anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune systemanti-proteinase 3 anti-neutrophil细胞质自身抗体概括系统性血管炎与人源化小鼠的免疫系统.pdfVIP

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anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune systemanti-proteinase 3 anti-neutrophil细胞质自身抗体概括系统性血管炎与人源化小鼠的免疫系统.pdf

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anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune systemanti-proteinase 3 anti-neutrophil细胞质自身抗体概括系统性血管炎与人源化小鼠的免疫系统

Anti-Proteinase 3 Anti-Neutrophil Cytoplasm Autoantibodies Recapitulate Systemic Vasculitis in Mice with a Humanized Immune System 1 . 2.¤ 3. 2 3,4 Mark A. Little * , Bahjat Al-Ani , Shuyu Ren , Hamad Al-Nuaimi , Maurilo Leite Jr. , Charles E. 5 2,6 3 Alpers , Caroline O. Savage , Jeremy S. Duffield * 1 Centre for Nephrology, Royal Free Hospital, University College London, London, United Kingdom, 2 Renal Institute of Birmingham, School of Infection, Immunology and Inflammation, University of Birmingham, Birmingham, United Kingdom, 3 Division of Nephrology, Department of Medicine, Center for Lung Biology and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, United States of America, 4 Division of Nephrology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 5 Department of Pathology, University of Washington, Seattle, Washington, United States of America, 6 GlaxoSmithKline UK Ltd, Uxbridge, United Kingdom Abstract Evidence is lacking for direct pathogenicity of human anti-proteinase-3 (PR3) antibodies in development of systemic vasculitis and granulomatosis with polyangiitis (GPA, Wegener’s granulomatosis). Progress in study of these antibodies in rodents has been hampered by lack of PR3 expression on murine neutrophils, and by different Fc-receptor affinities for IgG across species. Therefore, we tested whether human anti-PR3 antibodies can induce acute vasculitis in mice with a human immune system. Chimeric mice were generated by injecting human haematopoietic stem cells into irradiated NOD-scid- IL2Rc2/ 2 mice. Matched chimera mice were treated with human IgG from pa