title: Mycobacterium tuberculosis Antigen 85A induces Th-1 immune responses in systemic sarcoidosis.
abstract: Sarcoidosis is a granulomatous disease of unknown etiology, characterized by a Th-1 immunophenotype. Although humoral immune responses by sarcoidosis subjects to mycobacterial proteins have been detected, mycobacterial antigens capable of inducing cellular immune responses in sarcoidosis subjects have not been reported. We used the enzyme-linked immunospot assay to assess for recognition of the Mycobacterium tuberculosis mycolyl transferase, Antigen 85A, by peripheral blood mononuclear cells from 25 sarcoidosis subjects, 22 PPD- (purified protein derivative) healthy volunteers, and 16 PPD+ healthy subjects. Reactivity to Ag85A whole protein was observed in 15 of 25 sarcoidosis subjects compared to 2 of 22 PPD- subjects (p=0.0006, Fisher's exact test) and to 14 of 16 PPD+ subjects (p=0.084, Fisher's exact test). Monoclonal antibody against HLA-DR inhibited recognition. In addition to immune recognition of Ag85A whole protein, peptide-mapping studies identified four immunogenic Ag85A peptides, which induced Th-1 immune responses in individual sarcoidosis subjects, suggesting that multiple epitopes from a mycobacterial protein may have a role in sarcoidosis immunopathogenesis.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, 1161 21st Avenue, AA2200 MCN, Nashville, TN 37232, USA.
authors.forename: Rana
authors.initials: R
authors.lastname: Hajizadeh
authors.forename: Hiroe
authors.initials: H
authors.lastname: Sato
authors.forename: James
authors.initials: J
authors.lastname: Carlisle
authors.forename: Michele T
authors.initials: MT
authors.lastname: Nadaf
authors.forename: Whitney
authors.initials: W
authors.lastname: Evans
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Shepherd
authors.forename: Robert F
authors.initials: RF
authors.lastname: Miller
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.forename: Wonder Puryear
authors.initials: WP
authors.lastname: Drake
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000328:Adult; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D003710:Demography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007159:Immunologic Tests; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D012507:Sarcoidosis / Q000097:blood / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000097:blood / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D010446:Peptide Fragments; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis