Molecular Analysis of Goodpasture’s Disease Following Hematopoietic Stem Cell Transplant in a Pediatric Patient, Recalls the Conformeropathy of Wild-Type Anti-GBM Disease
| العنوان: | Molecular Analysis of Goodpasture’s Disease Following Hematopoietic Stem Cell Transplant in a Pediatric Patient, Recalls the Conformeropathy of Wild-Type Anti-GBM Disease |
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| المؤلفون: | Paul E. Gray, Hugh McCarthy, Owen M. Siggs, Moin A. Saleem, Tracy O' Brien, Katie Frith, John B. Ziegler, A. Richard Kitching, Agnes B. Fogo, Billy G. Hudson, Vadim Pedchenko |
| المصدر: | Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology Gray, P E, McCarthy, H, Siggs, O M, Saleem, M A, O' Brien, T, Frith, K, Ziegler, J B, Kitching, A R, Fogo, A B, Hudson, B G & Pedchenko, V 2019, ' Molecular Analysis of Goodpasture's Disease Following Hematopoietic Stem Cell Transplant in a Pediatric Patient, Recalls the Conformeropathy of Wild-Type Anti-GBM Disease ', Frontiers in Immunology, vol. 10, 2659 . https://doi.org/10.3389/fimmu.2019.02659Test |
| بيانات النشر: | Frontiers Media S.A., 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Collagen Type IV, Male, lcsh:Immunologic diseases. Allergy, Anti-Glomerular Basement Membrane Disease, Immunology, conformeropathy, Random hexamer, medicine.disease_cause, Autoantigens, Epitope, Autoimmunity, anti-GBM, alloimmunity, Epitopes, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Isoantibodies, medicine, Humans, Immunology and Allergy, Rapidly progressive glomerulonephritis, Child, Original Research, Autoantibodies, 030304 developmental biology, Basement membrane, GvHD, 0303 health sciences, biology, Chemistry, autoimmunity, Hematopoietic Stem Cell Transplantation, Autoantibody, Goodpastures, Allografts, medicine.disease, Molecular biology, Lymphoproliferative Disorders, 3. Good health, medicine.anatomical_structure, glomerular basement membrane, 030220 oncology & carcinogenesis, biology.protein, Stem cell, Antibody, lcsh:RC581-607 |
| الوصف: | Background: Goodpasture's disease (GP) is mediated by autoantibodies that bind the glomerular and alveolar basement membrane, causing rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. The autoantibodies bind neoepitopes formed upon disruption of the quaternary structure of α345NC1 hexamer, a critical structural domain of α345 collagen IV scaffolds. Hexamer disruption leads to a conformational changes that transitions α3 and α5NC1 subunits into immunogens, however, the trigger remains unknown. This contrasts with another anti-GBM disease, Alports' post-transplant nephritis (APTN), where the pathogenic alloantibody binds directly to native NC1 hexamer. The current report includes the first study of antigenic specificity and allo-incompatability in anti-GBM disease occurring after allogeneic haematopoietic stem cell transplant (HSCT). Results: The anti-GBM antibodies were found to be directed predominantly against the EA epitope of the α3 NC1 monomer of collagen IV and developed rapidly in patient serum reaching peak level within 5 weeks. Autoantibody binding to native α345NC1 hexamer was minimal; however, binding was greatly increased upon dissociation of the native hexamer. There were no polymorphic genetic differences between donor and recipient collagen IV genes which would be predicted to cause a significant NC1 conformational change or to provide a target for antibody binding. Both patient and donor possessed the Goodpasture's susceptibility HLA-allele DRB1*1501. Conclusions: The current report includes the first in-depth study of allo-incompatability and antigenic specificity in anti-GBM disease occurring after allogeneic haematopoietic stem cell transplant (HSCT). No polymorphic genetic differences were identified between donor and recipient collagen IV genes which would be predicted to provide a target for antibody binding. Furthermore, autoantibody binding to native α345NC1 hexamer was minimal, increasing greatly upon dissociation of the native hexamer, resembling wild-type GP diseases and marking this as the first example of a post-HSCT conformeropathy. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b6b806efa2ce812af82b7d8995cec32Test https://www.frontiersin.org/article/10.3389/fimmu.2019.02659/fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4b6b806efa2ce812af82b7d8995cec32 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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