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Patients with Goodpasture's disease have two normal COL4A3 alleles encoding the NC1 domain of the type IV collagen {alpha}3 chain.

Persson, Ulf LU ; Michael Hertz, Jens; Carlsson, Malin LU ; Hellmark, Thomas LU ; Juncker, Inger; Wieslander, Jörgen and Segelmark, Mårten LU (2004) In Nephrology Dialysis Transplantation 19(8). p.2030-2035
Abstract
Background. Goodpasture's disease (GP) is a rare but severe disease characterized by anti-glomerular basement membrane antibodies, rapidly progressive glomerulonephritis and lung haemorrhage. The autoantibodies are restricted to a narrow epitope region on the NC1 domain of the alpha3 chain of type IV collagen. GP is strongly associated with major histocompatibility complex (MHC) allele HLA DRB1-15. Recent research, however, has failed to identify a T-cell epitope with molecular characteristics that explain the relationship between the MHC class II molecule and the autoantibody generation. We hypothesized that an as yet unidentified sequence variant in exons 48-52 of the COL4A3 gene that encodes the NC1 domain of the type IV collagen alpha3... (More)
Background. Goodpasture's disease (GP) is a rare but severe disease characterized by anti-glomerular basement membrane antibodies, rapidly progressive glomerulonephritis and lung haemorrhage. The autoantibodies are restricted to a narrow epitope region on the NC1 domain of the alpha3 chain of type IV collagen. GP is strongly associated with major histocompatibility complex (MHC) allele HLA DRB1-15. Recent research, however, has failed to identify a T-cell epitope with molecular characteristics that explain the relationship between the MHC class II molecule and the autoantibody generation. We hypothesized that an as yet unidentified sequence variant in exons 48-52 of the COL4A3 gene that encodes the NC1 domain of the type IV collagen alpha3 chain could generate a new peptide sequence that, through interaction with specific MHC class II molecules, would increase the risk of developing GP. Methods. All patients previously treated for GP at the Lund and Malmo University Hospitals, who were alive at the time of the study, were asked to participate. DNA was extracted from leukocytes and subjected to genomic tissue typing and sequencing of the COL4A3 gene exons 48-52. Results. All 15 patients in the study had a nucleotide sequence in the COL4A3 gene encoding a protein identical to GenBank entry NM_000091. HLA D allele distribution was in line with previous publications, showing a strong positive association between HLA DRB1-15, HLA DQB1-6 and GP (P < 0.02). Of the 15 GP patients, 73% carried HLA DRB1-15 and 87% carried the HLA DQB1-6 antigen. Corresponding figures for the controls were 27 and 50%. Conclusion. This study effectively falsifies the hypothesis that a minor alteration in the COL4A3 gene could be a major factor in the aetiology of GP. Scandinavian GP patients have an MHC distribution similar to that which has been described previously for Anglo-Saxon patients. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
COL4A3 gene, Goodpasture's disease
in
Nephrology Dialysis Transplantation
volume
19
issue
8
pages
2030 - 2035
publisher
Oxford University Press
external identifiers
  • pmid:15199166
  • wos:000223114000014
  • scopus:4344601924
ISSN
1460-2385
DOI
10.1093/ndt/gfh355
language
English
LU publication?
yes
id
8051a463-b56a-4223-9ee7-cb67d5d8fff6 (old id 124132)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15199166&dopt=Abstract
date added to LUP
2007-06-28 14:29:48
date last changed
2017-08-27 05:26:03
@article{8051a463-b56a-4223-9ee7-cb67d5d8fff6,
  abstract     = {Background. Goodpasture's disease (GP) is a rare but severe disease characterized by anti-glomerular basement membrane antibodies, rapidly progressive glomerulonephritis and lung haemorrhage. The autoantibodies are restricted to a narrow epitope region on the NC1 domain of the alpha3 chain of type IV collagen. GP is strongly associated with major histocompatibility complex (MHC) allele HLA DRB1-15. Recent research, however, has failed to identify a T-cell epitope with molecular characteristics that explain the relationship between the MHC class II molecule and the autoantibody generation. We hypothesized that an as yet unidentified sequence variant in exons 48-52 of the COL4A3 gene that encodes the NC1 domain of the type IV collagen alpha3 chain could generate a new peptide sequence that, through interaction with specific MHC class II molecules, would increase the risk of developing GP. Methods. All patients previously treated for GP at the Lund and Malmo University Hospitals, who were alive at the time of the study, were asked to participate. DNA was extracted from leukocytes and subjected to genomic tissue typing and sequencing of the COL4A3 gene exons 48-52. Results. All 15 patients in the study had a nucleotide sequence in the COL4A3 gene encoding a protein identical to GenBank entry NM_000091. HLA D allele distribution was in line with previous publications, showing a strong positive association between HLA DRB1-15, HLA DQB1-6 and GP (P &lt; 0.02). Of the 15 GP patients, 73% carried HLA DRB1-15 and 87% carried the HLA DQB1-6 antigen. Corresponding figures for the controls were 27 and 50%. Conclusion. This study effectively falsifies the hypothesis that a minor alteration in the COL4A3 gene could be a major factor in the aetiology of GP. Scandinavian GP patients have an MHC distribution similar to that which has been described previously for Anglo-Saxon patients.},
  author       = {Persson, Ulf and Michael Hertz, Jens and Carlsson, Malin and Hellmark, Thomas and Juncker, Inger and Wieslander, Jörgen and Segelmark, Mårten},
  issn         = {1460-2385},
  keyword      = {COL4A3 gene,Goodpasture's disease},
  language     = {eng},
  number       = {8},
  pages        = {2030--2035},
  publisher    = {Oxford University Press},
  series       = {Nephrology Dialysis Transplantation},
  title        = {Patients with Goodpasture's disease have two normal COL4A3 alleles encoding the NC1 domain of the type IV collagen {alpha}3 chain.},
  url          = {http://dx.doi.org/10.1093/ndt/gfh355},
  volume       = {19},
  year         = {2004},
}