Journal Article

Patients with Goodpasture's disease have two normal <i>COL4A3</i> alleles encoding the NC1 domain of the type IV collagen α3 chain

Ulf Persson, Jens Michael Hertz, Malin Carlsson, Thomas Hellmark, Inger Juncker, Jörgen Wieslander and Mårten Segelmark

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 19, issue 8, pages 2030-2035
Published in print August 2004 | ISSN: 0931-0509
Published online June 2004 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfh355
Patients with Goodpasture's disease have two normal COL4A3 alleles encoding the NC1 domain of the type IV collagen α3 chain

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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 α3 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 α3 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 Malmö 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.

Keywords: COL4A3 gene/Goodpasture's disease

Journal Article.  3308 words. 

Subjects: Nephrology

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