Molecular properties of the Goodpasture epitope
Gunnarsson, Andreas ; Hellmark, Thomas LU
and Wieslander, Jörgen
LU
(2000)
In Journal of Biological Chemistry
275(40).
p.30844-30848
- Abstract
- Goodpasture disease fulfils all criteria for a classical autoimmune disease, where autoantibodies targeted against the non-collagenous domain of the alpha3-chain of collagen IV initiates an inflammatory destruction of the basement membrane in kidney glomeruli and lung alveoli. This leads to a rapidly progressive glomerulonephritis and severe pulmonary hemorrhage. Previous studies have indicated a limited epitope for the toxic antibodies in the N-terminal part of the non-collagenous domain. The epitope has been partially characterized by recreating the epitope in the non-reactive alpha1-chain by exchanging nine residues to the corresponding ones of alpha3. In this study we have investigated to what extent each of these amino acids... (More)
- Goodpasture disease fulfils all criteria for a classical autoimmune disease, where autoantibodies targeted against the non-collagenous domain of the alpha3-chain of collagen IV initiates an inflammatory destruction of the basement membrane in kidney glomeruli and lung alveoli. This leads to a rapidly progressive glomerulonephritis and severe pulmonary hemorrhage. Previous studies have indicated a limited epitope for the toxic antibodies in the N-terminal part of the non-collagenous domain. The epitope has been partially characterized by recreating the epitope in the non-reactive alpha1-chain by exchanging nine residues to the corresponding ones of alpha3. In this study we have investigated to what extent each of these amino acids contribute to the antibody binding in different patient sera. The results show that seven of the nine substitutions are enough to get an epitope that is recognized equally well as the native alpha3-chain by all sera from 20 clinically verified Goodpasture patients. Furthermore, the patient sera reactivity against the different recombinant chains used in the study are very similar, with some minor exceptions, strongly supporting a highly defined and restricted epitope. We are convinced that the restriction of the epitope is of significant importance for the understanding of the etiology of the disease. Thereby also making every step on the way to characterization of the epitope a crucial step on the way to specific therapy for the disease. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1116535
- author
- Gunnarsson, Andreas
; Hellmark, Thomas
LU
and Wieslander, Jörgen
LU
- organization
- publishing date
- 2000
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 275
- issue
- 40
- pages
- 30844 - 30848
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:10896942
- scopus:0034613171
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M004717200
- language
- English
- LU publication?
- yes
- id
- 3156d49f-f26a-445b-90d3-4e70f1ec64a2 (old id 1116535)
- date added to LUP
- 2016-04-01 11:42:46
- date last changed
- 2022-02-18 03:45:45
@article{3156d49f-f26a-445b-90d3-4e70f1ec64a2,
abstract = {{Goodpasture disease fulfils all criteria for a classical autoimmune disease, where autoantibodies targeted against the non-collagenous domain of the alpha3-chain of collagen IV initiates an inflammatory destruction of the basement membrane in kidney glomeruli and lung alveoli. This leads to a rapidly progressive glomerulonephritis and severe pulmonary hemorrhage. Previous studies have indicated a limited epitope for the toxic antibodies in the N-terminal part of the non-collagenous domain. The epitope has been partially characterized by recreating the epitope in the non-reactive alpha1-chain by exchanging nine residues to the corresponding ones of alpha3. In this study we have investigated to what extent each of these amino acids contribute to the antibody binding in different patient sera. The results show that seven of the nine substitutions are enough to get an epitope that is recognized equally well as the native alpha3-chain by all sera from 20 clinically verified Goodpasture patients. Furthermore, the patient sera reactivity against the different recombinant chains used in the study are very similar, with some minor exceptions, strongly supporting a highly defined and restricted epitope. We are convinced that the restriction of the epitope is of significant importance for the understanding of the etiology of the disease. Thereby also making every step on the way to characterization of the epitope a crucial step on the way to specific therapy for the disease.}},
author = {{Gunnarsson, Andreas and Hellmark, Thomas and Wieslander, Jörgen}},
issn = {{1083-351X}},
language = {{eng}},
number = {{40}},
pages = {{30844--30848}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Molecular properties of the Goodpasture epitope}},
url = {{http://dx.doi.org/10.1074/jbc.M004717200}},
doi = {{10.1074/jbc.M004717200}},
volume = {{275}},
year = {{2000}},
}