Mycobacterial catalase-peroxidase is a tissue antigen and target of the adaptive immune response in systemic sarcoidosis

Zhimin Song, Lisa Marzilli, Brian M. Greenlee, Edward Chen, Richard F. Silver, Frederic B Askin, Alvin S. Teirstein, Ying Zhang, Robert J. Cotter, David Moller

Research output: Contribution to journalArticle

Abstract

Sarcoidosis is a disease of unknown etiology characterized by noncaseating epithelioid granulomes, 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 (140/0) 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.

Original languageEnglish (US)
Pages (from-to)755-767
Number of pages13
JournalJournal of Experimental Medicine
Volume201
Issue number5
DOIs
StatePublished - Mar 7 2005

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Adaptive Immunity
Sarcoidosis
Catalase
Peroxidase
Antigens
Immunoglobulin G
Inflammation
Proteins
Tissue Extracts
Antigen-Antibody Complex
Granuloma
Serum
Mycobacterium tuberculosis
Immunoblotting
Detergents
Proteomics
Digestion
Mass Spectrometry
Lasers
Peptide Hydrolases

ASJC Scopus subject areas

  • Immunology

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Mycobacterial catalase-peroxidase is a tissue antigen and target of the adaptive immune response in systemic sarcoidosis. / Song, Zhimin; Marzilli, Lisa; Greenlee, Brian M.; Chen, Edward; Silver, Richard F.; Askin, Frederic B; Teirstein, Alvin S.; Zhang, Ying; Cotter, Robert J.; Moller, David.

In: Journal of Experimental Medicine, Vol. 201, No. 5, 07.03.2005, p. 755-767.

Research output: Contribution to journalArticle

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