Africa Health Research Institute (AHRI), Durban, South Africa.
College of Health Sciences, School of Laboratory Medicine & Medical Sciences, University of KwaZulu Natal, Durban, South Africa.
Front Immunol. 2023 May 29;14:1151528. doi: 10.3389/fimmu.2023.1151528. eCollection 2023.
The rising global burden of metabolic disease impacts the control of endemic tuberculosis (TB) in many regions, as persons with diabetes mellitus (DM) are up to three times more likely to develop active TB than those without DM. Active TB can also promote glucose intolerance during both acute infection and over a longer term, potentially driven by aspects of the immune response. Identifying patients likely to have persistent hyperglycemia following TB treatment would enable closer monitoring and care, and an improved understanding of underlying immunometabolic dysregulation.
We measured the relationship of plasma cytokine levels, T cell phenotypes and functional responses with the change in hemoglobin A1c (HbA1c) before and after treatment of pulmonary TB in a prospective observational cohort in Durban, South Africa. Participants were stratified based on stable/increased HbA1c (n = 16) versus decreased HbA1c (n = 46) levels from treatment initiation to 12 month follow-up.
CD62 P-selectin was up- (1.5-fold) and IL-10 downregulated (0.85-fold) in plasma among individuals whose HbA1c remained stable/increased during TB treatment. This was accompanied by increased pro-inflammatory TB-specific IL-17 production (Th17). In addition, Th1 responses were upregulated in this group, including TNF-α production and CX3CR1 expression, with decreased IL-4 and IL-13 production. Finally, the TNF-α+ IFNγ+ CD8+ T cells were associated with stable/increased HbA1c. These changes were all significantly different in the stable/increased HbA1c relative to the decreased HbA1c group.
Overall, these data suggest that patients with stable/increased HbA1c had an increased pro-inflammatory state. Persistent inflammation and elevated T cell activity in individuals with unresolved dysglycemia following TB treatment may indicate failure to fully resolve infection or may promote persistent dysglycemia in these individuals, and further studies are needed to explore potential mechanisms.
代谢性疾病在全球的负担不断增加，这对许多地区的地方性结核病（TB）控制产生了影响，因为糖尿病患者（DM）患活动性 TB 的可能性比非 DM 患者高 2-3 倍。活动性 TB 也可能在急性感染和长期感染过程中导致葡萄糖不耐受，这可能是由免疫反应的某些方面驱动的。识别出在 TB 治疗后可能持续存在高血糖的患者，将有助于进行更密切的监测和护理，并深入了解潜在的免疫代谢失调。
我们在南非德班的一项前瞻性观察队列中，测量了血浆细胞因子水平、T 细胞表型和功能反应与治疗开始后 12 个月内治疗肺结核前后血红蛋白 A1c（HbA1c）变化的关系。参与者根据治疗开始时 HbA1c 稳定/升高（n = 16）与降低（n = 46）进行分层。
在 HbA1c 在 TB 治疗过程中保持稳定/升高的个体中，血浆中的 CD62 P-选择素增加（1.5 倍），IL-10 下调（0.85 倍）。这伴随着促炎性 TB 特异性 IL-17 产生（Th17）增加。此外，在该组中，Th1 反应上调，包括 TNF-α 产生和 CX3CR1 表达，同时 IL-4 和 IL-13 产生减少。最后，TNF-α+ IFNγ+ CD8+ T 细胞与 HbA1c 稳定/升高相关。与 HbA1c 降低组相比，这些变化在 HbA1c 稳定/升高组中均显著不同。
总的来说，这些数据表明，HbA1c 稳定/升高的患者存在促炎状态增加。TB 治疗后血糖未得到充分控制的个体中持续的炎症和升高的 T 细胞活性，可能表明感染未得到完全解决，或者可能促进这些个体持续的血糖紊乱，需要进一步研究探索潜在的机制。
