Advanced

Some patients with anti-myeloperoxidase autoantibodies have a C-ANCA pattern

Segelmark, M. LU ; Baslund, B. and Wieslander, J. LU (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)
Please use this url to cite or link to this publication:
author
; and
organization
publishing date
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
  • pmid:7516271
  • scopus:0028234050
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
2021-01-31 06:45:38
@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},
  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},
}