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Natural autoantibodies to myeloperoxidase, proteinase 3, and the glomerular basement membrane are present in normal individuals

Cui, Zhao; Zhao, Ming-hui; Segelmark, Mårten LU and Hellmark, Thomas LU (2010) In Kidney International 78(6). p.590-597
Abstract
Anti-neutrophil cytoplasmic antibodies (ANCAs) have a pathogenic role in ANCA-associated vasculitis. The origin of ANCAs and anti-glomerular basement membrane (GBM) antibodies, however, is unknown. In this study, we determined whether natural autoantibodies against myeloperoxidase (MPO), proteinase 3 (PR3), and GBM were present in each of 10 healthy Chinese and Swedish individuals, negative for all three antigens by routine ELISA. Antibodies were purified from isolated IgG by antigen-specific affinity columns. Natural anti-GBM autoantibodies gave a linear staining pattern along the GBM of human renal sections. On ethanol-fixed granulocytes, both natural anti-MPO and anti-PR3 autoantibodies gave cytoplasmic staining. The titers of natural... (More)
Anti-neutrophil cytoplasmic antibodies (ANCAs) have a pathogenic role in ANCA-associated vasculitis. The origin of ANCAs and anti-glomerular basement membrane (GBM) antibodies, however, is unknown. In this study, we determined whether natural autoantibodies against myeloperoxidase (MPO), proteinase 3 (PR3), and GBM were present in each of 10 healthy Chinese and Swedish individuals, negative for all three antigens by routine ELISA. Antibodies were purified from isolated IgG by antigen-specific affinity columns. Natural anti-GBM autoantibodies gave a linear staining pattern along the GBM of human renal sections. On ethanol-fixed granulocytes, both natural anti-MPO and anti-PR3 autoantibodies gave cytoplasmic staining. The titers of natural anti-MPO/PR3 autoantibodies were significantly lower than those from patients with vasculitis. In competition ELISA, the binding of natural anti-MPO autoantibodies could be inhibited by MPO, but not by PR3 or noncollagenous domains from type IV collagen. The same specificity results were found for natural anti-PR3 and anti-GBM autoantibodies. Overall, individuals of the Chinese origin had more natural autoantibodies than did those of the Swedish origin, but no other differences were found. Hence, our study shows that healthy individuals have masked circulating, noncross-reactive, antigen-specific natural autoantibodies against MPO, PR3, and GBM in their serum and IgG fractions. Further studies are needed to determine their role if any in the etiology of ANCA-associated vasculitis and anti-GBM disease. Kidney International (2010) 78, 590-597; doi:10.1038/ki.2010.198; published online 30 June 2010 (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
natural autoantibodies, Goodpasture's disease, myeloperoxidase, vasculitis, proteinase 3
in
Kidney International
volume
78
issue
6
pages
590 - 597
publisher
Nature Publishing Group
external identifiers
  • wos:000281467100011
  • scopus:77956230395
ISSN
1523-1755
DOI
10.1038/ki.2010.198
language
English
LU publication?
yes
id
6a9d8918-3fd3-43e3-9891-70a0c47e89b2 (old id 1672337)
date added to LUP
2010-09-23 14:31:25
date last changed
2018-07-08 03:39:56
@article{6a9d8918-3fd3-43e3-9891-70a0c47e89b2,
  abstract     = {Anti-neutrophil cytoplasmic antibodies (ANCAs) have a pathogenic role in ANCA-associated vasculitis. The origin of ANCAs and anti-glomerular basement membrane (GBM) antibodies, however, is unknown. In this study, we determined whether natural autoantibodies against myeloperoxidase (MPO), proteinase 3 (PR3), and GBM were present in each of 10 healthy Chinese and Swedish individuals, negative for all three antigens by routine ELISA. Antibodies were purified from isolated IgG by antigen-specific affinity columns. Natural anti-GBM autoantibodies gave a linear staining pattern along the GBM of human renal sections. On ethanol-fixed granulocytes, both natural anti-MPO and anti-PR3 autoantibodies gave cytoplasmic staining. The titers of natural anti-MPO/PR3 autoantibodies were significantly lower than those from patients with vasculitis. In competition ELISA, the binding of natural anti-MPO autoantibodies could be inhibited by MPO, but not by PR3 or noncollagenous domains from type IV collagen. The same specificity results were found for natural anti-PR3 and anti-GBM autoantibodies. Overall, individuals of the Chinese origin had more natural autoantibodies than did those of the Swedish origin, but no other differences were found. Hence, our study shows that healthy individuals have masked circulating, noncross-reactive, antigen-specific natural autoantibodies against MPO, PR3, and GBM in their serum and IgG fractions. Further studies are needed to determine their role if any in the etiology of ANCA-associated vasculitis and anti-GBM disease. Kidney International (2010) 78, 590-597; doi:10.1038/ki.2010.198; published online 30 June 2010},
  author       = {Cui, Zhao and Zhao, Ming-hui and Segelmark, Mårten and Hellmark, Thomas},
  issn         = {1523-1755},
  keyword      = {natural autoantibodies,Goodpasture's disease,myeloperoxidase,vasculitis,proteinase 3},
  language     = {eng},
  number       = {6},
  pages        = {590--597},
  publisher    = {Nature Publishing Group},
  series       = {Kidney International},
  title        = {Natural autoantibodies to myeloperoxidase, proteinase 3, and the glomerular basement membrane are present in normal individuals},
  url          = {http://dx.doi.org/10.1038/ki.2010.198},
  volume       = {78},
  year         = {2010},
}