title: Multiple Mycobacterium antigens induce interferon-gamma production from sarcoidosis peripheral blood mononuclear cells.
abstract: Studies of sarcoidosis immunology have noted oligoclonal T cell populations, suggesting cell-mediated immunity that is antigen-specific. Sarcoidosis immunology and pathology are most similar to mycobacterial infections. Mycobacterium tuberculosis infection in mice and humans reflects T helper 1 (Th1) immune responses to multiple cell wall and secreted antigens. We investigated if the oligoclonal immune response in individual sarcoidosis subjects could be elicited by multiple secreted mycobacterial antigens by performing ex vivo enzyme-linked immunospot assay (ELISPOT) on peripheral blood mononuclear cells (PBMC) from 30 sarcoidosis, 26 purified protein derivative negative (PPD-) control and 10 latent tuberculosis subjects (PPD+) to assess Th1 responses to mycobacterial superoxide dismutase A (sodA), catalase-peroxidase (katG) and early secreted antigenic target protein (ESAT-6). A significant difference was noted among the sarcoidosis and PPD- control subjects to ESAT-6 [12 of 30 versus one of 26 (P = 0.0014)], katG [nine of 30 versus none of 26 (P = 0.002)] and sodA [12 of 30 versus none of 26 (P = 0.002)]. There was no significant difference between sarcoidosis and PPD+ subjects. Twelve sarcoidosis subjects recognized two or more mycobacterial proteins, as well as multiple distinct epitopes within individual proteins. One sarcoidosis subject on whom we collected bronchoalveolar lavage (BAL) fluid and PBMC had no recognition of mycobacterial antigens using PBMC, but BAL fluid demonstrated strong Th1 immune responses to ESAT-6 and katG. Individual sarcoidosis subjects recognized not only multiple mycobacterial proteins, but multiple distinct peptides within a specific protein, thus demonstrating that multiple mycobacterial epitopes elicit the Th1 immune response observed. Immune responses by sarcoidosis T cells to mycobacterial proteins may have an important role in sarcoidosis pathogenesis.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: J
authors.initials: J
authors.lastname: Carlisle
authors.forename: W
authors.initials: W
authors.lastname: Evans
authors.forename: R
authors.initials: R
authors.lastname: Hajizadeh
authors.forename: M
authors.initials: M
authors.lastname: Nadaf
authors.forename: B
authors.initials: B
authors.lastname: Shepherd
authors.forename: R D
authors.initials: RD
authors.lastname: Ott
authors.forename: K
authors.initials: K
authors.lastname: Richter
authors.forename: W
authors.initials: W
authors.lastname: Drake
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D010544:Peroxidases / Q000276:immunology; D012507:Sarcoidosis / Q000276:immunology*; D013482:Superoxide Dismutase / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018984:Epitopes, T-Lymphocyte; D014373:Tuberculin; D007371:Interferon-gamma; D010544:Peroxidases; C081610:catalase-peroxidase, bacteria; C095500:SodA protein, Bacteria; D013482:Superoxide Dismutase