| Autor: |
Bashford-Rogers RJM; Department of Medicine, University of Cambridge, Cambridge, UK. rbr1@well.ox.ac.uk.; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. rbr1@well.ox.ac.uk., Bergamaschi L; Department of Medicine, University of Cambridge, Cambridge, UK.; Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK., McKinney EF; Department of Medicine, University of Cambridge, Cambridge, UK.; Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK., Pombal DC; Department of Medicine, University of Cambridge, Cambridge, UK.; Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK., Mescia F; Department of Medicine, University of Cambridge, Cambridge, UK.; Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK., Lee JC; Department of Medicine, University of Cambridge, Cambridge, UK.; Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK., Thomas DC; Department of Medicine, University of Cambridge, Cambridge, UK., Flint SM; Department of Medicine, University of Cambridge, Cambridge, UK.; ImmunoInflammation Therapy Area Unit, GlaxoSmithKline, Stevenage, UK., Kellam P; Department of Medicine, Division of Infectious Diseases, Imperial College, London, UK., Jayne DRW; Department of Medicine, University of Cambridge, Cambridge, UK., Lyons PA; Department of Medicine, University of Cambridge, Cambridge, UK.; Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK., Smith KGC; Department of Medicine, University of Cambridge, Cambridge, UK. kgcs2@cam.ac.uk.; Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK. kgcs2@cam.ac.uk. |
| Abstrakt: |
B cells are important in the pathogenesis of many, and perhaps all, immune-mediated diseases. Each B cell expresses a single B cell receptor (BCR) 1 , and the diverse range of BCRs expressed by the total B cell population of an individual is termed the 'BCR repertoire'. Our understanding of the BCR repertoire in the context of immune-mediated diseases is incomplete, and defining this could provide new insights into pathogenesis and therapy. Here, we compared the BCR repertoire in systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Crohn's disease, Behçet's disease, eosinophilic granulomatosis with polyangiitis, and immunoglobulin A (IgA) vasculitis by analysing BCR clonality, use of immunoglobulin heavy-chain variable region (IGHV) genes and-in particular-isotype use. An increase in clonality in systemic lupus erythematosus and Crohn's disease that was dominated by the IgA isotype, together with skewed use of the IGHV genes in these and other diseases, suggested a microbial contribution to pathogenesis. Different immunosuppressive treatments had specific and distinct effects on the repertoire; B cells that persisted after treatment with rituximab were predominately isotype-switched and clonally expanded, whereas the inverse was true for B cells that persisted after treatment with mycophenolate mofetil. Our comparative analysis of the BCR repertoire in immune-mediated disease reveals a complex B cell architecture, providing a platform for understanding pathological mechanisms and designing treatment strategies. |
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