Anti-glomerular basement membrane (anti-GBM) disease is an organ-specific autoimmune disorder characterized by autoantibodies against the glomerular and alveolar basement membranes, leading to rapidly progressive glomerulonephritis and severe alveolar hemorrhage. The noncollagenous domain of the α3 chain of type IV collagen, α3(IV)NC1, contains the main target autoantigen in this disease. Epitope mapping studies of α3(IV)NC1 have identified several nephritogenic epitopes and critical residues that bind to autoantibodies and trigger anti-GBM disease. The discovery of novel target antigens has revealed the heterogeneous nature of this disease. In addition, both epitope spreading and mimicry have been implicated in the pathogenesis of anti-GBM disease. Epitope spreading refers to the development of autoimmunity to new autoepitopes, thus worsening disease progression, whereas epitope mimicry, which occurs via sharing of critical residues with microbial peptides, can initiate autoimmunity. An understanding of these autoimmune responses may open opportunities to explore potential new therapeutic approaches for this disease. We review how current advances in epitope mapping, identification of novel autoantigens, and the phenomena of epitope spreading and mimicry have heightened the understanding of autoimmunity in the pathogenesis of anti-GBM disease, and we discuss prospects for immunotherapy.
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http://dx.doi.org/10.1053/j.ajkd.2022.07.006 | DOI Listing |
Pathology
November 2024
Department of Laboratory Immunology, PathWest Laboratory Medicine, QEII Medical Centre, Perth, WA, Australia; School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia.
Rapid testing for antineutrophil cytoplasmic antibodies (ANCAs) and glomerular basement membrane (GBM) antibodies may assist in the early diagnosis of small vessel vasculitis. Clinical utility of urgent testing of these antibodies in an Australian context is not known. Our retrospective study examined the urgent test requests for ANCA and/or GBM antibodies performed over a 2-year period.
View Article and Find Full Text PDFPharmacol Res
December 2024
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Glioblastoma (GBM) is the most common and lethal primary brain tumor. The standard treatment for newly diagnosed GBM includes surgical resection, when feasible, followed by radiotherapy and temozolomide-based chemotherapy. Upon disease progression, the anti-vascular endothelial growth factor-A (VEGF-A) monoclonal antibody bevacizumab, can be considered.
View Article and Find Full Text PDFBr J Pharmacol
December 2024
New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Background And Purpose: The current therapy cannot meet the needs of glioblastoma (GBM). V-domain immunoglobulin suppressor of T-cell activation (VISTA) is significantly up-regulated in GBM patients; however, its therapeutic potential in GBM is still unclear.
Experimental Approach: Flow cytometry was used to detect the expression of VISTA and the co-expression pattern of VISTA and programmed death receptor 1 (PD-1) on brain infiltrating lymphocytes of GBM mice.
Int J Pharm
December 2024
Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China. Electronic address:
As one of the most common brain tumors, glioblastoma (GBM) lacks efficient therapeutic treatment and remains lethal. Extracellular vesicles (EVs) have emerged as a promising platform for GBM therapies. Nevertheless, the properties of EVs are significantly influenced by their cell origins.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
November 2024
Aix-Marseille Univ, CNRS, INP, Institute of Neurophysiopathology UMR7051, Team Gliomagenesis and Microenvironment, Faculté des Sciences Médicales et Paramédicales - Secteur Timone, 27, Bd Jean Moulin, Marseille, 13005, France.
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