Bio-profiling of TB patients with and without Type 2 Diabetes before and during anti-tuberculosis drug (ATD) therapy

[摘要] BackgroundPatients with type 2 diabetes (DM2) are three times more likely to acquire active tuberculosis (TB) compared to otherwise healthy people. TB-DM2 comorbidity is characterized by poor TB treatment outcomes, increased risk of failure and relapse. The exact mechanisms of increased susceptibility of diabetics to TB are not well understood, but it is thought that hyperglycaemia is associated with an impairment of the innate and adaptive immune response.AimTo assess soluble (cytokines) and cellular (T-cell subsets) immunological markers of treatment response in TB patients with and without DM2 and their association with glycaemic control.Materials and Methods Serum cytokine concentrations were measured by means of the Luminex assay in 14 TB and 11 TB-DM2 patients at Baseline, Month 2 and Month 6. The HO-1 levels were measured from serum samples by means of ELISA in 40 TB and 20 TB-DM2 patients at Baseline, Week 2, Month 2 and Month 6. The frequency of different T-cell subsets (central memory, naïve, effector memory and terminally differentiated effector memory T cells) was established in 8 healthy controls, 13 DM2, 18 TB and 23 TB-DM2 patients at Baseline, Month 2 and Month 6 using flow cytometry.ResultsThroughout treatment pro- and anti-inflammatory cytokine concentrations were increased in serum of TB-DM2 patients when compared to TB patients. Fibrinogen and Procalcitonin were higher in TB patients compared to the TB-DM2 patients at the end of treatment. Various cytokines (IL-1β, IL-4, IL-6, IL-7, IL-8, IL-9, G-CSF, GM-CSF, MCP-1(MCAF) and IFN-γ) and growth factors (VEGF and PDGF) exhibited positive correlation at baseline with HbA1c and random blood glucose, respectively. The frequencies of CD4+ naïve T cells increased from Baseline and Month 2 in TB patients. In contrast CD4+ and CD8+ naïve T cells decreased over time in the TB-DM2 patients. CD4+ T CM cells increased over time in TB-DM2 patients. Activated CD8+ naïve T cells increased over time in both TB and TB-DM2 patients while the terminally differentiated effector memory T cells decreased in both groups of study patients over time. No significant changes were observed in any CD8+ T cell subset in both groups of study patients.ConclusionThe present study reveals that TB-DM2 patients have altered cytokine production at baseline and throughout treatment which may be linked to chronic inflammation associated with obesity and diabetes. Glycaemic control displays an influence in cytokine production shown in TB-DM2 patients. The frequencies of T cell subsets is altered in TB-DM2 patients and changes throughout treatment. These results show that TB-DM2 patients are characterised by changes in the adaptive immune system, which may contribute to poor treatment outcomes.

[发布机构] Stellenbosch University