MultipleMycobacteriumantigens induce interferon-γ production from sarcoidosis peripheral blood mononuclear cells

Abstract

Summary Studies

Evidence for Mycobacteria in Sarcoidosis

“…The authors reported high IFN-g production from PBMNs stimulated with whole recombinant Ag85A in 15 of 25 patients with sarcoidosis and in 2 of 22 PPD-negative healthy control subjects. The same group reported Th 1 responses to antigens from mycobacterial ESAT-6, mKatG, and SodA (96). In this study, BAL cells from pulmonary sarcoidosis responded more robustly to the mycobacterial antigens than did peripheral cells, adding to the evidence that antigen and antigen-responsive cells may cluster in areas of active disease.…”

“…To test if the antigenic KatG peptide associated with sarcoidosis was specific to mycobacteria, we performed a sequence analysis (F. Ramírez-Valle and S. Prystowsky, unpublished data). Whereas KatG protein is approximately 70% identical across several species of mycobacteria as well as other bacteria, including nocardia, the mKatG peptide 13 epitope tested by Drake and colleagues (92,96) is approximately 90% identical among most mycobacteria (using the SIM protein alignment tool; http://ca. expasy.org/tools/sim-prot.html).…”

“…These findings suggest the possibility that immune cells isolated from diseased lungs possess a general hyperreactivity that is not specific to mycobacterial antigens. However, Drake and colleagues detected mycobacterial antigen-evoked cellular immune responses in cells from patients with sarcoidosis who did not react to Trypanosoma brucei lysates (96) or the neoantigen keyhole limpet hemocyanin (93), demonstrating antigen specificity in the immune response.…”

Antigen-specific multifunctional T-cells in sarcoidosis patients with Löfgren’s syndrome

“…For example, it was shown that BAL cells from sarcoidosis patients reacted to mycobacterial antigens but not to keyhole limpet haemocyanin, demonstrating antigen specificity [13,28]. Likewise, peripheral blood cells from a majority of sarcoidosis patients responded to stimulation with mycobacterial antigens but not lysate from Trypanosoma brucei [29]. However, it would also be of interest to compare blood and BAL responses to a common nonspecific antigen, such as tetanus or Candida spp., to see if there is a general propensity of memory T-cells to accumulate in BAL fluid, or if this is particularly the case with mycobacteria-specific cells in sarcoidosis.…”

Genetics of Sarcoidosis

“…In contrast, smoking appears to be protective against sarcoidosis [14,15]. Infectious agents, particularly Mycobateria, are re-emerging as a potential antigen in sarcoidosis with studies detecting Mycobacteria proteins in tissues from sarcoidosis patients and T-cells from sarcoidosis patients responding to stimulation by Mycobacterial antigens [16][17][18][19][20][21][22][23]. Recent studies have also demonstrated an interaction between genetic markers and in vitro immune responses to Mycobacterial antigens further supporting the gene-environment interaction theory.…”