Is mycobacterial heat shock protein 16 kDa, a marker of the dormant stage of Mycobacterium tuberculosis, a sarcoid antigen?

Abstract

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.