| 1. |
- Field, Christopher B., et al.
(författare)
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Summary for Policymakers
- 2014
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Ingår i: Climate Change 2014: Impacts, Adaptation, and Vulnerability. Part A: Global and SectoralAspects.. - 9781107415379 ; , s. 1-32
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Bokkapitel (refereegranskat)
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| 2. |
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| 3. |
- Olaru, Florina, et al.
(författare)
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Proteolysis Breaks Tolerance toward Intact alpha 345(IV) Collagen, Eliciting Novel Anti-Glomerular Basement Membrane Autoantibodies Specific for alpha 345NC1 Hexamers
- 2013
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 190:4, s. 1424-1432
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Tidskriftsartikel (refereegranskat)abstract
- Goodpasture disease is an autoimmune kidney disease mediated by autoantibodies against noncollagenous domain 1 (NC1) monomers of alpha 3(IV) collagen that bind to the glomerular basement membrane (GBM), usually causing rapidly progressive glomerulonephritis (GN). We identified a novel type of human IgG4-restricted anti-GBM autoantibodies associated with mild nonprogressive GN, which specifically targeted alpha 345NC1 hexamers but not alpha 3NC1 monomers. The mechanisms eliciting these anti-GBM autoantibodies were investigated in mouse models recapitulating this phenotype. Wild-type and Fc gamma RIIB-/- mice immunized with autologous murine GBM NC1 hexamers produced mouse IgG1-restricted autoantibodies specific for alpha 345NC1 hexamers, which bound to the GBM in vivo but did not cause GN. In these mice, intact collagen IV from murine GBM was not immunogenic. However, in Col4a3(-/-) Alport mice, both intact collagen IV and NC1 hexamers from murine GBM elicited IgG Abs specific for alpha 345NC1 hexamers, which were not subclass restricted. As heterologous Ag in COL4A3-humanized mice, murine GBM NC1 hexamers elicited mouse IgG1, IgG2a, and IgG2b autoantibodies specific for alpha 345NC1 hexamers and induced anti-GBM Ab GN. These findings indicate that tolerance toward autologous intact alpha 345(IV) collagen is established in hosts expressing this Ag, even though autoreactive B cells specific for alpha 345NC1 hexamers are not purged from their repertoire. Proteolysis selectively breaches this tolerance by generating autoimmunogenic alpha 345NC1 hexamers. This provides a mechanism eliciting autoantibodies specific for alpha 345NC1 hexamers, which are restricted to noninflammatory IgG subclasses and are nonnephritogenic. In Alport syndrome, lack of tolerance toward alpha 345(IV) collagen promotes production of alloantibodies to alpha 345NC1 hexamers, including proinflammatory IgG subclasses that mediate posttransplant anti-GBM nephritis.
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| 4. |
- Pedchenko, Vadim, et al.
(författare)
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Molecular Architecture of the Goodpasture Autoantigen in Anti-GBM Nephritis
- 2010
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 363:4, s. 343-354
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND In Goodpasture's disease, circulating autoantibodies bind to the noncollagenous-1 (NC1) domain of type IV collagen in the glomerular basement membrane (GBM). The specificity and molecular architecture of epitopes of tissue-bound autoantibodies are unknown. Alport's post-transplantation nephritis, which is mediated by allo-antibodies against the GBM, occurs after kidney transplantation in some patients with Alport's syndrome. We compared the conformations of the antibody epitopes in Goodpasture's disease and Alport's post-transplantation nephritis with the intention of finding clues to the pathogenesis of anti-GBM glomerulonephritis. METHODS We used an enzyme-linked immunosorbent assay to determine the specificity of circulating autoantibodies and kidney-bound antibodies to NC1 domains. Circulating antibodies were analyzed in 57 patients with Goodpasture's disease, and kidney-bound antibodies were analyzed in 14 patients with Goodpasture's disease and 2 patients with Alport's post-transplantation nephritis. The molecular architecture of key epitope regions was deduced with the use of chimeric molecules and a three-dimensional model of the alpha 345NC1 hexamer. RESULTS In patients with Goodpasture's disease, both autoantibodies to the alpha 3NC1 monomer and antibodies to the alpha 5NC1 monomer (and fewer to the alpha 4NC1 monomer) were bound in the kidneys and lungs, indicating roles for the alpha 3NC1 and alpha 5NC1 monomers as autoantigens. High antibody titers at diagnosis of anti-GBM disease were associated with ultimate loss of renal function. The antibodies bound to distinct epitopes encompassing region Ea in the alpha 5NC1 monomer and regions E-A and Eb in the alpha 3NC1 monomer, but they did not bind to the native cross-linked alpha 345NC1 hexamer. In contrast, in patients with Alport's post-transplantation nephritis, allo-antibodies bound to the E-A region of the alpha 5NC1 subunit in the intact hexamer, and binding decreased on dissociation. CONCLUSIONS The development of Goodpasture's disease may be considered an autoimmune "conformeropathy" that involves perturbation of the quaternary structure of the alpha 345NC1 hexamer, inducing a pathogenic conformational change in the alpha 3NC1 and alpha 5NC1 subunits, which in turn elicits an autoimmune response.
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| 5. |
- Rajaei, Hossein, et al.
(författare)
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Catalogue of the lepidoptera of Iran
- 2023
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Ingår i: Integrative Systematics. - : Stuttgart State Museum of Natural History. - 2628-2380. ; 6:SP1, s. 121-459
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Tidskriftsartikel (refereegranskat)
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