Complement fragments are biomarkers of antibody-mediated endothelial injury
| Autor: | Erik Stites, Moglie Le Quintrec, Jennifer Laskowski, Brian M. Freed, Brandon Renner, Diana Jalal, James E. Cooper, Zhiying You, Joshua M. Thurman |
|---|---|
| Přispěvatelé: | University of Colorado Anschutz [Aurora], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CLINIMMUNE LABS Bioscience, Carver College of Medicine [Iowa City], University of Iowa [Iowa City] |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Graft Rejection
Male 0301 basic medicine Biopsy MESH: Allografts Kidney Antibody mediated rejection [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology MESH: Kidney Transplantation MESH: Biopsy 0302 clinical medicine MESH: Endothelial Cells Complement Activation Cells Cultured MESH: Middle Aged biology Microvesicle [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology Middle Aged Allografts 3. Good health medicine.anatomical_structure [SDV.IMM]Life Sciences [q-bio]/Immunology Female Antibody MESH: Cells Cultured Adult MESH: Complement Activation Immunology MESH: Complement System Proteins Complement MESH: Graft Rejection MESH: Vascular System Injuries Antibodies Article 03 medical and health sciences medicine MESH: Transplantation Homologous Humans Transplantation Homologous Donor specific antibody Molecular Biology Opsonin MESH: Humans business.industry MESH: Antibodies C4A Endothelial Cells MESH: Adult Complement System Proteins Biomarker MESH: Kidney Vascular System Injuries Kidney Transplantation Microvesicles In vitro MESH: Male Complement system 030104 developmental biology biology.protein MESH: Biomarkers business MESH: Female Biomarkers 030215 immunology |
| Zdroj: | Molecular Immunology Molecular Immunology, Elsevier, 2020, 118, pp.142-152. ⟨10.1016/j.molimm.2019.12.011⟩ Mol Immunol |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/j.molimm.2019.12.011⟩ |
| Popis: | International audience; Antibody-mediated rejection (AbMR) adversely affects long-term graft survival in kidney transplantation. Currently, the diagnosis of AbMR requires a kidney biopsy, and detection of complement C4d deposition in the allograft is one of the diagnostic criteria. Complement activation also generates several soluble fragments which could potentially provide non-invasive biomarkers of the process. Furthermore, microvesicles released into the plasma from injured cells can serve as biomarkers of vascular injury. To explore whether soluble complement fragments or complement fragments bound to endothelial microvesicles can be used to non-invasively detect AbMR, we developed an in vitro model in which human endothelial cells were exposed to anti-HLA antibodies and complement sufficient serum. We found that complement fragments C4a and sC5b-9 were increased in the supernatants of cells exposed to complement-sufficient serum compared to cells treated complement-deficient serum. Furthermore, complement activation on the cell surface was associated with the release of microvesicles bearing C4 and C3 fragments. We next measured these analytes in plasma from kidney transplant recipients with biopsy-proven acute AbMR (n = 9) and compared the results with those from transplant recipients who also had impaired allograft function but who did not have AbMR (n = 30). Consistent with the in vitro results, complement fragments C4a and Ba were increased in plasma from patients with AbMR compared to control subjects (P |
| Databáze: | OpenAIRE |
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