Advanced

Identification of a clinically relevant immunodominant region of collagen IV in Goodpasture disease

Hellmark, Thomas LU ; Segelmark, Mårten LU ; Unger, Christine; Burkhardt, Harald; Saus, Juan and Wieslander, Jörgen LU (1999) In Kidney International 55(3). p.936-944
Abstract
BACKGROUND: The characteristic feature of Goodpasture disease is the occurrence of an autoantibody response to the noncollagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] in the alveolar and glomerular basement membrane. These antibodies are associated with the development of a rapidly progressive glomerulonephritis, with or without lung hemorrhage, whereas autoantibodies specific for the other alpha chains of the heterotrimeric type IV collagen probably do not cause disease. In this study, we have investigated whether differences in fine specificity of autoimmune recognition of the alpha3(IV)NC1 correlate with clinical outcome. METHODS: For mapping of antibody binding to type IV collagen, chimeric collagen constructs... (More)
BACKGROUND: The characteristic feature of Goodpasture disease is the occurrence of an autoantibody response to the noncollagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] in the alveolar and glomerular basement membrane. These antibodies are associated with the development of a rapidly progressive glomerulonephritis, with or without lung hemorrhage, whereas autoantibodies specific for the other alpha chains of the heterotrimeric type IV collagen probably do not cause disease. In this study, we have investigated whether differences in fine specificity of autoimmune recognition of the alpha3(IV)NC1 correlate with clinical outcome. METHODS: For mapping of antibody binding to type IV collagen, chimeric collagen constructs were generated in which parts of the alpha3(IV)NC1 domain were replaced by the corresponding sequences of homologous nonreactive alpha1(IV). The different recombinant collagen chimeras allowed the analysis of antibody specificities in 77 sera from well-documented patients. RESULTS: One construct that harbors the aminoterminal third of the alpha3(IV)NC1 was recognized by all sera, indicating that it represents the dominant target of the B-cell response in Goodpasture disease. Seventy percent of the samples recognized other parts of the molecule as well. However, only reactivity to the N-terminus of the alpha3(IV)NC1 correlated with prognosis, that is, kidney survival after six months of follow-up. CONCLUSION: The results indicate the crucial importance of antibody recognition of this particular domain for the pathogenesis of Goodpasture disease, thereby opening new avenues for the development of better diagnostic and therapeutic procedures. (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
B cell, epitope, glomerular basement membrane, autoantibody, rapidly progressive glomerulonephritis
in
Kidney International
volume
55
issue
3
pages
936 - 944
publisher
Nature Publishing Group
external identifiers
  • pmid:10027930
  • scopus:0033050862
ISSN
1523-1755
DOI
10.1046/j.1523-1755.1999.055003936.x
language
English
LU publication?
yes
id
2e2d1829-696f-4186-8e82-a6dbe582e2af (old id 1114295)
date added to LUP
2008-07-03 16:23:22
date last changed
2017-07-23 04:38:14
@article{2e2d1829-696f-4186-8e82-a6dbe582e2af,
  abstract     = {BACKGROUND: The characteristic feature of Goodpasture disease is the occurrence of an autoantibody response to the noncollagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] in the alveolar and glomerular basement membrane. These antibodies are associated with the development of a rapidly progressive glomerulonephritis, with or without lung hemorrhage, whereas autoantibodies specific for the other alpha chains of the heterotrimeric type IV collagen probably do not cause disease. In this study, we have investigated whether differences in fine specificity of autoimmune recognition of the alpha3(IV)NC1 correlate with clinical outcome. METHODS: For mapping of antibody binding to type IV collagen, chimeric collagen constructs were generated in which parts of the alpha3(IV)NC1 domain were replaced by the corresponding sequences of homologous nonreactive alpha1(IV). The different recombinant collagen chimeras allowed the analysis of antibody specificities in 77 sera from well-documented patients. RESULTS: One construct that harbors the aminoterminal third of the alpha3(IV)NC1 was recognized by all sera, indicating that it represents the dominant target of the B-cell response in Goodpasture disease. Seventy percent of the samples recognized other parts of the molecule as well. However, only reactivity to the N-terminus of the alpha3(IV)NC1 correlated with prognosis, that is, kidney survival after six months of follow-up. CONCLUSION: The results indicate the crucial importance of antibody recognition of this particular domain for the pathogenesis of Goodpasture disease, thereby opening new avenues for the development of better diagnostic and therapeutic procedures.},
  author       = {Hellmark, Thomas and Segelmark, Mårten and Unger, Christine and Burkhardt, Harald and Saus, Juan and Wieslander, Jörgen},
  issn         = {1523-1755},
  keyword      = {B cell,epitope,glomerular basement membrane,autoantibody,rapidly progressive glomerulonephritis},
  language     = {eng},
  number       = {3},
  pages        = {936--944},
  publisher    = {Nature Publishing Group},
  series       = {Kidney International},
  title        = {Identification of a clinically relevant immunodominant region of collagen IV in Goodpasture disease},
  url          = {http://dx.doi.org/10.1046/j.1523-1755.1999.055003936.x},
  volume       = {55},
  year         = {1999},
}