Advanced

Mapping of myeloperoxidase epitopes recognized by MPO-ANCA using human-mouse MPO chimers

Erdbrugger, U; Hellmark, Thomas LU ; Bunch, DO; Alcorta, DA; Jennette, JC; Falk, RJ and Nachman, PH (2006) In Kidney International 69(10). p.1799-1805
Abstract
Myeloperoxidase ( MPO) is one of the major target antigens of antineutrophil cytoplasmic autoantibodies ( ANCA) found in patients with small-vessel vasculitis and pauci-immune necrotizing glomerulonephritis. To date, the target epitopes of MPO-ANCA remain poorly defined. Human MPO-ANCA do not typically bind mouse MPO. We utilized the differences between human and mouse MPO to identify the target regions of MPO-ANCA. We generated five chimeric MPO molecules in which we replaced different segments of the human or mouse molecules with their homologous counterpart from the other species. Of serum samples from 28 patients screened for this study, 43 samples from 14 patients with MPO-ANCA-associated vasculitis were tested against recombinant... (More)
Myeloperoxidase ( MPO) is one of the major target antigens of antineutrophil cytoplasmic autoantibodies ( ANCA) found in patients with small-vessel vasculitis and pauci-immune necrotizing glomerulonephritis. To date, the target epitopes of MPO-ANCA remain poorly defined. Human MPO-ANCA do not typically bind mouse MPO. We utilized the differences between human and mouse MPO to identify the target regions of MPO-ANCA. We generated five chimeric MPO molecules in which we replaced different segments of the human or mouse molecules with their homologous counterpart from the other species. Of serum samples from 28 patients screened for this study, 43 samples from 14 patients with MPO-ANCA-associated vasculitis were tested against recombinant human and mouse MPO and the panel of chimeric molecules. Sera from 64 and 71% of patients bound to the carboxy-terminus of the heavy chain, in the regions of amino acids 517-667 or 668-745, respectively. No patient serum bound the MPO light chain or the amino-terminus of the heavy chain. All sera bound to only one or two regions of MPO. Although the pattern of MPO-ANCA binding changed over time ( 4-27 months) in 6 of 10 patients with several serum samples, such changes were infrequent. Other target regions of MPO-ANCA may not have been detected due to conformational differences between the native and recombinant forms of MPO. MPO-ANCA do not target a single epitope, but rather a small number of regions of MPO, primarily in the carboxy-terminus of the heavy chain. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
epitope, glomerulonephritis, myeloperoxidase, vasculitis, ANCA
in
Kidney International
volume
69
issue
10
pages
1799 - 1805
publisher
Nature Publishing Group
external identifiers
  • pmid:16557221
  • wos:000237673800023
  • scopus:33646714645
ISSN
1523-1755
DOI
10.1038/sj.ki.5000354
language
English
LU publication?
yes
id
8c98f8f5-b8dc-42d7-8074-d0d7fb402f0f (old id 408573)
date added to LUP
2007-10-02 17:29:11
date last changed
2019-03-12 02:56:09
@article{8c98f8f5-b8dc-42d7-8074-d0d7fb402f0f,
  abstract     = {Myeloperoxidase ( MPO) is one of the major target antigens of antineutrophil cytoplasmic autoantibodies ( ANCA) found in patients with small-vessel vasculitis and pauci-immune necrotizing glomerulonephritis. To date, the target epitopes of MPO-ANCA remain poorly defined. Human MPO-ANCA do not typically bind mouse MPO. We utilized the differences between human and mouse MPO to identify the target regions of MPO-ANCA. We generated five chimeric MPO molecules in which we replaced different segments of the human or mouse molecules with their homologous counterpart from the other species. Of serum samples from 28 patients screened for this study, 43 samples from 14 patients with MPO-ANCA-associated vasculitis were tested against recombinant human and mouse MPO and the panel of chimeric molecules. Sera from 64 and 71% of patients bound to the carboxy-terminus of the heavy chain, in the regions of amino acids 517-667 or 668-745, respectively. No patient serum bound the MPO light chain or the amino-terminus of the heavy chain. All sera bound to only one or two regions of MPO. Although the pattern of MPO-ANCA binding changed over time ( 4-27 months) in 6 of 10 patients with several serum samples, such changes were infrequent. Other target regions of MPO-ANCA may not have been detected due to conformational differences between the native and recombinant forms of MPO. MPO-ANCA do not target a single epitope, but rather a small number of regions of MPO, primarily in the carboxy-terminus of the heavy chain.},
  author       = {Erdbrugger, U and Hellmark, Thomas and Bunch, DO and Alcorta, DA and Jennette, JC and Falk, RJ and Nachman, PH},
  issn         = {1523-1755},
  keyword      = {epitope,glomerulonephritis,myeloperoxidase,vasculitis,ANCA},
  language     = {eng},
  number       = {10},
  pages        = {1799--1805},
  publisher    = {Nature Publishing Group},
  series       = {Kidney International},
  title        = {Mapping of myeloperoxidase epitopes recognized by MPO-ANCA using human-mouse MPO chimers},
  url          = {http://dx.doi.org/10.1038/sj.ki.5000354},
  volume       = {69},
  year         = {2006},
}