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Mycobacterial catalase–peroxidase is a tissue antigen and target of the adaptive immune response in systemic sarcoidosis
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2005
- Publisher :
- Rockefeller University Press, 2005.
-
Abstract
- 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.
- Subjects :
- Sarcoidosis
medicine.drug_class
Biopsy
T cell
Blotting, Western
Detergents
Immunology
Monoclonal antibody
Immune complex formation
Article
03 medical and health sciences
0302 clinical medicine
Immune system
Bacterial Proteins
Antigen
RNA, Ribosomal, 16S
medicine
Humans
Immunology and Allergy
In Situ Hybridization
030304 developmental biology
Antigens, Bacterial
0303 health sciences
biology
DNA
Mycobacterium tuberculosis
Catalase
medicine.disease
Acquired immune system
Molecular biology
Recombinant Proteins
3. Good health
medicine.anatomical_structure
030228 respiratory system
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
biology.protein
Antibody
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 201
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....186d240bfdcbf9ba98bbf12874254871
- Full Text :
- https://doi.org/10.1084/jem.20040429