Bobadilla-Del-Valle Miriam, Leal-Vega Francisco, Torres-Gonzalez Pedro, Ordaz-Vazquez Anabel, Garcia-Garcia Maria de Lourdes, Tovar-Vargas Ma de Los Angeles, Delgado-Sanchez Guadalupe, Guerra De Blas Paola Del Carmen, Wallis Robert S, Ponce-De-León Alfredo, Sifuentes-Osornio José
Laboratorio de Microbiologia Clinica, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.
Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Publica, Cuernavaca, Mexico.
Front Cell Infect Microbiol. 2021 May 18;11:640707. doi: 10.3389/fcimb.2021.640707. eCollection 2021.
The lack of efficient and cost-effective diagnostic tools contributes to poor control of tuberculosis in endemic countries. Moreover, host biological processes influence susceptibility, and infection resolution. It is well known that comorbidities such as type 2 diabetes mellitus (DM2) affect the host immune response, making individuals more susceptible to infection. Currently, there are no laboratory tools that can identify those subjects who have a higher risk of developing the disease. In this study, we used a whole blood mycobacterial growth inhibition assay to assess the immune response capacity to inhibit mycobacterial growth between healthy subjects and those living with DM2 with optimal and poor glycemic control. We also measured cytokine levels in the culture supernatant by cytokine bead arrays. We included 89 patients with DM2: 54 patients with optimal control (mean age 56.2 ± 11.75 years) and 35 patients with poor control (mean age 52.05 ± 9.94 years). We also included 44 healthy subjects as controls (mean age 42.12 ± 11.75 years). We compared the Δlog UFC (a value that represents the difference between mycobacterial growth in the control tube versus the subject's blood) between each group. Our results demonstrate that patients with DM2 had a lower capacity to inhibit growth (Δlog UFC DM2 subjects 0.9581 (-0.3897 to 2.495) Δlog UFC healthy subjects 0.7190 (-0.2678 to 2.098); p=0.013). Comparing subjects living with DM2 (optimal and poor glycemic control) healthy subjects, we found only significant differences between healthy subjects and patients poorly controlled (Δlog UFC optimal control group 0.876 (-0.3897 to 2.495); Δlog UFC poor control group 1.078 (0.068 to 2.33); Δlog UFC healthy subjects 0.7190 (-0.2678 to 2.098); p= 0.022). Therefore, glycemic control assessed by glycosylated hemoglobin values influences the capacity of the host to control the infection. Our results confirm that the whole blood mycobacterial growth inhibition assay has potential utility as an marker of immunological control in subjects living with DM2. This assay can be used to evaluate the immune response of each individual against , allowing clinicians to choose a more specific host-directed therapy.
缺乏高效且具成本效益的诊断工具导致结核病流行国家的结核病控制不佳。此外,宿主生物学过程会影响易感性和感染的消退。众所周知,2型糖尿病(DM2)等合并症会影响宿主免疫反应,使个体更容易感染。目前,尚无实验室工具能够识别那些患结核病风险较高的个体。在本研究中,我们使用全血分枝杆菌生长抑制试验来评估健康受试者与血糖控制良好和不佳的DM2患者之间抑制分枝杆菌生长的免疫反应能力。我们还通过细胞因子微珠阵列测量了培养上清液中的细胞因子水平。我们纳入了89例DM2患者:54例血糖控制良好的患者(平均年龄56.2±11.75岁)和35例血糖控制不佳的患者(平均年龄52.05±9.94岁)。我们还纳入了44名健康受试者作为对照(平均年龄42.12±11.75岁)。我们比较了每组之间的Δlog UFC(一个代表对照管中分枝杆菌生长与受试者血液中分枝杆菌生长差异的值)。我们的结果表明,DM2患者抑制生长的能力较低(DM2受试者的Δlog UFC为0.9581(-0.3897至2.495),健康受试者的Δlog UFC为0.7190(-0.2678至2.098);p = 0.013)。比较DM2患者(血糖控制良好和不佳)与健康受试者,我们发现仅健康受试者与血糖控制不佳的患者之间存在显著差异(血糖控制良好组的Δlog UFC为0.876(-0.3897至