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Comparison of characteristics of natural autoantibodies against myeloperoxidase and anti-myeloperoxidase autoantibodies from patients with microscopic polyangiitis.

Xu, Peng-Cheng; Cui, Zhao; Cheng, Min; Hellmark, Thomas LU and Zhao, Ming (2011) In Rheumatology (Oxford, England) 50. p.1236-1243
Abstract
Objective. Natural autoantibodies (NAAs) against MPO exist in normal human plasma. In the current study, the immune characteristics of MPO-NAA and MPO-ANCA were examined and compared with the aim to investigate the pathogenesis of MPO-ANCA. Methods. MPO-NAAs were affinity purified from normal plasma of five healthy blood donors and one batch of IVIG. MPO-ANCAs were purified from plasma of 10 patients with MPA. Antigen specificity of the antibodies was tested by western blot analysis. The titre, the avidity, the Immunoglobulin G (IgG) subclasses and the effect of the antibodies towards the binding between ceruloplasmin and MPO were tested using ELISAs. The MPO-NAA-induced production of reactive oxygen species was assessed using oxidation of... (More)
Objective. Natural autoantibodies (NAAs) against MPO exist in normal human plasma. In the current study, the immune characteristics of MPO-NAA and MPO-ANCA were examined and compared with the aim to investigate the pathogenesis of MPO-ANCA. Methods. MPO-NAAs were affinity purified from normal plasma of five healthy blood donors and one batch of IVIG. MPO-ANCAs were purified from plasma of 10 patients with MPA. Antigen specificity of the antibodies was tested by western blot analysis. The titre, the avidity, the Immunoglobulin G (IgG) subclasses and the effect of the antibodies towards the binding between ceruloplasmin and MPO were tested using ELISAs. The MPO-NAA-induced production of reactive oxygen species was assessed using oxidation of dihydrorhodamine (DHR) to rhodamine. Results. MPO-NAA recognized epitope(s) in the heavy chains of MPO with conformation-dependent structure, the same as MPO-ANCA. The median titre of MPO-NAA was lower than that of MPO-ANCA (1 : 40 vs 1 : 4800, P < 0.001). The median avidity of MPO-NAA was lower than that of MPO-ANCA (2.2 × 10(7) vs 8.7 × 10(7)/M, P = 0.014). The IgG subclasses of MPO-NAA were mainly restricted to IgG1 (100%) and lack of IgG3. The inhibition effect on the binding between ceruloplasmin and MPO was lower for MPO-NAA than MPO-ANCA (P = 0.046). The MPO-NAA-induced respiratory burst of neutrophils was significantly weaker than that of MPO-ANCA (P = 0.036). Conclusion. The lower titre, lower avidity and lack of IgG3 subclass compared with MPO-ANCA may contribute to the non-pathogenic co-existence of MPO-NAA with MPO in serum. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Rheumatology (Oxford, England)
volume
50
pages
1236 - 1243
publisher
Oxford University Press
external identifiers
  • wos:000291746100011
  • pmid:21372002
  • scopus:79959415700
ISSN
1462-0332
DOI
10.1093/rheumatology/ker085
language
English
LU publication?
yes
id
484db8e1-7ef3-4a0b-b627-af25a6a73126 (old id 1884393)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21372002?dopt=Abstract
date added to LUP
2011-04-01 12:55:32
date last changed
2017-09-17 06:20:01
@article{484db8e1-7ef3-4a0b-b627-af25a6a73126,
  abstract     = {Objective. Natural autoantibodies (NAAs) against MPO exist in normal human plasma. In the current study, the immune characteristics of MPO-NAA and MPO-ANCA were examined and compared with the aim to investigate the pathogenesis of MPO-ANCA. Methods. MPO-NAAs were affinity purified from normal plasma of five healthy blood donors and one batch of IVIG. MPO-ANCAs were purified from plasma of 10 patients with MPA. Antigen specificity of the antibodies was tested by western blot analysis. The titre, the avidity, the Immunoglobulin G (IgG) subclasses and the effect of the antibodies towards the binding between ceruloplasmin and MPO were tested using ELISAs. The MPO-NAA-induced production of reactive oxygen species was assessed using oxidation of dihydrorhodamine (DHR) to rhodamine. Results. MPO-NAA recognized epitope(s) in the heavy chains of MPO with conformation-dependent structure, the same as MPO-ANCA. The median titre of MPO-NAA was lower than that of MPO-ANCA (1 : 40 vs 1 : 4800, P &lt; 0.001). The median avidity of MPO-NAA was lower than that of MPO-ANCA (2.2 × 10(7) vs 8.7 × 10(7)/M, P = 0.014). The IgG subclasses of MPO-NAA were mainly restricted to IgG1 (100%) and lack of IgG3. The inhibition effect on the binding between ceruloplasmin and MPO was lower for MPO-NAA than MPO-ANCA (P = 0.046). The MPO-NAA-induced respiratory burst of neutrophils was significantly weaker than that of MPO-ANCA (P = 0.036). Conclusion. The lower titre, lower avidity and lack of IgG3 subclass compared with MPO-ANCA may contribute to the non-pathogenic co-existence of MPO-NAA with MPO in serum.},
  author       = {Xu, Peng-Cheng and Cui, Zhao and Cheng, Min and Hellmark, Thomas and Zhao, Ming},
  issn         = {1462-0332},
  language     = {eng},
  pages        = {1236--1243},
  publisher    = {Oxford University Press},
  series       = {Rheumatology (Oxford, England)},
  title        = {Comparison of characteristics of natural autoantibodies against myeloperoxidase and anti-myeloperoxidase autoantibodies from patients with microscopic polyangiitis.},
  url          = {http://dx.doi.org/10.1093/rheumatology/ker085},
  volume       = {50},
  year         = {2011},
}