ABSTRACT
Aging influences the susceptibility and prognosis to various infectious diseases including tuberculosis (TB). Despite the impairment of T-cell function and immunity in older individuals, the mechanism for the higher incidence of TB in the elderly remains largely unknown. Here, we evaluated the age-associated immune alterations, particularly in effector and Treg responses in pulmonary TB patients. We also evaluated the impact of redox status and its modulation with N-acetyl-cysteine (NAC) in elderly TB. Higher frequency of Treg cells and reduced IFN-γ positive T cells were observed among older TB patients. The elevated number of Treg cells correlated tightly with bacillary load (i.e. disease severity); which declined significantly in response to successful anti-tubercular treatment. We could rescue Myobacterium tuberculosis-specific effector T cell (Th1) responses through various in vitro approaches, for example, Treg cell depletion and co-culture experiments, blocking experiments using antibodies against IL-10, TGF-ß, and programmed death-1 (PD-1) as well as NAC supplementation. We report old age-associated enrichment of Treg cells and suppression of M. tuberculosis-specific effector T (Th1) cell immune responses. Monitoring these immune imbalances in older patients may assist in immune potentiation through selectively targeting Treg cells and/or optimizing redox status by NAC supplementation.
Subject(s)
T-Lymphocytes, Regulatory/immunology , Tuberculosis, Pulmonary/immunology , Acetylcysteine/pharmacology , Adolescent , Adult , Age Factors , Aged , Cytokines/analysis , Cytokines/physiology , Female , Humans , Male , Middle Aged , Oxidation-Reduction , Oxidative Stress , Programmed Cell Death 1 Receptor/physiology , Th1 Cells/immunology , Transforming Growth Factor beta/physiology , Tuberculosis, Pulmonary/metabolism , Young AdultABSTRACT
BACKGROUND: Although achalasia patients are undernourished, studies are scant. We studied: (i) the frequency of malnutrition among these patients and (ii) the effect of pneumatic dilatation (PD) on malnutrition. METHODS: A total of 70 adult achalasia patients and 70 healthy controls were evaluated through dietary recall, anthropometry, and biochemical parameters, and patients were reevaluated 6 months after PD. RESULTS: Patients had lower intake of calories (median, interquartile range [IQR]: 1835.0 [1682.5-1915.0] vs 2071.5 [1950-2276.2] kcal/day, P < 0.001), protein (40.9 [36.3-42.2] vs 52.9 [45.7-62] g/day, P < 0.001), calcium (310 [192.5-392.4] vs 477.5 [350-560] mg/day, P < 0.001), and iron (6.7 [4.7-8.8] vs 10.1 [7.5-11.50] mg/day, P < 0.001) than controls. Patients had lower body mass index (BMI: 19.6 [16.6-22] vs 22.8 [19.5,29.1], P < 0.001), midarm circumference (MAMC; 20 [17.5-23] vs 24.1 [21.4-28.5], P < 0.001), biceps (BSFT; 3.1 [1.9-3.9] vs 5.5 [3.8-9.2] mm, P < 0.001), triceps' skin fold thickness (TSFT; 5 [2.4-7] vs 7.8 [5.1-9.4] mm, P < 0.001), serum protein (7.2 ± 0.8 vs 7.6 ± 0.8 g/dL, P = 0.005), and albumin (4.0 [3.5-4.4] vs 4.1 [3.9-4.2] g/dL, P = 0.009). PD increased calories (1803 [950-2400] vs 2050 [1470-2950] kcal/day), protein intake (41.0 [22-70] vs 45.0 [37.5-80.0] gm/day), BMI (19.6 [12.8-30.0] vs 22.2[15.9-30.0] P = 0.001 for all), and MAMC (21 [14.1-32.0] vs 24.2 [15-32.0] cm, P = 0.03). Reduced intake was a determinant of malnutrition. CONCLUSIONS: Malnutrition is common in achalasia patients, and PD improved it.