were included from 14 centers (n=77). The platelet count, AST/ALT ratio (AAR), cirrhosis discriminate score (CDS), FIB4, AST/platelet ratio index (APRI), age-platelet (AP) index, G?teborg University cirrhosis index (GUCI), FibroTest, and ActiTest were calculated and compared to histologic findings. All serum biomarkers, except AAR, were weakly or moderately correlated with liver biopsy results (ISHAK fibrosis score). The mean scores of FibroTest, FIB4, APRI, and AP index were significantly different between F0-F2 and F3-F4 groups and the negative predictive values (NPVs) of the F3-F4 group were 95%, 85%, 85%, and 83%, respectively, for these serum biomarkers. Our study suggests that serum biomarkers may help to diagnose significant fibrosis but inadequate to detect fibrosis in early stages. Although liver biopsy is still the gold standard to diagnose liver fibrosis, FibroTest, FIB4, APRI, or AP index may be used to exclude significant fibrosis with >80% NPV.     

A major quantitative trait locus for CD4-CD8 ratio is located on chromosome 11

CD4-CD8 ratio is an important diagnostic measure of immune system functioning. In particular, CD4-CD8 ratio predicts the time taken for progression of HIV infection to acquired immune deficiency syndrome (AIDS) and the long-term survival of AIDS patients. To map genes that regulate differences between healthy individuals in CD4-CD8 ratio, we typed 757 highly polymorphic microsatellite markers at an average spacing of approximately 5 cM across the genome in 405 pairs of dizygotic twins at ages 12, 14 and 16. We used multipoint variance components linkage analysis to test for linkage between marker loci and CD4-CD8 ratio at each age. We found suggestive evidence of linkage on chromosome 11p in 12-year-old twins (LOD=2.55, P=0.00031) and even stronger evidence of linkage in the same region at age 14 (LOD=3.51, P=0.00003). Possible candidate genes include CD5 and CD6, which encode cell membrane proteins involved in the positive selection of thymocytes. We also found suggestive evidence of linkage at other areas of the genome including regions on chromosomes 1, 3, 4, 5, 6, 12, 13, 15, 17 and 22.     

Modifications of CD4 T cells,CD4/CD8 ratio and serum levels of soluble CD14 in HIV-HCV-coinfected patients after sustained HCV response induced by direct-acting antiviral agents: influence of liver cirrhosis

European Journal of Clinical Microbiology & Infectious Diseases - To analyze the modifications of CD4 T cell, CD4/CD8 ratio, and serum levels of soluble CD14 (sCD14) in HIV/HCV-coinfected...     

CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia and not to hepatitis C virus genotypes in chronic hepatitis C.

The pathogenic mechanisms that lead to chronic hepatitis C are unknown. As hepatitis C virus (HCV) has been shown to induce T cell response, we assessed whether a particular T lymphocyte subset could be preferentially detected in the liver of patients with chronic hepatitis C in relation to viraemia or HCV genotypes. The immunophenotypes of liver-derived lymphocytes were analysed in 26 patients by flow cytometry and immunohistochemistry. Viraemia was quantified by branched DNA assay. Using this assay, HCV RNA was not detectable in six patients. HCV RNA was detected in 20 patients, and titres ranged from 8 to 137 x 10(6) Eq/ml. Genotyping was performed using a line probe assay. Type 1a, 1b, 2a, 3a and 4a were found to infect 2, 10, 2, 7 and 3 patients, respectively. The CD4+/CD8+ ratio of liver-derived lymphocytes was significantly higher (P < 0.01) in patients with detectable viraemia than in patients without detectable viraemia. In contrast, neither the percentage of gamma/delta T lymphocytes nor that of CD2+CD57+ cells was different in the groups. When comparing the CD4+/CD8+ ratio, the percentage of gamma/delta T lymphocytes or CD2+CD57+ cells according to genotype, the differences were not significant. These results suggest that the CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia but not to HCV genotypes in patients with chronic hepatitis C, and that T lymphocytes may be involved in the pathogenesis of liver lesions in chronic hepatitis C.     

Transient CD4/CD8 ratio inversion and aberrant immune activation during dengue virus infection

The immune status after dengue virus infection was studied in dengue patients from an outbreak of serotype 3 dengue virus infection in the southern part of Taiwan during November and December 1998. Consecutive blood samples from 29 dengue patients, of whom 21 had dengue fever and 8 had dengue hemorrhagic fever/dengue shock syndrome, were collected, and the immunophenotypes of the peripheral blood mononuclear cells were determined by flow cytometry. The early activation marker CD69 appeared on lymphocytes and monocytes at day 4 after the onset of fever, and declined afterward. However, a transient reverse in the CD4/CD8 ratio occurred at days 6-10 after the onset of fever. The CD4/CD8 ratio inversion was manifested in 10 of 29 dengue patients and was encountered more frequently in dengue hemorrhagic fever/dengue shock syndrome than in dengue fever patients. Analysis of the clinical blood cell count of these 10 cases showed that increase of immature neutrophils developed at fever days 5-6, CD4(dim) or CD8(dim) monocytosis at days 6-7, and atypical lymphocytosis at days 8-10 after the onset of fever. Serum IL-6 was found at either day 7 or day 9-11. The PHA-stimulated T-cell response was depressed as well. These changes in immune parameters indicate aberrant immune activation during dengue virus infection and might be involved in the pathogenesis of dengue virus infection.     

Serum hyaluronan: a marker of liver fibrosis in patients with chronic liver disease

The aim of this study was to evaluate the clinical significance of serum hyaluronan (HA) as a marker of liver fibrosis in patients with chronic liver disease. Serum HA was measured by an ELISA-based method in 28 patients with chronic hepatitis (CH), 43 patients with liver cirrhosis (LC), 57 patients with hepatocellular carcinoma (HCC) and 60 healthy controls. Mean serum HA concentration in patients with LC was 1,376.80 +/- 2,568.85 ng/ml which was significantly higher than those in patients with CH, HCC and the controls (575.93 +/- 732.58, and 426.36 +/- 687.33, and 117.86 +/- 311.11 ng/ml, respectively). Based on a ROC curve analysis, a cut-off point of 354 ng/ml discriminated between LC and other groups with a sensitivity, specificity and accuracy of 82.4%, 78.2%, and 80.2%, respectively. Mean HA concentrations were correlated with the degree of liver fibrosis, but not the grade of necroinflammatory activity. In patients with LC, the mean serum HA level was significantly increased in the Child C group (3,977.96 +/- 4,906.21 ng/ml) in comparison with the Child B and A groups (1,002.63 +/- 448.55, and 537.90 +/- 424.16 ng/ml, respectively). We conclude that serum HA concentrations reflect the extent of liver fibrosis and severity of cirrhosis. Thus, serum HA can be a diagnostic marker of liver fibrosis and cirrhosis in patients with chronic liver disease.     

广东HIV/AIDS患者舌象分析及其与CD4、CD8、CD4/CD8计数的相关性研究

目的分析广东HIV/AIDS患者的舌象规律及其与CD4、CD8、CD4/CD8计数的规律。方法对609例广东HIV/AIDS患者进行舌象分析和CD4、CD8T淋巴细胞检测,探讨其相关性。结果HIV/AIDS患者CD4、CD4/CD8比值均低于正常水平;两组淡红舌患者的CD4、CD4/CD8比值均高于其他4种舌色(淡白舌、红舌、暗舌、紫舌)(P<0.05);两组淡白舌患者的CD4、CD4/CD8比值均低于其他4种舌色(P<0.05);HIV/AIDS患者暗舌的比例(41.38%)均大于其他舌色,其次是红舌(35.47%)(P<0.05);HIV/AIDS患者以白腻苔(44.83%)为主,其次为黄腻苔(26.11%)、薄白苔(20.20%),少苔(3.45%)。结论舌象能客观反映HIV/AIDS患者身体免疫机能;广东HIV/AIDS患者多出现正气虚,夹瘀、夹痰化热的表现。     

慢性乙型肝炎患者CD4~+和CD8~+T细胞亚群的研究

目的:比较不同感染状态慢性乙型肝炎(CHB)患者外周血CD4+和CD8+T细胞亚群的差异。方法:收集CHB患者78例,根据感染状态分为乙型肝炎e抗原(HBeAg)阳性且肝功能正常、HBeAg阳性且肝功能异常和HBeAg阴性3组。13例健康志愿者(正常对照组)来自曙光医院体检中心。应用流式细胞术(FCM)检测不同感染状态CHB患者外周血中CD4+CD25+、CD8+CD28-、CD4+CD95+、CD8+CD95+细胞亚群的分布情况,并对各亚群分布情况与HBeAg和HBVD-NA水平的相关性进行分析。结果:与正常对照组相比,HBeAg(+)肝功能正常组的CD4+CD25+/CD4+和CD4+CD95+/CD4+明显升高(P<0.01,P<0.05),3个感染组CD8+CD28-/CD8+值均明显升高(P<0.01);与HBeAg(+)肝功能正常组相比,HBeAg(+)肝功能异常组和HBeAg(-)组的CD4+CD25+/CD4+明显降低(P<0.01),HBeAg(-)组CD8+CD95+/CD8+明显降低(P<0.05),HBeAg(+)肝功能异常组的CD8+CD95+/CD8+明显降低(P<0.01)。CD4+CD25+/CD4+,CD4+CD95+/CD4+与HBVDNA呈正相关(P<0.01,P<0.05),CD8+CD28-/CD8+与HBVDNA和HBeAg均呈正相关(P<0.01)。结论:CHB患者外周血中CD4+CD25+、CD8+CD28-T、CD4+CD95+细胞表达频率增加,可能对慢性乙肝病毒感染过程中的免疫耐受起一定作用。     

Flow cytometry CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication in chronic hepatitis B.

T lymphocytes have been assumed to play an essential role in tissue injury in patients with chronic hepatitis B. As hepatitis B virus (HBV) is considered as a major factor controlling liver inflammation, we assessed whether a particular T lymphocyte subset could be preferentially detected in the liver in accordance with viral replication. Liver-derived lymphocytes and peripheral blood lymphocytes were analysed by flow cytometry in 21 patients with histologically confirmed chronic hepatitis B without cirrhosis. Viral replication was quantified by hybridization of serum HBV DNA. Eleven patients exhibited an active viral replication with serum HBV DNA ranging from 10 to 388 pg/ml at the time of the liver biopsy, whereas 10 patients had no detectable serum HBV DNA. In patients exhibiting viral replication, CD4+/CD8+ ratios of liver-derived lymphocytes were significantly higher (P < 0.05) than those obtained in patients without viral replication. In contrast, the percentage of T cells expressing the gamma/delta receptor and that of CD2+/CD57+ cells were similar in both groups of patients. Furthermore, in patients exhibiting viral replication, CD4+CD8+ ratios of liver-derived lymphocytes correlated with serum HBV DNA levels (P < 0.001). No relationship between CD4+/CD8+ ratio of liver-derived and peripheral blood lymphocytes was observed. Our data indicate that, in patients with chronic hepatitis B, the CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication. This suggests that in situ helper/inducer CD4+ T lymphocytes may positively regulate the cytotoxic T cell activity in patients with HBV-related chronic hepatitis.     

CD8 alpha is an activation marker for a subset of peripheral CD4 T cells

Rat CD4 T lymphocytes express CD8 alpha upon activation. Here, we show that double-positive cells express CD8 alpha alpha homodimers, and we study their phenotype and function. Most activated CD4(+) lymphocytes expressing CD8 alpha are recent thymic emigrants. Accordingly, most activated CD4 single-positive thymocytes express CD8 alpha, and thymectomy and aging decrease the frequency of CD4(+)CD8 alpha(+) lymphocytes. However, CD8 induction is not restricted to CD4(+) recent thymic emigrants. CD4(+)CD8 alpha(+) and CD4(+)CD8 alpha(-)cells were generated in vitro from naive or from primed donors and, to study their function, were transferred to normal rats. Both cell types helped primary humoral responses, but only CD4(+)CD8 alpha(-) cells promoted secondary responses. Thus, memory CD4 T cells mediating antibody responses and some naive CD4(+) lymphocytes do not express CD8 alpha. In addition, CD4(+)CD8 alpha(+) cells produce mainly Th1 cytokines while CD4(+)CD8 alpha(-) cells produce IL-10 and showed a sustained proliferative response. Hence, CD8 alpha expression after activation distinguishes two distinct CD4 T cell subsets.     

Activation-induced marker assays for identification of Trypanosoma cruzi-specific CD4 or CD8 T cells in chronic Chagas disease patients

Antigen-specific T cells are central to the adaptive immune response against T. cruzi infection and underpin the efficacy of on-going vaccine strategies. In this context, the present study focuses on T-cell assays that define the parasite-specificity on the basis of upregulation of TCR stimulation-induced surface markers. For this purpose, we tested different dual marker combinations (OX40, CD25, CD40L, CD137, CD69, PD-L1, CD11a, CD49d, HLA-DR, CD38) to reliably identify activated CD4⁺ and CD8⁺ T-cell populations from PBMCs of chronic Chagas disease (CCD) patients after 12 or 24 h of stimulation with T. cruzi lysate. Results demonstrated that activation-induced markers (AIM) assays combining the expression of OX40, CD25, CD40L, CD137, CD69 and/or PD-L1 surface markers are efficient at detecting T. cruzi-specific CD4⁺ T cells in CCD patients, in comparison to non-infected donors, after both stimulation times. For CD8⁺ T cells, only PD-L1/OX40 after 24 h of antigen exposure resulted to be useful to track a parasite-specific response. We also demonstrated that the agnostic activation is mediated by different T. cruzi strains, such as Dm28c, CL Brener or Sylvio. Additionally, we successfully used this approach to identify the phenotype of activated T lymphocytes based on the expression of CD45RA and CCR7. Overall, our results show that different combinations of AIM markers represent an effective and simple tool for the detection of T. cruzi-specific CD4⁺ and CD8⁺ T cells.     

INR-to-platelet ratio (INPR) as a novel noninvasive index for predicting liver fibrosis in chronic hepatitis B

Objective: We aimed to investigate whether a novel noninvasive index, i.e., the international normalized ratio-to-platelet ratio (INPR), was a variable in determining liver fibrosis stage in patients with chronic hepatitis B (CHB).Methods: A total of 543 treatment-naïve CHB patients were retrospectively enrolled. Liver histology was assessed according to the Metavir scoring scheme. All common demographic and clinical parameters were analyzed.Results: Based on routine clinical parameters (age, sex, HBeAg status, HBV DNA, hematological parameters, coagulation index, and liver biochemical indicators), a novel index, i.e., the INR-to-platelet ratio (INPR), was developed to magnify the unfavorable effects of liver fibrosis on INR and platelets. The AUCs of INPR for predicting significant fibrosis, advanced fibrosis, and cirrhosis were 0.74, 0.76 and 0.86, respectively. Compared with APRI, FIB-4, and GPR, the INPR had comparable predictive efficacy for significant fibrosis and better predictive performance for advanced fibrosis and cirrhosis.Conclusion: INPR could be an accurate, easily calculated and inexpensive index to assess liver fibrosis in patients with CHB. Further studies are needed to verify this indicator and compare it with other noninvasive methods for predicting liver fibrosis in CHB patients.     

CD4/CD8 ratio,comorbidities, and aging in treated HIV infected individuals on viral suppression

The progression of the human immunodeficiency virus (HIV) infection to acquired immunodeficiency syndrome (AIDS) can be efficiently interrupted by antiretroviral therapy (ART). However, even successfully treated HIV-infected individuals are prone to develop non-AIDS-related diseases that affect the metabolism and several organs and systems. Biomarkers that predict the occurrence of comorbidities may help develop preventive measures. Current research shows that CD4⁺ T cell counts and viral load do not predict the development of non-AIDS-related diseases. The CD4/CD8 ratio has been indicated as a suitable marker of persistent immune dysfunction and the occurrence of non-AIDS-related events in treated HIV-positive patients. In this study, we explored the relationship between CD4/CD8 ratios, comorbidities, and aging in ART-treated HIV patients on viral suppression. We collected and evaluated data from 352 HIV-positive adults who were virologically suppressed (<40 copies/mL) on ART and with CD4 counts above 350 cells/mm³. The median age for participants was 46 years, 218 individuals had at least one comorbidity, and 239 had inverted CD4/CD8 ratios (<1). Current CD4/CD8 ratios were predicted by baseline CD4/CD8 ratios and nadir CD4 counts. Despite the high rates of inverted CD4/CD8 ratios and prevalence of comorbidities, no association between them was observed. The prevalence of comorbidities was significantly higher in older individuals, though aging alone did not explain the rate of all individual comorbidities. Low CD4/CD8 ratios were linked to neurocognitive disorders, suggesting that persistent T cell dysfunction contributes to neurocognitive decline.     

Dichotomy of two CD8+ lymphocyte subsets in HIV infection. Depletion of CD8+ CD3- and expansion of CD8+ CD3+ subsets: consequence on the CD4/CD8 ratio.

In order to highlight the underlying mechanism(s) of the CD8 lymphocyte expansion in the HIV infection, two distinct CD8 subsets were analysed: T CD8bright+ CD3+ with MHC-restricted activity, and non-T CD8dim+ CD3-, which performs natural killer (NK) activity. It consists of a cross-sectional study including 168 HIV-infected patients (74 CDC stage II, 48 CDC stage III and 46 CDC stage IV) compared among them and to 60 healthy individuals. We observed an expansion of CD8+ CD3+ cells which masks a depletion of CD8+ CD3-. The comparative study showed that the expansion of the CD8+ CD3+ is relatively higher than that of total CD8+ lymphocytes and that the depletion of the CD8+ CD3- subset is severe, begins early and remains constant through the HIV progression. The comparison of CD4/CD8 and CD4/CD8+ CD3+ ratios showed that the latter could possibly be a better indicator in the HIV infection. The mechanism of inverted CD4/CD8 ratio in healthy individuals was also clarified. The CD8+ CD3+, CD8+ CD3- and CD4/CD8+ CD3+ parameters would be more specific markers than total CD8 and CD4/CD8 ratio especially in therapy trials.