Autoantibody-dependent amplification of inflammation in SLE
| Autor: | Beata Wojciak-Stothard, Marieta M. Ruseva, Xiao-Ning Xu, Peter Kelleher, Matthew C. Pickering, Juthathip Mongkolsapaya, Gavin R. Screaton, H. Terence Cook, Hantao Lou |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
medicine.drug_class Immunology Lupus nephritis Autoimmunity Inflammation 0601 Biochemistry and Cell Biology Monoclonal antibody Transfection Article 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Immune system medicine Animals Humans Lupus Erythematosus Systemic 1112 Oncology and Carcinogenesis lcsh:QH573-671 skin and connective tissue diseases 030304 developmental biology Autoantibodies 0303 health sciences biology Cell Death lcsh:Cytology Chemistry Autoantibody Cell Biology Neutrophil extracellular traps medicine.disease 3. Good health Disease Models Animal biology.protein Antibody medicine.symptom 030215 immunology |
| Zdroj: | Cell Death and Disease, Vol 11, Iss 9, Pp 1-15 (2020) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Anti-double stranded DNA antibodies (anti-dsDNA) are a hallmark of SLE but their role in disease pathogenesis is not fully resolved. Anti-dsDNA in serum are highly heterogeneous therefore in this study, we aimed to dissect the functional specificities of anti-dsDNA using a panel of human monoclonal antibodies (humAbs) generated from patients with active lupus nephritis. A total of 46 ANA reactive humAbs were isolated and divided into four broad classes based on their reactivity to histones, DNA and Crithidia. Functional analysis indicated that one subclass of antibodies bound strongly to decondensed DNA areas in neutrophil extracellular traps (NETs) and protected NETs from nuclease digestion, similar to the sera from active SLE patients. In addition, these anti-dsDNA antibodies could stimulate type I interferon responses in mononuclear phagocytic cells, or NF-kB activity in endothelial cells, by uptake of NETs-anti-NETs immune complexes and subsequently trigging inflammatory responses in an Fc-gamma receptor (Fcg-R)-dependant manner. Together our data suggest that only a subset of anti-dsDNA antibodies is capable to amplify inflammatory responses by deposit in the nephritic kidney in vivo, protecting NETs digestion as well as uptake of NETs immune complexes into Fcg-R-expressing cells in vitro. |
| Databáze: | OpenAIRE |
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