Mycobacterial catalase-peroxidase is a tissue antigen and target of the adaptive immune response in systemic sarcoidosis.
Sarcoidosis is a disease of unknown etiology characterized by noncaseating epithelioid granulomas, oligoclonal CD4(+) T cell infiltrates, and immune complex formation. To identify pathogenic antigens relevant to immune-mediated granulomatous inflammation in sarcoidosis, we used a limited proteomics approach to detect tissue antigens that were poorly soluble in neutral detergent and resistant to protease digestion, consistent with the known biochemical properties of granuloma-inducing sarcoidosis tissue extracts. Tissue antigens with these characteristics were detected with immunoglobulin (Ig)G or F(ab')(2) fragments from the sera of sarcoidosis patients in 9 of 12 (75%) sarcoidosis tissues (150-160, 80, or 60-64 kD) but only 3 of 22 (14%) control tissues (all 62-64 kD; P = 0.0006). Matrix-assisted laser desorption/ionization time of flight mass spectrometry identified Mycobacterium tuberculosis catalase-peroxidase (mKatG) as one of these tissue antigens. Protein immunoblotting using anti-mKatG monoclonal antibodies independently confirmed the presence of mKatG in 5 of 9 (55%) sarcoidosis tissues but in none of 14 control tissues (P = 0.0037). IgG antibodies to recombinant mKatG were detected in the sera of 12 of 25 (48%) sarcoidosis patients compared with 0 of 11 (0%) purified protein derivative (PPD)(-) (P = 0.0059) and 4 of 10 (40%) PPD(+) (P = 0.7233) control subjects, suggesting that remnant mycobacterial catalase-peroxidase is one target of the adaptive immune response driving granulomatous inflammation in sarcoidosis.
Song
Zhimin
Z
Division of Pulmonary and Critical Care Medicine, Department of Medicine, The Johns Hopkins University Bloomberg School of Public Health, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Marzilli
Lisa
L
Greenlee
Brian M
BM
Chen
Edward S
ES
Silver
Richard F
RF
Askin
Frederic B
FB
Teirstein
Alvin S
AS
Zhang
Ying
Y
Cotter
Robert J
RJ
Moller
David R
DR
D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001706:Biopsy; D015153:Blotting, Western; D002374:Catalase / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004247:DNA / Q000235:genetics; D003902:Detergents / Q000494:pharmacology; D006801:Humans; D017403:In Situ Hybridization; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000276:immunology*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D012507:Sarcoidosis / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D003902:Detergents; D012336:RNA, Ribosomal, 16S; D011994:Recombinant Proteins; D004247:DNA; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis