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Your search keyword '"Pappworth, Isabel Y."' showing total 10 results
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10 results on '"Pappworth, Isabel Y."'

3. Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice

Author

Smith-Jackson, Kate, Yang, Yi, Denton, Harriet, Pappworth, Isabel Y., Cooke, Katie, Barlow, Paul N., Atkinson, John P., Liszewski, M. Kathryn, Pickering, Matthew C., Kavanagh, David, Cook, H. Terence, and Marchbank, Kevin J.

Subjects
Care and treatment, Research, Genetic aspects, Complement system proteins -- Research, Hemolytic-uremic syndrome -- Genetic aspects -- Care and treatment -- Research, Promoters (Genetics) -- Research, Complement (Immunology) -- Research
Abstract

Introduction Our understanding and treatment of complement-mediated diseases has grown exponentially over the last 20 years. We now understand that complement plays an integral role in many autoimmune-and inflammation-based diseases [...], Atypical hemolytic uremic syndrome (aHUS) is frequently associated in humans with loss-of-function mutations in complement-regulating proteins or gain-of-function mutations in complement- activating proteins. Thus, aHUS provides an archetypal complement-mediated disease with which to model new therapeutic strategies and treatments. Herein, we show that, when transferred to mice, an aHUS-associated gain-of-function change (D1115N) to the complementactivation protein C3 results in aHUS. Homozygous C3 p.D1115N (C3KI) mice developed spontaneous chronic thrombotic microangiopathy together with hematuria, thrombocytopenia, elevated creatinine, and evidence of hemolysis. Mice with active disease had reduced plasma C3 with C3 fragment and C9 deposition within the kidney. Therapeutic blockade or genetic deletion of C5, a protein downstream of C3 in the complement cascade, protected homozygous C3KI mice from thrombotic microangiopathy and aHUS. Thus, our data provide in vivo modeling evidence that gain-of-function changes in complement C3 drive aHUS. They also show that long-term C5 deficiency is not accompanied by development of other renal complications (such as C3 glomerulopathy) despite sustained dysregulation of C3. Our results suggest that this preclinical model will allow testing of novel complement inhibitors with the aim of developing precisely targeted therapeutics that could have application in many complement-mediated diseases.

Published
2019
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4. Selectivity of C3-opsonin targeted complement inhibitors: A distinct advantage in the protection of erythrocytes from paroxysmal nocturnal hemoglobinuria patients

Author

Schmidt, Christoph Q., Harder, Markus J., Nichols, Eva-Maria, Hebecker, Mario, Anliker, Markus, Höchsmann, Britta, Simmet, Thomas, Csincsi, Ádám I., Uzonyi, Barbara, Pappworth, Isabel Y., Ricklin, Daniel, Lambris, John D., Schrezenmeier, Hubert, Józsi, Mihály, and Marchbank, Kevin J.

Published
2016
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7. Homodimeric Minimal Factor H: In Vivo Tracking and Extended Dosing Studies in Factor H Deficient Mice

Author

Kamala, Ola, primary, Malik, Talat H., additional, Hallam, Thomas M., additional, Cox, Thomas E., additional, Yang, Yi, additional, Vyas, Falguni, additional, Luli, Saimir, additional, Connelly, Chloe, additional, Gibson, Beth, additional, Smith-Jackson, Kate, additional, Denton, Harriet, additional, Pappworth, Isabel Y., additional, Huang, Lei, additional, Kavanagh, David, additional, Pickering, Matthew C., additional, and Marchbank, Kevin J., additional

Published
2021
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8. C3 Glomerulopathy and Related Disorders in Children

Author

Wong, Edwin K.S., primary, Marchbank, Kevin J., additional, Lomax-Browne, Hannah, additional, Pappworth, Isabel Y., additional, Denton, Harriet, additional, Cooke, Katie, additional, Ward, Sophie, additional, McLoughlin, Amy-Claire, additional, Richardson, Grant, additional, Wilson, Valerie, additional, Harris, Claire L., additional, Morgan, B. Paul, additional, Hakobyan, Svetlana, additional, McAlinden, Paul, additional, Gale, Daniel P., additional, Maxwell, Heather, additional, Christian, Martin, additional, Malcomson, Roger, additional, Goodship, Timothy H.J., additional, Marks, Stephen D., additional, Pickering, Matthew C., additional, Kavanagh, David, additional, Cook, H. Terence, additional, and Johnson, Sally A., additional

Published
2021
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9. Murine Factor H Co-Produced in Yeast With Protein Disulfide Isomerase Ameliorated C3 Dysregulation in Factor H-Deficient Mice

Author

Kerr, Heather, primary, Herbert, Andrew P., additional, Makou, Elisavet, additional, Abramczyk, Dariusz, additional, Malik, Talat H., additional, Lomax-Browne, Hannah, additional, Yang, Yi, additional, Pappworth, Isabel Y., additional, Denton, Harriet, additional, Richards, Anna, additional, Marchbank, Kevin J., additional, Pickering, Matthew C., additional, and Barlow, Paul N., additional

Published
2021
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