Department of Pneumology, Medical University of Gdansk, Debinki 7 Str., 80-211 Gdansk, Poland.
Hum Immunol. 2013 Jan;74(1):45-51. doi: 10.1016/j.humimm.2012.10.007. Epub 2012 Oct 16.
We demonstrated opposite presence of mycobacterial heat shock proteins (Mtb-hsp) 70 kDa, 65 kDa, 16 kDa in sera and lymph nodes in sarcoidosis (SA). Higher occurrence of serum Mtb-hsp70 than Mtb-hsp 65 and Mtb-hsp 16 could be caused by sequestration of Mtb-hsp 65 and Mtb-hsp 16 in circulating immune complexes (CIs). It is possible that in genetically different predisposed hosts, Mtb-hsp 16 induced by dose-dependent nitrate/nitrite (NOx) may be involved in latent tuberculosis (TB), active TB, or SA development. We evaluated Mtb-hsp 70, Mtb-hsp 65, Mtb-hsp 16 presence in precipitated CIs and serum NOx level in 20 SA patients, 19 TB patients, and 21 healthy volunteers using PEG precipitation, Western Blot, and Griess methods. We revealed higher NOx concentrations in SA and TB than in controls, but lower in SA than TB. Mtb-hsp 16, Mtb-hsp 65, and Mtb-hsp70 concentrations in precipitated CIs were higher in SA than in TB and controls. In all tested groups, Mtb-hsp 16 concentration was higher than Mtb-hsp70 and Mtb-hsp 65. We suggest that lower levels of NOx may induce a M. tuberculosis genetic dormancy program via higher Mtb-hsp 16 expression in SA. It seems that Mtb-hsp 16 may be more important than Mtb-hsp70 and Mtb-hsp 65 in CIs formation and initiate an autoimmune response in SA related to mycobacteria's stationary-phase.
我们在结节病(SA)患者的血清和淋巴结中证实了分枝杆菌热休克蛋白(Mtb-hsp)70 kDa、65 kDa、16 kDa 的相反存在。血清中 Mtb-hsp70 的出现频率高于 Mtb-hsp65 和 Mtb-hsp16,可能是由于 Mtb-hsp65 和 Mtb-hsp16 被循环免疫复合物(CIs)隔离。在具有遗传差异的易感性宿主中,由剂量依赖性硝酸盐/亚硝酸盐(NOx)诱导的 Mtb-hsp16 可能参与潜伏性结核病(TB)、活动性 TB 或 SA 的发展。我们使用 PEG 沉淀、Western Blot 和 Griess 方法评估了 20 名 SA 患者、19 名 TB 患者和 21 名健康志愿者血清中沉淀的 CIs 和血清中 Mtb-hsp70、Mtb-hsp65 和 Mtb-hsp16 的存在以及 NOx 水平。我们发现 SA 和 TB 患者的 NOx 浓度高于对照组,但 SA 患者的浓度低于 TB 患者。沉淀的 CIs 中 Mtb-hsp16、Mtb-hsp65 和 Mtb-hsp70 的浓度在 SA 患者中高于 TB 患者和对照组。在所有测试组中,Mtb-hsp16 的浓度均高于 Mtb-hsp70 和 Mtb-hsp65。我们认为,NOx 水平较低可能通过 SA 中 Mtb-hsp16 表达的增加诱导结核分枝杆菌的遗传休眠程序。似乎 Mtb-hsp16 在沉淀的 CIs 形成中比 Mtb-hsp70 和 Mtb-hsp65 更重要,并在与分枝杆菌静止期相关的 SA 中引发自身免疫反应。