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J. Biol. Chem., Vol. 275, Issue 40, 30844-30848, October 6, 2000
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From the Goodpasture disease fulfils all criteria for a
classical autoimmune disease, where autoantibodies targeted against the
non-collagenous domain of the
Molecular Properties of the Goodpasture Epitope*
,, and Department of Nephrology, Lund University
Hospital, S-22185 Lund, Sweden and § Wieslab AB, S-22370
Lund, Sweden
3-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
1-chain by exchanging nine residues to the corresponding ones of
3. 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
3-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.
*
This work was supported by Swedish Medical Research Council
Grant 16X-09487, the Lundberg Foundation, the Greta och Johan Koch's Foundation, the Tegger's Foundation, and by a grant from the
"Network for Inflammation Research" funded by the Swedish Foundation for Strategic Research.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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