Department of Pulmonology, Medical University of Gdansk, 80-210 Gdansk, Poland.
Int J Mol Sci. 2023 Mar 7;24(6):5084. doi: 10.3390/ijms24065084.
Pathological similarities between sarcoidosis (SA) and tuberculosis (TB) suggest the role of mycobacterial antigens in the etiopathogenesis of SA. The Dubaniewicz group revealed that not whole mycobacteria, but Mtb-HSP70, Mtb-HSP 65, and Mtb-HSP16 were detected in the lymph nodes, sera, and precipitated immune complexes in patients with SA and TB. In SA, the Mtb-HSP16 concentration was higher than that of Mtb-HSP70 and that of Mtb-HSP65, whereas in TB, the Mtb-HSP16 level was increased vs. Mtb-HSP70. A high Mtb-HSP16 level, induced by low dose-dependent nitrate/nitrite (NOx), may develop a mycobacterial or propionibacterial genetic dormancy program in SA. In contrast to TB, increased peroxynitrite concentration in supernatants of peripheral blood mononuclear cell cultures treated with Mtb-HSP may explain the low level of NOx detected in SA. In contrast to TB, monocytes in SA were resistant to Mtb-HSP-induced apoptosis, and CD4T cell apoptosis was increased. Mtb-HSP-induced apoptosis of CD8T cells was reduced in all tested groups. In Mtb-HSP-stimulated T cells, lower CD8γδIL-4T cell frequency with increased TNF-α,IL-6,IL-10 and decreased INF-γ,IL-2,IL-4 production were present in SA, as opposed to an increased presence of CD4γδTCR cells with increased TNF-α,IL-6 levels in TB, vs. controls. Mtb-HSP modulating the level of co-stimulatory molecules, regulatory cells, apoptosis, clonal deletion, epitope spread, polyclonal activation and molecular mimicry between human and microbial HSPs may also participate in the induction of autoimmunity, considered in SA. In conclusion, in different genetically predisposed hosts, the same antigens, e.g., Mtb-HSP, may induce the development of TB or SA, including an autoimmune response in sarcoidosis.
结节病（SA）和结核病（TB）之间的病理相似性表明分枝杆菌抗原在 SA 的发病机制中起作用。Dubaniewicz 小组发现，在 SA 和 TB 患者的淋巴结、血清和沉淀免疫复合物中检测到的不是完整的分枝杆菌，而是 Mtb-HSP70、Mtb-HSP65 和 Mtb-HSP16。在 SA 中，Mtb-HSP16 浓度高于 Mtb-HSP70 和 Mtb-HSP65，而在 TB 中，Mtb-HSP16 水平高于 Mtb-HSP70。由低剂量依赖性硝酸盐/亚硝酸盐（NOx）诱导的高 Mtb-HSP16 水平可能在 SA 中发展出分枝杆菌或丙酸杆菌遗传休眠程序。与 TB 不同，用 Mtb-HSP 处理的外周血单核细胞培养物上清液中过氧亚硝酸盐浓度的增加可能解释了在 SA 中检测到的低水平 NOx。与 TB 不同，SA 中的单核细胞对 Mtb-HSP 诱导的凋亡具有抗性，并且 CD4T 细胞凋亡增加。在所有测试组中，Mtb-HSP 诱导的 CD8T 细胞凋亡减少。在 Mtb-HSP 刺激的 T 细胞中，与对照相比，SA 中存在较低频率的 CD8γδIL-4T 细胞，同时 TNF-α、IL-6、IL-10 增加，而 IFN-γ、IL-2、IL-4 减少，而在 TB 中，与对照相比，存在增加的 CD4γδTCR 细胞和 TNF-α、IL-6 水平增加。Mtb-HSP 调节共刺激分子、调节细胞、凋亡、克隆删除、表位扩展、多克隆激活和人类和微生物 HSP 之间的分子模拟的水平也可能参与 SA 中的自身免疫诱导。总之，在不同遗传易感性的宿主中，相同的抗原，例如 Mtb-HSP，可能会导致 TB 或 SA 的发展，包括 SA 中的自身免疫反应。
