Differences in PPD- and mitogen-induced T-cell activation marker expression characterize immunopathology in acute tuberculosis patients.

Impaired T-cell responses to mitogens and high T-cell activation marker (TAM) expression on Mycobacterium tuberculosis-specific T-cells characterize immunopathology in patients with tuberculosis (TB). In a study of patients with TB (n = 60) and asymptomatic contacts (controls, n = 37), we found that TB patients had higher CD38+ T-cell proportions specific for M. tuberculosis protein (PPDMtb), yet total proportions of PPDMtb-specific T-cells were comparable. Notably, both activated (CD38+) and total IFN-γ+ T-cells from TB patients had lower mitogen (phytohemagglutinin, PHA)-induced responses. This impaired mitogen response improved the classification efficacy of the TAM-TB assay, especially employing the PPD/PHA-induced T-cell ratio.

Diminished Interleukin-7 receptor expression on T-cell subsets in tuberculosis patients.

Immunopathology in human tuberculosis affects T-cell phenotype and functions. Previous studies identified impaired T-cell sensitivity to Interleukin (IL)-7 accompanied by lower IL-7 receptor α-chain (IL-7Rα) expression in patients with acute tuberculosis. In the present study, we characterized affected T-cell subsets and determined the influence of tuberculosis disease severity and treatment response. Tuberculosis patients (n = 89) as well as age- and gender-matched asymptomatic contacts (controls, n = 47) were recruited in Ghana. Mycobacterium (M.) tuberculosis sputum burden was monitored prior to and during treatment. Blood samples from all patients and controls were analyzed for IL-7Rα expression and T-cell markers by multi-colour flow cytometry. CD4+ and CD8+ T-cells of tuberculosis patients showed generally lower IL-7Rα expression as compared to controls. Concomitantly, tuberculosis patients had higher proportions of naïve and lower proportions of memory CD4+ T-cells. Notably, a subset of CD27 positive central memory T-cells (Tcm), which lacked IL-7Rα expression was enriched in tuberculosis patients as compared to controls. M. tuberculosis sputum burden was not associated with differences in IL-7Rα expression. Treatment duration and response showed no clear effects although IL-7Rα expression patterns were highly variable. These results suggested generally impaired generation of memory CD4+ T-cells and enrichment of a Tcm subset without IL-7Rα expression in patients with tuberculosis.

Anthropometric indices and their cut-off points in relation to type 2 diabetes among Ghanaian migrants and non-migrants: The RODAM study.

AIMS: To compare body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) as determinants of type 2 diabetes (T2DM) and determine optimal cut-offs in a sub-Saharan African population. METHODS: Data from the RODAM study including Ghanaians aged 25-70 living in rural Ghana, urban Ghana and Europe were used. Logistic regression was used to assess associations between BMI, WC, WHR and T2DM status, by sex and site. Area under the curve (AUC) were constructed to discriminate between indices and establish performance and cut-off values. RESULTS: WHR had the strongest association with T2DM in men and women across sites, except for rural men. The highest adjusted odds ratio (aOR) and AUC were in rural women for WHR (aOR = 2.09, 95%CI = 1.47-2.99; AUC = 0.71). Among migrants, WHR had higher AUCs compared with BMI (p < 0.01) and WC (p < 0.05). Cut-offs for BMI and WC in men were lower compared with the WHO reference across sites (WC: 85.4-93.7 vs 102 cm, BMI: 23.1-28.2 vs 30.0 kg/m2). CONCLUSIONS: WHR outperformed BMI and WC as anthropometric indices in relation to T2DM among Ghanaian migrants. The lower BMI and WC cut-offs for T2DM than WHO established standards, highlights the need for African specific cut-offs to avoid missing high risk populations.

Increased metformin dosage suppresses pro-inflammatory cytokine levels in systemic circulation and might contribute to its beneficial effects.

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder, characterized by persistent elevation of blood glucose either due to insulin resistance or insulin insufficiency. Metformin is the recommended first choice of drug for the management of T2DM and is known to improve insulin sensitivity and prevents hyperglycemia by reducing chronic inflammation. T-helper type 1 (Th1) and type 17 (Th17) cells, are important pro-inflammatory CD4+ T cell subsets secreting TNF-α, and INF-γ (Th1), and interleukin 17 (Th17). These cytokines have been shown to play a crucial role in inflammation, insulin resistance, and the development of T2DM. Here, we explore the effect of different metformin dosages on pro-inflammatory cytokine (TNF-α, INF-γ, GM-CSF and IL-17) levels in systemic circulation among T2DM patients in Ghana, since inflammatory responses and cytokines play significant roles in the pathogenesis and progression of T2DM patients on metformin. Two hundred and nine (209) consenting T2DM patients receiving treatment at the Diabetic unit of the Komfo Anokye Teaching Hospital (KATH) in the Ashanti region of Ghana were recruited in a hospital-based cross-sectional study design. Blood samples were collected and serum obtained from each participant were analyzed for the concentrations of TNF-α, INF-γ, GM-CSF and IL-17 cytokine levels by solid-phase sandwich ELISA. We observed that participants on 3000 mg/day dose of metformin had significantly lower levels of TNF-α (p < .001) and IFN-γ (p = .014) compared to those on other dosages (1000 mg and 2000 mg/day). However, GM-CSF and IL-17 levels were not affected by increased metformin dosages. After adjusting for age, gender, dose and duration of metformin use, we observed that participants who took higher doses of metformin had significantly reduced levels of TNF-α (ß = -0.0297, 95% CI = (-0.005 to -0.002) p < .001. Metformin dosage independently predicted reduced TNF-α levels with 14.4% variations in the metformin dosage levels. Increased metformin dosage suppresses TNF-α levels in systemic circulation and hence might contribute to its beneficial effects.

An Analysis of Anthropometric Indicators and Modifiable Lifestyle Parameters Associated with Hypertensive Nephropathy.

The surge in prevalence of chronic noncommunicable diseases like hypertension and chronic kidney disease has been linked with modifiable lifestyle practices and increased body fat. This study sought to compare the association between different modifiable lifestyle practices, adiposity indices, renal function parameters, and hypertension as well as the predictive implications for levels of these parameters in target cardiac organ damage among an urban Ghanaian hypertensive population. Using a hospital-based case-control study design, 241 Ghanaian indigenes from the Kumasi metropolis were recruited for this study. The case group was made up of 180 hypertensives and 61 normotensives served as controls. In addition to sociodemographic data, standard haemodynamic, anthropometric, renal function, and cardiac organ damage assessments were done. The prevalence of chronic kidney disease (CKD) ranged from 13.3% to 16.6% depending on the equation used in estimating the glomerular filtration rate (eGFR). Percentage cluster distribution by chronic kidney disease was observed to be significantly tilted toward the upper quartiles (3rd and 4th) of the haemodynamic parameters measured. Chronic kidney disease was significantly higher among self-reported smokers and alcoholic hypertensives. In this urban population, adiposity was associated with hypertension and renal insufficiency. Chronic kidney disease was associated with hypertension and cardiac abnormalities.