Some patients with anti-myeloperoxidase autoantibodies have a C-ANCA pattern
(1994) In Clinical and Experimental Immunology 96(3). p.458-465- Abstract
Rapidly progressive glomerulonephritis with or without other signs of systemic vasculitis is often accompanied by antibodies to myeloperoxidase. Such antibodies normally produce a perinuclear pattern on ethanol-fixed neutrophils (perinuclear anti-neutrophil cytoplasm antibodies (P-ANCA)) at indirect immunofluorescence. We report here sera from three patients that are anti-myeloperoxidase-positive in ELISA that instead produce a cytoplasmic pattern (classical anti-neutrophil cytoplasmic antibodies (C-ANCA)), a pattern normally seen in conjunction with antibodies to proteinase 3. These sera did not react with proteinase 3. For two of the sera the specificity of the anti-myeloperoxidase reaction was confirmed with inhibition-ELISA... (More)
Rapidly progressive glomerulonephritis with or without other signs of systemic vasculitis is often accompanied by antibodies to myeloperoxidase. Such antibodies normally produce a perinuclear pattern on ethanol-fixed neutrophils (perinuclear anti-neutrophil cytoplasm antibodies (P-ANCA)) at indirect immunofluorescence. We report here sera from three patients that are anti-myeloperoxidase-positive in ELISA that instead produce a cytoplasmic pattern (classical anti-neutrophil cytoplasmic antibodies (C-ANCA)), a pattern normally seen in conjunction with antibodies to proteinase 3. These sera did not react with proteinase 3. For two of the sera the specificity of the anti-myeloperoxidase reaction was confirmed with inhibition-ELISA experiments and with immunoblotting. A mouse anti-myeloperoxidase MoAb that produces a cytoplasmic pattern is also described. Competition ELISA experiments show that this antibody and anti-myeloperoxidase sera with cytoplasmic pattern recognize epitopes that are separate from epitopes recognized by another perinuclear pattern producing anti-myeloperoxidase MoAb. 'Cytoplasmic pattern' epitopes as well as 'perinuclear pattern' epitopes can be found on all three major myeloperoxidase isoforms, after separation by ion exchange chromatography. Affinity chromatography, using the cytoplasmic pattern producing anti-myeloperoxidase monoclonal antibody, shows that the epitope recognized by this MoAb is present on all myeloperoxidase molecules. This epitope is not confined to any special subpopulation. These findings indicate that all myeloperoxidase do not relocate after ethanol fixation, and that C-ANCA and P-ANCA epitopes exist simultaneously on the same myeloperoxidase molecule. We propose that the two immunofluorescence patterns arise due to different availabilities of the epitopes in the microenvironment where myeloperoxidase is present.
(Less)
- author
- Segelmark, M. LU ; Baslund, B. and Wieslander, J. LU
- organization
- publishing date
- 1994
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- ANCA, autoantibodies, glomerulonephritis, light chain disease, myeloperoxidase, systemic vasculitis
- in
- Clinical and Experimental Immunology
- volume
- 96
- issue
- 3
- pages
- 458 - 465
- publisher
- British Society for Immunology
- external identifiers
-
- scopus:0028234050
- pmid:7516271
- ISSN
- 0009-9104
- DOI
- 10.1111/j.1365-2249.1994.tb06051.x
- language
- English
- LU publication?
- yes
- id
- 5e87fd88-6109-48ff-b76f-17c6614809bb
- date added to LUP
- 2020-05-19 17:05:18
- date last changed
- 2024-05-16 11:13:07
@article{5e87fd88-6109-48ff-b76f-17c6614809bb,
abstract = {{<p>Rapidly progressive glomerulonephritis with or without other signs of systemic vasculitis is often accompanied by antibodies to myeloperoxidase. Such antibodies normally produce a perinuclear pattern on ethanol-fixed neutrophils (perinuclear anti-neutrophil cytoplasm antibodies (P-ANCA)) at indirect immunofluorescence. We report here sera from three patients that are anti-myeloperoxidase-positive in ELISA that instead produce a cytoplasmic pattern (classical anti-neutrophil cytoplasmic antibodies (C-ANCA)), a pattern normally seen in conjunction with antibodies to proteinase 3. These sera did not react with proteinase 3. For two of the sera the specificity of the anti-myeloperoxidase reaction was confirmed with inhibition-ELISA experiments and with immunoblotting. A mouse anti-myeloperoxidase MoAb that produces a cytoplasmic pattern is also described. Competition ELISA experiments show that this antibody and anti-myeloperoxidase sera with cytoplasmic pattern recognize epitopes that are separate from epitopes recognized by another perinuclear pattern producing anti-myeloperoxidase MoAb. 'Cytoplasmic pattern' epitopes as well as 'perinuclear pattern' epitopes can be found on all three major myeloperoxidase isoforms, after separation by ion exchange chromatography. Affinity chromatography, using the cytoplasmic pattern producing anti-myeloperoxidase monoclonal antibody, shows that the epitope recognized by this MoAb is present on all myeloperoxidase molecules. This epitope is not confined to any special subpopulation. These findings indicate that all myeloperoxidase do not relocate after ethanol fixation, and that C-ANCA and P-ANCA epitopes exist simultaneously on the same myeloperoxidase molecule. We propose that the two immunofluorescence patterns arise due to different availabilities of the epitopes in the microenvironment where myeloperoxidase is present.</p>}},
author = {{Segelmark, M. and Baslund, B. and Wieslander, J.}},
issn = {{0009-9104}},
keywords = {{ANCA; autoantibodies; glomerulonephritis; light chain disease; myeloperoxidase; systemic vasculitis}},
language = {{eng}},
number = {{3}},
pages = {{458--465}},
publisher = {{British Society for Immunology}},
series = {{Clinical and Experimental Immunology}},
title = {{Some patients with anti-myeloperoxidase autoantibodies have a C-ANCA pattern}},
url = {{http://dx.doi.org/10.1111/j.1365-2249.1994.tb06051.x}},
doi = {{10.1111/j.1365-2249.1994.tb06051.x}},
volume = {{96}},
year = {{1994}},
}