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3. The effects of plasma exchange and glucocorticoids on early kidney function among patients with ANCA-associated vasculitis in the PEXIVAS trial

Author

Paizis, Kathy, Walters, Giles, Jardine, Meg, Milton, Caroline, Ibraham, Abu, Siva, Brian, Desmond, Michael, Perkovic, Vlado, Kurtkoti, Jadadeesh, Vilayur, Eswari, Cass, Alan, Summers, Shaun, Brown, Fiona, Ryan, Jessica, Kerr, Peter, Noble, Euan, Luxton, Grant, Mudge, David W., Hawley, Carmel, Johnson, David W., Peh, Chen Au, Faull, Randall J., Ranganathan, Dwarakanathan, Jeffs, Lisa, Nicholls, Kathy, Hughes, Peter, Cooper, Bruce, Boudville, Neil, Ford, Sharon, Langham, Robyn, Reidlinger, Donna, AliciaMorrish, Badve, Sunil V., Pascoe, Elaine, Paul-Brent, Peta-Anne, Robison, Laura, Valks, Andrea, Blockmans, Daniel, Henckaerts, Liesbet, Sprangers, Ben, Suri, Rita, Brachemi, Soumeya, Clark, William, Garg, Amit, Carette, Simon, Pagnoux, Christian, Reich, Heather, Barth, David, Walsh, Michael, Khalidi, Nader, Cox, Gerry, Mazzetti, Andrea, Robins, Diane, Wald, Ron, Perl, Jeffrey, Pavenski, Katerina, Dacouris, Niki, Levin, Adeera, Copland, Michael, Fairhead, Todd, Pannu, Neesh, Qarni, Muhammad Uwais, Habib, Syed, Girard, Louis, Manns, Braden, Tesar, Vladimir, Hruskova, Zdenka, Chocova, Zdenka, Povlsen, Johan, Gregersen, Jon, Ivarsen, Per, Birn, Henrik, Krarup, Elizabeth, Pedersen, Erling B., Thomsen, Ingrid, Bech, Jesper Nørgaard, Szpirt, Wladmir, Egfjord, Martin, Mesbah, Rafik, Bataille, Pierre, Rey, Isabelle, Chantrel, François, Vanhille, Philipe, Quémeneur, Thomas, Carron, Pierre-Louis, Zaoui, Philippe, de Moreuil, Claire, Gosselin, Morgane, Delluc, Aurélien, Hanrotel-Saliou, Catherine, Le Jeune, Mathilde, Ficheux, Maxence, Aniort, Julien, Lavigne, Christian, Augusto, Jean Francois, Chauveau, Dominique, Guitard, Joëlle, Huart, Antoine, Ribes, David, Gatault, Philippe, Becmeur, Camille, Muller, Sandrine, Betz, Valérie, Klein, Alexandre, Blaison, Gilles, Seror, Raphaele, Francois, Hélène, Mariette, Xavier, Aubrun, Aurore, Coustet, Baptiste, Palazzo, Elisabeth, Ottaviani, Sébastien, Goulenok, Tiphaine, Daugas, Eric, Dieudé, Philipe, Papo, Thomas, Lebas, Céline, Lionet, Arnaud, Guillevin, Loïc, Mouthon, Luc, Puéchal, Xavier, Jourde-Chiche, Noémie, Ruivard, Marc, Karras, Alexandre, Limal, Nicolas, Kofman, Thomas, Le Quellec, Alain, Maurier, François, Gibelin, Aude, Parrot, Antoine, Bachmeyer, Claude, Gombert, Bruno, Nouvier, Mathilde, Lega, Jean-Christophe, Fain, Olivier, Andrès, Emmanuel, Cottet, Rachel, Gregorini, Gina, Jeannin, Guido, Possenti, Stefano, Buzio, Carlo, Vaglio, Augusto, Oliva, Elena, Makino, Hirofumi, Muso, Eri, Endo, Tomomi, Kakita, Hiroko, Suzuki, Hiroyuki, Handa, Takaya, Kang, Youngna, Ariyasu, Yuki, Tsukamoto, Tatsuo, Endo, Shuichiro, Miyata, Hitomi, Yamada, Hiroyuki, Ito-Ihara, Toshiko, Uchida, Shunya, Kono, Hajime, Fujigaki, Yoshihide, Kikuchi, Hirotoshi, Nanki, Toshihiro, Kato, Hideki, Okamoto, Akiko, Asako, Kurumi, Suzuki, Kazuo, Hamano, Yoshitomo, Yamagata, Kunihiro, Usui, Joichi, Fujimoto, Shouichi, Sato, Yuji, Kikuchi, Masao, Flores-Suárez, Luis Felipe, Sánchez-Guerrero, Sergio A., Collins, Michael, Schollum, John, de Zoysa, Janak, Quincy, Vicki, Sizeland, Peter, Aasarod, Knut, Solbu, Marit, Bruun, Trude Jannecke, Koldingsnes, Wenche, Wludarczyk, Anna, Nowak, Ilona, Gorka, Jacek, Sznajd, Jan, Padjas, Agnieszka, Jankowski, Milosz, Widawska, Agnieszka, Szczeklik, Wojciech, Ballarin, Jose, Bruchfeld, Annette, Efvergren, Mats, Eriksson, Per, Westman, Kerstin, Selga, Daina, Heijl, Caroline, Ohlsson, Sophie, Segelmark, Marten, Basu, Neil, Kidder, Dana, Fluck, Nicholas, Jayne, David R.W., Smith, Rona, Wilcocks, Lisa, McClure, Mark, Jones, Rachel, Trivedi, Sapna, Gopaluni, Seerapani, Brettell, Elizabeth, Crump, Paul, Feilbach, Annika, Hewitt, Catherine, Hilken, Nick, Howman, Andrew, Hughes, Terry, Ives, Natalie, Jarrett, Hugh, Mehta, Samir, Record, Rebecca, Ryan, Gemma, Sidile, Chaka, Wheatley, Keith, Sheerin, Brown, Alison, Baines, Laura Anne, Lordan, Jim, Pusey, Charles, Tanna, Anisha, McAdoo, Stephen, Levy, Jeremy, Griffith, Megan, Klebe, Bernhard, Doulton, Timothy, Warwick, Graham, Burton, James, Barratt, Jonathon, Topham, Peter, Baines, Richard, Brunskill, Nigel, Al-Jayyousi, Reem, Hamilton, Patrick, Patel, Mumtaz, Mitra, Sandip, Brown, Nina, Sharples, Edward, Luqmani, Raashid, Harper, Lorraine, Rhodes, Benjamin, Chanouzas, Dimitrios, Morgan, Matthew, Hewins, Peter, Floßmann, Oliver, Bhandary, Nitin, Foxton, Julie, Jones, Linda, King, Jenny, Smyth, Lucy, D’Souza, Richard, Haigh, Richard, Hough, Maxine, Salama, Alan, Burns, Aine, Little, Mark, Dhaun, Neeraj, Dhaygude, Ajay, Basnayake, Kolitha, Iggo, Neil, Jones, Daniel, Oliveira, David, MacPhee, Iain A.M., Dunn, Emma, Lewington, Andrew J.P., Fan, Stanley Linsun, Rajakariar, Ravindra, Yaqoob, Magdi, Short, Andrew, Geddes, Colin, Mackinnon, Bruce, Jardine, Alan G., Monach, Paul, Merkel, Peter A., Amudala, Naomi, Quillen, Karen, Weisman, Michael, Wallace, Daniel, Forbess, Lindsy, Venuturupalli, Swamy, Langford, Carol, Hajj-Ali, Rula, Koo, Anna, Hoffman, Gary, Specks, Ulrich, Keogh, Karina, Ytterberg, Steven, Winters, Jeff, Warrington, Kenneth, Cartin-Ceba, Rodrigo, Peikert, Tobias, Fervenza, Fernando, Baqir, Misbah, Nachman, Patrick, Detwiler, Randy, Mottl, Amy, Derebail, Vimal, McGregor, JulieAnne, Sreih, Antoine, Rhee, Rennie, McAlear, Carol, Aqui, Nicole, Moreland, Larry, Kiss, Joseph, Liang, Kimberly, Mohan, Niveditha, Balogun, Rasheed, Li, Tingting, Brasington, Richard, Odler, Balazs, Riedl, Regina, Geetha, Duvuru, Szpirt, Wladimir M., Uchida, Lisa, Wallace, Zachary S., Pusey, Charles D., Little, Mark A., and Kronbichler, Andreas

Published
2024
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5. TLR7 gain-of-function genetic variation causes human lupus

Author

Brown, Grant J., Cañete, Pablo F., Wang, Hao, Medhavy, Arti, Bones, Josiah, Roco, Jonathan A., He, Yuke, Qin, Yuting, Cappello, Jean, Ellyard, Julia I., Bassett, Katharine, Shen, Qian, Burgio, Gaetan, Zhang, Yaoyuan, Turnbull, Cynthia, Meng, Xiangpeng, Wu, Phil, Cho, Eun, Miosge, Lisa A., Andrews, T. Daniel, Field, Matt A., Tvorogov, Denis, Lopez, Angel F., Babon, Jeffrey J., López, Cristina Aparicio, Gónzalez-Murillo, África, Garulo, Daniel Clemente, Pascual, Virginia, Levy, Tess, Mallack, Eric J., Calame, Daniel G., Lotze, Timothy, Lupski, James R., Ding, Huihua, Ullah, Tomalika R., Walters, Giles D., Koina, Mark E., Cook, Matthew C., Shen, Nan, de Lucas Collantes, Carmen, Corry, Ben, Gantier, Michael P., Athanasopoulos, Vicki, and Vinuesa, Carola G.

Published
2022
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6. Risk of Relapse of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis in a Randomized Controlled Trial of Plasma Exchange and Glucocorticoids.

Author

Junek, Mats L., Merkel, Peter A., Vilayur, Eswari, Wald, Ron, Khalidi, Nader, Jayne, David, Walsh, Michael, Paizis, Kathy, Reidlinger, Donna, Morrish, Alicia, Badve, Sunil V, Pascoe, Elaine, Paul‐Brent, Peta‐Anne, Robison, Laura, Valks, Andrea, Walters, Giles, Jardine, Meg, Milton, Caroline, Ibraham, Abu, and Siva, Brian

Subjects
VASCULITIS treatment, AUTOIMMUNE disease treatment, RISK assessment, DATA analysis, ANTINEUTROPHIL cytoplasmic antibodies, SEVERITY of illness index, DISEASE remission, DESCRIPTIVE statistics, HEMODIALYSIS, STATISTICS, DISEASE relapse, CONFIDENCE intervals, PLASMA exchange (Therapeutics), GLUCOCORTICOIDS, CYCLOPHOSPHAMIDE, DISEASE risk factors
Abstract

Objective: Relapses of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis are important events that can cause organ dysfunction and reduce quality of life. Understanding the effects of the initial treatments for ANCA‐associated vasculitis on the subsequent risk of relapse may help guide monitoring and treatment. Methods: We performed a post hoc analysis of participants with severe ANCA‐associated vasculitis enrolled in an international two‐by‐two factorial randomized controlled trial comparing the effects of plasma exchange (PLEX) to no PLEX and a regimen of reduced glucocorticoid exposure to a standard regimen. We estimated the effects of treatments on relapses of any severity using three competing risk time‐to‐event models adjusted for patient and disease characteristics and other treatments. Each model was adjusted for disease manifestations in different ways. Results: Of 704 participants, 649 (92.2%) achieved remission and 147 (22.7%) experienced 204 relapses. The relapse rate was 10.3 (95% confidence interval [CI] 8.4–12.1) relapses per 100 patient‐years. Neither the use of PLEX (subhazard ratio 0.91–0.94; 95% CIs range from 0.66 to 1.31) nor a glucocorticoid regimen (subhazard ratio 0.93–0.94; 95% CIs range from 0.67 to 1.35) appreciably changed the risk of relapse. Proteinase 3–ANCA and the presence of nonhemorrhagic respiratory manifestations of the disease at trial entry were associated with increased risks of relapse. Receiving dialysis at baseline and administration of oral cyclophosphamide as induction therapy were associated with lower risks of relapse. Conclusion: In patients with severe ANCA‐associated vasculitis, relapses remain common; neither the use of PLEX nor an initial glucocorticoid tapering regimen impacted relapse risk. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity

Author

Zhang, Yaoyuan, primary, Morris, Rhiannon, additional, Brown, Grant J., additional, Lorenzo, Ayla May D., additional, Meng, Xiangpeng, additional, Kershaw, Nadia J., additional, Kiridena, Pamudika, additional, Burgio, Gaétan, additional, Gross, Simon, additional, Cappello, Jean Y., additional, Shen, Qian, additional, Wang, Hao, additional, Turnbull, Cynthia, additional, Lea-Henry, Tom, additional, Stanley, Maurice, additional, Yu, Zhijia, additional, Ballard, Fiona D., additional, Chuah, Aaron, additional, Lee, James C., additional, Hatch, Ann-Maree, additional, Enders, Anselm, additional, Masters, Seth L., additional, Headley, Alexander P., additional, Trnka, Peter, additional, Mallon, Dominic, additional, Fletcher, Jeffery T., additional, Walters, Giles D., additional, Šestan, Mario, additional, Jelušić, Marija, additional, Cook, Matthew C., additional, Athanasopoulos, Vicki, additional, Fulcher, David A., additional, Babon, Jeffrey J., additional, Vinuesa, Carola G., additional, and Ellyard, Julia I., additional

Published
2024
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8. Management and treatment of glomerular diseases (part 2): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Author

Adler, Sharon G., Alpers, Charles E., Ayoub, Isabelle, Bagga, Arvind, Barbour, Sean J., Barratt, Jonathan, Chan, Daniel T.M., Chang, Anthony, Choo, Jason Chon Jun, Cook, H. Terence, Coppo, Rosanna, Fervenza, Fernando C., Fogo, Agnes B., Fox, Jonathan G., Glassock, Richard J., Harris, David, Hodson, Elisabeth M., Hogan, Jonathan J., Hoxha, Elion, Iseki, Kunitoshi, Jennette, J. Charles, Jha, Vivekanand, Johnson, David W., Kaname, Shinya, Katafuchi, Ritsuko, Kitching, A. Richard, Lafayette, Richard A., Li, Philip K.T., Liew, Adrian, Lv, Jicheng, Malvar, Ana, Maruyama, Shoichi, Mejía-Vilet, Juan Manuel, Mok, Chi Chiu, Nachman, Patrick H., Nester, Carla M., Noiri, Eisei, O'Shaughnessy, Michelle M., Özen, Seza, Parikh, Samir M., Park, Hyeong-Cheon, Peh, Chen Au, Pendergraft, William F., Pickering, Matthew C., Pillebout, Evangéline, Radhakrishnan, Jai, Rathi, Manish, Ronco, Pierre, Smoyer, William E., Tang, Sydney C.W., Tesař, Vladimír, Thurman, Joshua M., Trimarchi, Hernán, Vivarelli, Marina, Walters, Giles D., Wang, Angela Yee-Moon, Wenderfer, Scott E., Wetzels, Jack F.M., Rovin, Brad H., Caster, Dawn J., Cattran, Daniel C., Gibson, Keisha L., Moeller, Marcus J., Roccatello, Dario, Cheung, Michael, Wheeler, David C., Winkelmayer, Wolfgang C., and Floege, Jürgen

Published
2019
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9. Management and treatment of glomerular diseases (part 1): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Author

Adler, Sharon G., Alpers, Charles E., Ayoub, Isabelle, Bagga, Arvind, Barratt, Jonathan, Caster, Dawn J., Chan, Daniel T.M., Chang, Anthony, Choo, Jason Chon Jun, Cook, H. Terence, Coppo, Rosanna, Fervenza, Fernando C., Fogo, Agnes B., Fox, Jonathan G., Gibson, Keisha L., Glassock, Richard J., Harris, David, Hodson, Elisabeth M., Hoxha, Elion, Iseki, Kunitoshi, Jennette, J. Charles, Jha, Vivekanand, Johnson, David W., Kaname, Shinya, Katafuchi, Ritsuko, Kitching, A. Richard, Lafayette, Richard A., Li, Philip K.T., Liew, Adrian, Lv, Jicheng, Malvar, Ana, Maruyama, Shoichi, Mejía-Vilet, Juan Manuel, Moeller, Marcus J., Mok, Chi Chiu, Nester, Carla M., Noiri, Eisei, O'Shaughnessy, Michelle M., Özen, Seza, Parikh, Samir M., Park, Hyeong-Cheon, Peh, Chen Au, Pendergraft, William F., Pickering, Matthew C., Pillebout, Evangéline, Radhakrishnan, Jai, Rathi, Manish, Roccatello, Dario, Ronco, Pierre, Smoyer, William E., Tesař, Vladimír, Thurman, Joshua M., Trimarchi, Hernán, Vivarelli, Marina, Walters, Giles D., Wang, Angela Yee-Moon, Wenderfer, Scott E., Floege, Jürgen, Barbour, Sean J., Cattran, Daniel C., Hogan, Jonathan J., Nachman, Patrick H., Tang, Sydney C.W., Wetzels, Jack F.M., Cheung, Michael, Wheeler, David C., Winkelmayer, Wolfgang C., and Rovin, Brad H.

Published
2019
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11. T cell repertoires in animal and human glomerulonephritis

Author

Walters, Giles

Subjects
616.6120797
Abstract

This thesis aims to study the role of T cells in glomerulonephritis and to take a first step towards design of novel T cell based treatments of these conditions. Two animal models, Heymann nephritis (HN) and experimental autoimmune glomerulonephritis (EAG), are studied. Glomerular T cell receptor (TCR) repertoires from each of these models are analysed using polymerase chain reaction, CDR3 spectratyping and DNA sequencing of their CDR3 regions. In HN, a restricted set of T cells defined by their Vbeta J beta and CDR3 regions are identified as potentially pathogenic cells. In EAG, infiltrating T cells are shown to be clearly oligoclonal with restricted TCR repertoires in each animal. The repertoire restriction differs in each animal studied but the entire population carries multiple TCR CDR3 motifs which are absent in control cells.;The data from HN is utilised to design a DNA vaccination based upon the identified PCR products of infiltrating T cells. Vaccinated rats have significantly improved disease with reduced proteinuria. CD8 + and macrophage infiltration and IFN-gamma. The mechanism of action of DNA vaccination is explored, demonstrating specific anti-TCR antibodies in vaccination rats. The antibodies appear to reduce specific T cell infiltration to the kidneys and to reduce IFN-gamma expression.;Oligoclonal T cells are also identified in archival human renal biopsy tissue. Restricted TCR repertoires are variable but CDR3 spectratypes clearly show oligoclonality within multiple TCR Vbeta families. The data suggest that the most frequently represented T cell mRNA species may account for a large proportion of total T cell receptor mRNA signal.

Published
2005

12. Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial

Author

Smith, Rona M, Jones, Rachel B, Specks, Ulrich, Bond, Simon, Nodale, Marianna, Al-Jayyousi, Reem, Andrews, Jacqueline, Bruchfeld, Annette, Camilleri, Brian, Carette, Simon, Cheung, Chee Kay, Derebail, Vimal, Doulton, Tim, Ferraro, Alastair, Forbess, Lindsy, Fujimoto, Shouichi, Furuta, Shunsuke, Gewurz-Singer, Ora, Harper, Lorraine, Ito-Ihara, Toshiko, Khalidi, Nader, Klocke, Rainer, Koening, Curry, Komagata, Yoshinori, Langford, Carol, Lanyon, Peter, Luqmani, Raashid, McAlear, Carol, Moreland, Larry W, Mynard, Kim, Nachman, Patrick, Pagnoux, Christian, Peh, Chen Au, Pusey, Charles, Ranganathan, Dwarakanathan, Rhee, Rennie L, Spiera, Robert, Sreih, Antoine G, Tesar, Vladamir, Walters, Giles, Wroe, Caroline, Jayne, David, Merkel, Peter A, RITAZAREM Co-Investigators, Smith, Rona M [0000-0002-7438-5156], Nodale, Marianna [0000-0002-0333-8918], Fujimoto, Shouichi [0000-0002-0025-4030], Furuta, Shunsuke [0000-0003-2482-2685], Harper, Lorraine [0000-0003-1343-9234], Khalidi, Nader [0000-0002-8270-2617], Rhee, Rennie L [0000-0002-4907-0304], Spiera, Robert [0000-0003-2911-6800], Walters, Giles [0000-0003-4854-9353], Jayne, David [0000-0002-1712-0637], and Apollo - University of Cambridge Repository

Subjects
granulomatosis with polyangiitis, Remission Induction, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Antineutrophil Cytoplasmic, rituximab, Treatment Outcome, Recurrence, Azathioprine, B-lymphocytes, therapeutics, Humans, systemic vasculitis, Cyclophosphamide, Immunosuppressive Agents
Abstract

Peer reviewed: True, Acknowledgements: The RITAZAREM trial is directed by the European Vasculitis Society and the Vasculitis Clinical Research Consortium (VCRC). The primary sponsor is Cambridge University Hospitals NHS Foundation Trust, and there are collaboration and data-sharing agreements with the University of Pennsylvania and the University of Miyazaki and Okayama University in Japan., Funder: Research Committee on Intractable Vasculitides, the Ministry of Health, Labour and Welfare of Japan, OBJECTIVE: Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab. METHODS: RITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse). RESULTS: Rituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, p

Published
2023
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13. Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus

Author

Jiang, Simon H., Athanasopoulos, Vicki, Ellyard, Julia I., Chuah, Aaron, Cappello, Jean, Cook, Amelia, Prabhu, Savit B., Cardenas, Jacob, Gu, Jinghua, Stanley, Maurice, Roco, Jonathan A., Papa, Ilenia, Yabas, Mehmet, Walters, Giles D., Burgio, Gaetan, McKeon, Kathryn, Byers, James M., Burrin, Charlotte, Enders, Anselm, Miosge, Lisa A., Canete, Pablo F., Jelusic, Marija, Tasic, Velibor, Lungu, Adrian C., Alexander, Stephen I., Kitching, Arthur R., Fulcher, David A., Shen, Nan, Arsov, Todor, Gatenby, Paul A., Babon, Jeff J., Mallon, Dominic F., de Lucas Collantes, Carmen, Stone, Eric A., Wu, Philip, Field, Matthew A., Andrews, Thomas D., Cho, Eun, Pascual, Virginia, Cook, Matthew C., and Vinuesa, Carola G.

Published
2019
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14. Rare SH2B3 coding variants identified in lupus patients impair B cell tolerance and predispose to autoimmunity

Author

Zhang, Yaoyuan, primary, Morris, Rhiannon, additional, Lorenzo, Ayla May D, additional, Meng, Xiangpeng, additional, Kershaw, Nadia J, additional, Kiridena, Pamudika, additional, Brown, Grant J, additional, Burgio, Gaetan, additional, Cappello, Jean Y, additional, Shen, Qian, additional, Wang, Hao, additional, Turnbull, Cynthia M, additional, Lea-Henry, Tom, additional, Stanley, Maurice, additional, Yu, Zhijia, additional, Ballard, Fiona, additional, Chuah, Aaron, additional, Lee, James C, additional, Hatch, Ann-Maree, additional, Headley, Alexander P, additional, Trnka, Peter, additional, Mallon, Dominic, additional, Fletcher, Jeffery T, additional, Walters, Giles D, additional, Sestan, Mario, additional, Jelusic, Marija, additional, Cook, Matthew C, additional, Athanasopoulos, Vicki, additional, Fulcher, David A, additional, Babon, Jeffrey J, additional, Vinuesa, Carola G, additional, and Ellyard, Julia I, additional

Published
2023
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16. Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial

Author

Smith, Rona M, primary, Jones, Rachel B, additional, Specks, Ulrich, additional, Bond, Simon, additional, Nodale, Marianna, additional, Al-jayyousi, Reem, additional, Andrews, Jacqueline, additional, Bruchfeld, Annette, additional, Camilleri, Brian, additional, Carette, Simon, additional, Cheung, Chee Kay, additional, Derebail, Vimal, additional, Doulton, Tim, additional, Ferraro, Alastair, additional, Forbess, Lindsy, additional, Fujimoto, Shouichi, additional, Furuta, Shunsuke, additional, Gewurz-Singer, Ora, additional, Harper, Lorraine, additional, Ito-Ihara, Toshiko, additional, Khalidi, Nader, additional, Klocke, Rainer, additional, Koening, Curry, additional, Komagata, Yoshinori, additional, Langford, Carol, additional, Lanyon, Peter, additional, Luqmani, Raashid, additional, McAlear, Carol, additional, Moreland, Larry W, additional, Mynard, Kim, additional, Nachman, Patrick, additional, Pagnoux, Christian, additional, Peh, Chen Au, additional, Pusey, Charles, additional, Ranganathan, Dwarakanathan, additional, Rhee, Rennie L, additional, Spiera, Robert, additional, Sreih, Antoine G, additional, Tesar, Vladamir, additional, Walters, Giles, additional, Wroe, Caroline, additional, Jayne, David, additional, and Merkel, Peter A, additional

Published
2023
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17. Immunophenotyping identifies distinct cellular signatures for systemic lupus erythematosus and lupus nephritis

Author

Aw, Yi Tong V., primary, Whiley, Phillip J., additional, Lorenzo, Ayla May, additional, Lea‐Henry, Tom, additional, Shanmuganandam, Somasundhari, additional, Stanley, Maurice, additional, Babu, Sonia N., additional, Athanasopoulos, Vicki, additional, Cappello, Jean, additional, Ellyard, Julia I., additional, Cook, Matthew, additional, Vinuesa, Carola, additional, Walters, Giles, additional, Fulcher, David A., additional, and Jiang, Simon H., additional

Published
2022
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18. The effects of plasma exchange and glucocorticoids on early kidney function among patients with ANCA-associated vasculitis in the PEXIVAS trial

Author

Odler, Balazs, Riedl, Regina, Geetha, Duvuru, Szpirt, Wladimir M., Hawley, Carmel, Uchida, Lisa, Wallace, Zachary S., Walters, Giles, Muso, Eri, Tesar, Vladimir, Pusey, Charles D., Little, Mark A., Merkel, Peter A., Walsh, Michael, Jayne, David R.W., Kronbichler, Andreas, Paizis, Kathy, Walters, Giles, Jardine, Meg, Milton, Caroline, Ibraham, Abu, Siva, Brian, Desmond, Michael, Perkovic, Vlado, Kurtkoti, Jadadeesh, Vilayur, Eswari, Cass, Alan, Summers, Shaun, Brown, Fiona, Ryan, Jessica, Kerr, Peter, Noble, Euan, Luxton, Grant, Mudge, David W., Hawley, Carmel, Johnson, David W., Peh, Chen Au, Faull, Randall J., Ranganathan, Dwarakanathan, Jeffs, Lisa, Nicholls, Kathy, Hughes, Peter, Cooper, Bruce, Boudville, Neil, Ford, Sharon, Langham, Robyn, Reidlinger, Donna, AliciaMorrish, Badve, Sunil V., Pascoe, Elaine, Paul-Brent, Peta-Anne, Robison, Laura, Valks, Andrea, Blockmans, Daniel, Henckaerts, Liesbet, Sprangers, Ben, Suri, Rita, Brachemi, Soumeya, Clark, William, Garg, Amit, Carette, Simon, Pagnoux, Christian, Reich, Heather, Barth, David, Walsh, Michael, Khalidi, Nader, Cox, Gerry, Mazzetti, Andrea, Robins, Diane, Wald, Ron, Perl, Jeffrey, Pavenski, Katerina, Dacouris, Niki, Levin, Adeera, Copland, Michael, Fairhead, Todd, Pannu, Neesh, Qarni, Muhammad Uwais, Habib, Syed, Girard, Louis, Manns, Braden, Tesar, Vladimir, Hruskova, Zdenka, Chocova, Zdenka, Povlsen, Johan, Gregersen, Jon, Ivarsen, Per, Birn, Henrik, Krarup, Elizabeth, Pedersen, Erling B., Thomsen, Ingrid, Bech, Jesper Nørgaard, Szpirt, Wladmir, Egfjord, Martin, Mesbah, Rafik, Bataille, Pierre, Rey, Isabelle, Chantrel, François, Vanhille, Philipe, Quémeneur, Thomas, Carron, Pierre-Louis, Zaoui, Philippe, de Moreuil, Claire, Gosselin, Morgane, Delluc, Aurélien, Hanrotel-Saliou, Catherine, Le Jeune, Mathilde, Ficheux, Maxence, Aniort, Julien, Lavigne, Christian, Augusto, Jean Francois, Chauveau, Dominique, Guitard, Joëlle, Huart, Antoine, Ribes, David, Gatault, Philippe, Becmeur, Camille, Muller, Sandrine, Betz, Valérie, Klein, Alexandre, Blaison, Gilles, Seror, Raphaele, Francois, Hélène, Mariette, Xavier, Aubrun, Aurore, Coustet, Baptiste, Palazzo, Elisabeth, Ottaviani, Sébastien, Goulenok, Tiphaine, Daugas, Eric, Dieudé, Philipe, Papo, Thomas, Lebas, Céline, Lionet, Arnaud, Guillevin, Loïc, Mouthon, Luc, Puéchal, Xavier, Jourde-Chiche, Noémie, Ruivard, Marc, Karras, Alexandre, Limal, Nicolas, Kofman, Thomas, Le Quellec, Alain, Maurier, François, Gibelin, Aude, Parrot, Antoine, Bachmeyer, Claude, Gombert, Bruno, Nouvier, Mathilde, Lega, Jean-Christophe, Fain, Olivier, Andrès, Emmanuel, Cottet, Rachel, Gregorini, Gina, Jeannin, Guido, Possenti, Stefano, Buzio, Carlo, Vaglio, Augusto, Oliva, Elena, Makino, Hirofumi, Muso, Eri, Endo, Tomomi, Kakita, Hiroko, Suzuki, Hiroyuki, Handa, Takaya, Kang, Youngna, Ariyasu, Yuki, Tsukamoto, Tatsuo, Endo, Shuichiro, Miyata, Hitomi, Yamada, Hiroyuki, Ito-Ihara, Toshiko, Uchida, Shunya, Kono, Hajime, Fujigaki, Yoshihide, Kikuchi, Hirotoshi, Nanki, Toshihiro, Kato, Hideki, Okamoto, Akiko, Asako, Kurumi, Suzuki, Kazuo, Hamano, Yoshitomo, Yamagata, Kunihiro, Usui, Joichi, Fujimoto, Shouichi, Sato, Yuji, Kikuchi, Masao, Flores-Suárez, Luis Felipe, Sánchez-Guerrero, Sergio A., Collins, Michael, Schollum, John, de Zoysa, Janak, Quincy, Vicki, Sizeland, Peter, Aasarod, Knut, Solbu, Marit, Bruun, Trude Jannecke, Koldingsnes, Wenche, Wludarczyk, Anna, Nowak, Ilona, Gorka, Jacek, Sznajd, Jan, Padjas, Agnieszka, Jankowski, Milosz, Widawska, Agnieszka, Szczeklik, Wojciech, Ballarin, Jose, Bruchfeld, Annette, Efvergren, Mats, Eriksson, Per, Westman, Kerstin, Selga, Daina, Heijl, Caroline, Ohlsson, Sophie, Segelmark, Marten, Basu, Neil, Kidder, Dana, Fluck, Nicholas, Jayne, David R.W., Smith, Rona, Wilcocks, Lisa, McClure, Mark, Jones, Rachel, Trivedi, Sapna, Gopaluni, Seerapani, Brettell, Elizabeth, Crump, Paul, Feilbach, Annika, Hewitt, Catherine, Hilken, Nick, Howman, Andrew, Hughes, Terry, Ives, Natalie, Jarrett, Hugh, Mehta, Samir, Record, Rebecca, Ryan, Gemma, Sidile, Chaka, Wheatley, Keith, Sheerin, Brown, Alison, Baines, Laura Anne, Lordan, Jim, Pusey, Charles, Tanna, Anisha, McAdoo, Stephen, Levy, Jeremy, Griffith, Megan, Klebe, Bernhard, Doulton, Timothy, Warwick, Graham, Burton, James, Barratt, Jonathon, Topham, Peter, Baines, Richard, Brunskill, Nigel, Al-Jayyousi, Reem, Hamilton, Patrick, Patel, Mumtaz, Mitra, Sandip, Brown, Nina, Sharples, Edward, Luqmani, Raashid, Harper, Lorraine, Rhodes, Benjamin, Chanouzas, Dimitrios, Morgan, Matthew, Hewins, Peter, Floßmann, Oliver, Bhandary, Nitin, Foxton, Julie, Jones, Linda, King, Jenny, Smyth, Lucy, D’Souza, Richard, Haigh, Richard, Hough, Maxine, Smyth, Lucy, Haigh, Richard, Hough, Maxine, Salama, Alan, Burns, Aine, Little, Mark, Dhaun, Neeraj, Dhaygude, Ajay, Basnayake, Kolitha, Iggo, Neil, Jones, Daniel, Oliveira, David, MacPhee, Iain A.M., Dunn, Emma, Lewington, Andrew J.P., Fan, Stanley Linsun, Rajakariar, Ravindra, Yaqoob, Magdi, Short, Andrew, Geddes, Colin, Mackinnon, Bruce, Jardine, Alan G., Monach, Paul, Merkel, Peter A., Amudala, Naomi, Quillen, Karen, Weisman, Michael, Wallace, Daniel, Forbess, Lindsy, Venuturupalli, Swamy, Langford, Carol, Hajj-Ali, Rula, Koo, Anna, Hoffman, Gary, Specks, Ulrich, Keogh, Karina, Ytterberg, Steven, Winters, Jeff, Warrington, Kenneth, Cartin-Ceba, Rodrigo, Peikert, Tobias, Fervenza, Fernando, Baqir, Misbah, Nachman, Patrick, Detwiler, Randy, Mottl, Amy, Derebail, Vimal, McGregor, JulieAnne, Merkel, Peter A., Sreih, Antoine, Rhee, Rennie, McAlear, Carol, Aqui, Nicole, Moreland, Larry, Kiss, Joseph, Liang, Kimberly, Mohan, Niveditha, Balogun, Rasheed, Li, Tingting, and Brasington, Richard

Abstract

Therapeutic plasma exchange (PLEX) is an adjunctive treatment for patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and kidney involvement. Little is known about the effect of PLEX on early changes in kidney function. This post-hocanalysis of the PEXIVAS trial investigated the effects of PLEX on changes in kidney function within 12 months. PEXIVAS was a randomized controlled trial recruiting 691 patients with ANCA-associated glomerulonephritis, of whom 349 underwent PLEX and 342 received no-PLEX. The primary outcomes of this post hocstudy of PEXIVAS were change in estimated glomerular filtration rate (eGFR) from baseline and recovery of kidney function (defined as eGFR increase of 15ml/min/1.73m2or more). Baseline eGFR was 21.7 ± 20.3 and 20.6 ± 18.7 ml/min/1.73m2in the PLEX and no-PLEX groups, respectively. Mean improvements in eGFR at weeks two, four, and eight after initiation of therapy were greater for the PLEX vs. the no-PLEX groups. The greatest significant difference in recovery of kidney function in the PLEX compared to the no-PLEX groups was at week four (relative risk (RR): 1.41; 95% confidence interval:1.09-1.82). Increased eGFR or recovery of kidney function at week four were significantly associated with lower risk for end-stage kidney disease at week 52 (RR: 0.96: 0.95-0.97, and RR: 0.29: 0.16-0.52; respectively). Neither changes in eGFR nor recovery of kidney function differed by reduced- compared to standard-dose glucocorticoid group. Overall, our study indicates that PLEX improves early kidney function in patients with ANCA-associated glomerulonephritis.

Published
2025
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19. Role of therapeutic plasmapheresis in ANCA-associated vasculitis

Author

Walters, Giles

Subjects
Vasculitis -- Research -- Risk factors -- Care and treatment -- Complications and side effects -- Patient outcomes, Plasmapheresis -- Research, Health
Abstract

Plasma exchange, or plasmapheresis, is a treatment method that developed over a period of two decades and involves the removal and replacement of a patient's circulating plasma. The aim of treatment is to remove disease-associated molecules and therefore interrupt disease progression. This article summarizes the developmental history of this treatment and then looks in more detail at data on the use of plasma exchange in treating antineutrophil antibody (ANCA)-associated vasculitis. The eight randomized trials and the Cochrane Systematic Review on treating renal vasculitis are summarized to show that plasma exchange may be effective in this disease, specifically in reducing the development of end-stage kidney disease (ESKD) by approximately 40 %. The plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS) study is a currently enrolling study aiming to answer some of the outstanding questions relating to the use of this treatment in ANCA-associated vasculitis., Author(s): Giles Walters[sup.1] [sup.2] Author Affiliations: (1) Department of Renal Medicine, Canberra Hospital, Garran, ACT, Australia (2) Australian National University Medical School, Canberra, ACT, Australia Introduction This article aims to [...]

Published
2016
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23. Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis

Author

Smith, Rona M, Jones, Rachel Bronwen, Specks, Ulrich, Bond, Simon, Nodale, Marianna, Aljayyousi, Reem, Andrews, Jacqueline, Bruchfeld, Annette, Camilleri, Brian, Carette, Simon, Cheung, Chee Kay, Derebail, Vimal, Doulton, Tim, Forbess, Lindsy, Fujimoto, Shouichi, Furuta, Shunsuke, Gewurz-Singer, Ora, Harper, Lorraine, Ito-Ihara, Toshiko, Khalidi, Nader, Klocke, Rainer, Koening, Curry, Komagata, Yoshinori, Langford, Carol, Lanyon, Peter, Luqmani, Raashid Ahmed, Makino, Hirofumi, McAlear, Carole, Monach, Paul, Moreland, Larry W, Mynard, Kim, Nachman, Patrick, Pagnoux, Christian, Pearce, Fiona, Peh, Chen Au, Pusey, Charles, Ranganathan, Dwarakanathan, Rhee, Rennie L, Spiera, Robert, Sreih, Antoine G, Tesar, Vladimir, Walters, Giles, Weisman, Michael H, Wroe, Caroline, Merkel, Peter, Jayne, David, RITAZAREM Co-Investigators, Arimura, Y, Clarkson, M, De Zoysa, J, Endo, T, Hamano, Y, Kono, H, Lawman, S, Muso, E, Sada, K, Smith, R, Suzuki, K, Tsukamoto, T, Uchida, S, Vaglio, A, Watts, R, Smith, Rona M [0000-0002-7438-5156], Jones, Rachel Bronwen [0000-0003-4790-283X], Nodale, Marianna [0000-0002-0333-8918], Harper, Lorraine [0000-0003-1343-9234], Rhee, Rennie L [0000-0002-4907-0304], Walters, Giles [0000-0003-4854-9353], and Apollo - University of Cambridge Repository

Subjects
Vasculitis, B cells, granulomatosis with polyangiitis, treatment, systemic vasculitis
Abstract

Funder: Research Committee on Intractable Vasculitides; The Ministry of Health, Labour and Welfare of Japan., Objectives: Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial. Methods: Patients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m2) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse. Results: 188 patients were studied: 95/188 (51%) men, median age 59 years (range 19–89), prior disease duration 5.0 years (range 0.4–34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections. Conclusions: This large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies.

Published
2020
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24. Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease

Author

Jiang, Simon H., primary, Mercan, Sevcan, additional, Papa, Ilenia, additional, Moldovan, Max, additional, Walters, Giles D., additional, Koina, Mark, additional, Fadia, Mitali, additional, Stanley, Maurice, additional, Lea-Henry, Tom, additional, Cook, Amelia, additional, Ellyard, Julia, additional, McMorran, Brendan, additional, Sundaram, Madhivanan, additional, Thomson, Russell, additional, Canete, Pablo F., additional, Hoy, Wendy, additional, Hutton, Holly, additional, Srivastava, Monika, additional, McKeon, Kathryn, additional, de la Rúa Figueroa, Iñigo, additional, Cervera, Ricard, additional, Faria, Raquel, additional, D’Alfonso, Sandra, additional, Gatto, Mariele, additional, Athanasopoulos, Vicki, additional, Field, Matthew, additional, Mathews, John, additional, Cho, Eun, additional, Andrews, Thomas D., additional, Kitching, A. Richard, additional, Cook, Matthew C., additional, Riquelme, Marta Alarcon, additional, Bahlo, Melanie, additional, and Vinuesa, Carola G., additional

Published
2021
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25. sj-pdf-2-lup-10.1177_09612033211033979 - Supplemental material for Increased burden of rare variants in genes of the endosomal Toll-like receptor pathway in patients with systemic lupus erythematosus

Author

Lea-Henry, Tom N, Chuah, Aaron, Stanley, Maurice, Athanasopoulos, Vicki, Starkey, Malcolm R, Christiadi, Daniel, Kitching, A Richard, Cook, Matthew C, Andrews, Thomas D, Vinuesa, Carola G, Walters, Giles D, and Jiang, Simon H

Subjects
111702 Aged Health Care, FOS: Health sciences, skin and connective tissue diseases, humanities
Abstract

Supplemental material, sj-pdf-2-lup-10.1177_09612033211033979 for Increased burden of rare variants in genes of the endosomal Toll-like receptor pathway in patients with systemic lupus erythematosus by Tom N Lea-Henry, Aaron Chuah, Maurice Stanley, Vicki Athanasopoulos, Malcolm R Starkey, Daniel Christiadi, A Richard Kitching, Matthew C Cook, Thomas D Andrews, Carola G Vinuesa, Giles D Walters and Simon H Jiang in Lupus

Published
2021
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26. sj-pdf-1-lup-10.1177_09612033211033979 - Supplemental material for Increased burden of rare variants in genes of the endosomal Toll-like receptor pathway in patients with systemic lupus erythematosus

Author

Lea-Henry, Tom N, Chuah, Aaron, Stanley, Maurice, Athanasopoulos, Vicki, Starkey, Malcolm R, Christiadi, Daniel, Kitching, A Richard, Cook, Matthew C, Andrews, Thomas D, Vinuesa, Carola G, Walters, Giles D, and Jiang, Simon H

Subjects
111702 Aged Health Care, FOS: Health sciences, skin and connective tissue diseases, humanities
Abstract

Supplemental material, sj-pdf-1-lup-10.1177_09612033211033979 for Increased burden of rare variants in genes of the endosomal Toll-like receptor pathway in patients with systemic lupus erythematosus by Tom N Lea-Henry, Aaron Chuah, Maurice Stanley, Vicki Athanasopoulos, Malcolm R Starkey, Daniel Christiadi, A Richard Kitching, Matthew C Cook, Thomas D Andrews, Carola G Vinuesa, Giles D Walters and Simon H Jiang in Lupus

Published
2021
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27. sj-pdf-3-lup-10.1177_09612033211033979 - Supplemental material for Increased burden of rare variants in genes of the endosomal Toll-like receptor pathway in patients with systemic lupus erythematosus

Author

Lea-Henry, Tom N, Chuah, Aaron, Stanley, Maurice, Athanasopoulos, Vicki, Starkey, Malcolm R, Christiadi, Daniel, Kitching, A Richard, Cook, Matthew C, Andrews, Thomas D, Vinuesa, Carola G, Walters, Giles D, and Jiang, Simon H

Subjects
111702 Aged Health Care, FOS: Health sciences, skin and connective tissue diseases, humanities
Abstract

Supplemental material, sj-pdf-3-lup-10.1177_09612033211033979 for Increased burden of rare variants in genes of the endosomal Toll-like receptor pathway in patients with systemic lupus erythematosus by Tom N Lea-Henry, Aaron Chuah, Maurice Stanley, Vicki Athanasopoulos, Malcolm R Starkey, Daniel Christiadi, A Richard Kitching, Matthew C Cook, Thomas D Andrews, Carola G Vinuesa, Giles D Walters and Simon H Jiang in Lupus

Published
2021
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28. Increased burden of rare variants in genes of the endosomal Toll-like receptor pathway in patients with systemic lupus erythematosus

Author

Lea-Henry, Tom N, primary, Chuah, Aaron, additional, Stanley, Maurice, additional, Athanasopoulos, Vicki, additional, Starkey, Malcolm R, additional, Christiadi, Daniel, additional, Kitching, A Richard, additional, Cook, Matthew C, additional, Andrews, Thomas D, additional, Vinuesa, Carola G, additional, Walters, Giles D, additional, and Jiang, Simon H, additional

Published
2021
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30. Effects of Allopurinol on the Progression of Chronic Kidney Disease

Author

Badve, Sunil V., primary, Pascoe, Elaine M., additional, Tiku, Anushree, additional, Boudville, Neil, additional, Brown, Fiona G., additional, Cass, Alan, additional, Clarke, Philip, additional, Dalbeth, Nicola, additional, Day, Richard O., additional, de Zoysa, Janak R., additional, Douglas, Bettina, additional, Faull, Randall, additional, Harris, David C., additional, Hawley, Carmel M., additional, Jones, Graham R.D., additional, Kanellis, John, additional, Palmer, Suetonia C., additional, Perkovic, Vlado, additional, Rangan, Gopala K., additional, Reidlinger, Donna, additional, Robison, Laura, additional, Walker, Robert J., additional, Walters, Giles, additional, and Johnson, David W., additional

Published
2020
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31. Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis

Author

Smith, Rona M, primary, Jones, Rachel Bronwen, additional, Specks, Ulrich, additional, Bond, Simon, additional, Nodale, Marianna, additional, Aljayyousi, Reem, additional, Andrews, Jacqueline, additional, Bruchfeld, Annette, additional, Camilleri, Brian, additional, Carette, Simon, additional, Cheung, Chee Kay, additional, Derebail, Vimal, additional, Doulton, Tim, additional, Forbess, Lindsy, additional, Fujimoto, Shouichi, additional, Furuta, Shunsuke, additional, Gewurz-Singer, Ora, additional, Harper, Lorraine, additional, Ito-Ihara, Toshiko, additional, Khalidi, Nader, additional, Klocke, Rainer, additional, Koening, Curry, additional, Komagata, Yoshinori, additional, Langford, Carol, additional, Lanyon, Peter, additional, Luqmani, Raashid Ahmed, additional, Makino, Hirofumi, additional, McAlear, Carole, additional, Monach, Paul, additional, Moreland, Larry W, additional, Mynard, Kim, additional, Nachman, Patrick, additional, Pagnoux, Christian, additional, Pearce, Fiona, additional, Peh, Chen Au, additional, Pusey, Charles, additional, Ranganathan, Dwarakanathan, additional, Rhee, Rennie L, additional, Spiera, Robert, additional, Sreih, Antoine G, additional, Tesar, Vladimir, additional, Walters, Giles, additional, Weisman, Michael H, additional, Wroe, Caroline, additional, Merkel, Peter, additional, and Jayne, David, additional

Published
2020
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38. TLR7gain-of-function genetic variation causes human lupus

Author

Brown, Grant J., Cañete, Pablo F., Wang, Hao, Medhavy, Arti, Bones, Josiah, Roco, Jonathan A., He, Yuke, Qin, Yuting, Cappello, Jean, Ellyard, Julia I., Bassett, Katharine, Shen, Qian, Burgio, Gaetan, Zhang, Yaoyuan, Turnbull, Cynthia, Meng, Xiangpeng, Wu, Phil, Cho, Eun, Miosge, Lisa A., Andrews, T. Daniel, Field, Matt A., Tvorogov, Denis, Lopez, Angel F., Babon, Jeffrey J., López, Cristina Aparicio, Gónzalez-Murillo, África, Garulo, Daniel Clemente, Pascual, Virginia, Levy, Tess, Mallack, Eric J., Calame, Daniel G., Lotze, Timothy, Lupski, James R., Ding, Huihua, Ullah, Tomalika R., Walters, Giles D., Koina, Mark E., Cook, Matthew C., Shen, Nan, de Lucas Collantes, Carmen, Corry, Ben, Gantier, Michael P., Athanasopoulos, Vicki, and Vinuesa, Carola G.

Abstract

Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease1–7, evidence of lupus-causing TLR7gene variants is lacking. Here we describe human systemic lupus erythematosus caused by a TLR7gain-of-function variant. TLR7 is a sensor of viral RNA8,9and binds to guanosine10–12. We identified a de novo, previously undescribed missense TLR7Y264Hvariant in a child with severe lupus and additional variants in other patients with lupus. The TLR7Y264Hvariant selectively increased sensing of guanosine and 2',3'-cGMP10–12, and was sufficient to cause lupus when introduced into mice. We show that enhanced TLR7 signalling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c+age-associated B cells and germinal centre B cells. Follicular and extrafollicular helper T cells were also increased but these phenotypes were cell-extrinsic. Deficiency of MyD88 (an adaptor protein downstream of TLR7) rescued autoimmunity, aberrant B cell survival, and all cellular and serological phenotypes. Despite prominent spontaneous germinal-centre formation in Tlr7Y264Hmice, autoimmunity was not ameliorated by germinal-centre deficiency, suggesting an extrafollicular origin of pathogenic B cells. We establish the importance of TLR7 and guanosine-containing self-ligands for human lupus pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.

Published
2022
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39. Interventions for renal vasculitis in adults. A systematic review

Author

Craig Jonathan C, Willis Narelle S, and Walters Giles D

Subjects
Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney failure, haematuria and proteinuria. Treatment of these conditions involves the use of steroid and non-steroid agents with or without adjunctive plasma exchange. Although immunosuppression has been successful, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This systematic review was conducted to determine the benefits and harms of any intervention for the treatment of renal vasculitis in adults. Methods We searched the Cochrane Central Register of Controlled Trials, the Cochrane Renal Group Specialised Register, MEDLINE and EMBASE to June 2009. Randomised controlled trials investigating any intervention for the treatment of adults were included. Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio with 95% confidence intervals for dichotomous outcomes or mean difference for continuous outcomes. Results Twenty two studies (1674 patients) were included. Plasma exchange as adjunctive therapy significantly reduces the risk of end-stage kidney disease at 12 months (five studies: RR 0.47, CI 0.30 to 0.75). Four studies compared the use of pulse and continuous administration of cyclophosphamide. Remission rates were equivalent but pulse treatment causes an increased risk of relapse (4 studies: RR 1.79, CI 1.11 to 2.87) compared with continuous cyclophosphamide. Azathioprine has equivalent efficacy as a maintenance agent to cyclophosphamide with fewer episodes of leukopenia. Mycophenolate mofetil may be equivalent to cyclophosphamide as an induction agent but resulted in a higher relapse rate when tested against Azathioprine in remission maintenance. Rituximab is an effective remission induction agent. Methotrexate or Leflunomide are potential choices in remission maintenance therapy. Oral co-trimoxazole did not reduce relapses significantly in Wegener's granulomatosis. Conclusions Plasma exchange is effective in patients with severe ARF secondary to vasculitis. Pulse cyclophosphamide results in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst cyclophosphamide is standard induction treatment, rituximab and mycophenolate mofetil are also effective. Azathioprine, methotrexate and leflunomide are effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.

Published
2010
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40. Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus

Author

Jiang, Simon, Athanasopoulos, Vicki, Ellyard, Julia, Chuah, Lay Hong, Cappello, Jean, Cook, Amelia, Prabhu, Savit, Cardenas, Jacob, Gu, Jinghua, Stanley, Maurice, Roco Alegre, Jonathan, Papa, Ilenia, Yabas, Mehmet, Walters, Giles, Burgio, Gaetan, McKeon, Kathryn, Byers, James, Burrin, Charlotte, Enders, Anselm, Miosge, Lisa, Canete, Pablo, Jelusic, Marija, Tasic, Velibor, Lungu, Adrian C., Alexander, Stephen, Kitching, Arthur, Fulcher, David, Shen, Nan, Arsov, Todor, Gatenby, Paul, Babon, Jeffrey J., Mallon, Dominic F., de Lucas Collantes, Carmen, Stone, Eric, Wu, Philip, Field, Matthew, Andrews, Thomas (Dan), Cho, Eun, Pascual, Virginia, Cook, Matthew, Garcia De Vinuesa, Maria Carola, Jiang, Simon, Athanasopoulos, Vicki, Ellyard, Julia, Chuah, Lay Hong, Cappello, Jean, Cook, Amelia, Prabhu, Savit, Cardenas, Jacob, Gu, Jinghua, Stanley, Maurice, Roco Alegre, Jonathan, Papa, Ilenia, Yabas, Mehmet, Walters, Giles, Burgio, Gaetan, McKeon, Kathryn, Byers, James, Burrin, Charlotte, Enders, Anselm, Miosge, Lisa, Canete, Pablo, Jelusic, Marija, Tasic, Velibor, Lungu, Adrian C., Alexander, Stephen, Kitching, Arthur, Fulcher, David, Shen, Nan, Arsov, Todor, Gatenby, Paul, Babon, Jeffrey J., Mallon, Dominic F., de Lucas Collantes, Carmen, Stone, Eric, Wu, Philip, Field, Matthew, Andrews, Thomas (Dan), Cho, Eun, Pascual, Virginia, Cook, Matthew, and Garcia De Vinuesa, Maria Carola

Abstract

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.

Published
2019

41. Management and treatment of glomerular diseases (part 2): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Author

Rovin, Brad H., primary, Caster, Dawn J., additional, Cattran, Daniel C., additional, Gibson, Keisha L., additional, Hogan, Jonathan J., additional, Moeller, Marcus J., additional, Roccatello, Dario, additional, Cheung, Michael, additional, Wheeler, David C., additional, Winkelmayer, Wolfgang C., additional, Floege, Jürgen, additional, Adler, Sharon G., additional, Alpers, Charles E., additional, Ayoub, Isabelle, additional, Bagga, Arvind, additional, Barbour, Sean J., additional, Barratt, Jonathan, additional, Chan, Daniel T.M., additional, Chang, Anthony, additional, Choo, Jason Chon Jun, additional, Cook, H. Terence, additional, Coppo, Rosanna, additional, Fervenza, Fernando C., additional, Fogo, Agnes B., additional, Fox, Jonathan G., additional, Glassock, Richard J., additional, Harris, David, additional, Hodson, Elisabeth M., additional, Hoxha, Elion, additional, Iseki, Kunitoshi, additional, Jennette, J. Charles, additional, Jha, Vivekanand, additional, Johnson, David W., additional, Kaname, Shinya, additional, Katafuchi, Ritsuko, additional, Kitching, A. Richard, additional, Lafayette, Richard A., additional, Li, Philip K.T., additional, Liew, Adrian, additional, Lv, Jicheng, additional, Malvar, Ana, additional, Maruyama, Shoichi, additional, Mejía-Vilet, Juan Manuel, additional, Mok, Chi Chiu, additional, Nachman, Patrick H., additional, Nester, Carla M., additional, Noiri, Eisei, additional, O'Shaughnessy, Michelle M., additional, Özen, Seza, additional, Parikh, Samir M., additional, Park, Hyeong-Cheon, additional, Peh, Chen Au, additional, Pendergraft, William F., additional, Pickering, Matthew C., additional, Pillebout, Evangéline, additional, Radhakrishnan, Jai, additional, Rathi, Manish, additional, Ronco, Pierre, additional, Smoyer, William E., additional, Tang, Sydney C.W., additional, Tesař, Vladimír, additional, Thurman, Joshua M., additional, Trimarchi, Hernán, additional, Vivarelli, Marina, additional, Walters, Giles D., additional, Wang, Angela Yee-Moon, additional, Wenderfer, Scott E., additional, and Wetzels, Jack F.M., additional

Published
2019
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42. Management and treatment of glomerular diseases (part 1): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Author

Floege, Jürgen, primary, Barbour, Sean J., additional, Cattran, Daniel C., additional, Hogan, Jonathan J., additional, Nachman, Patrick H., additional, Tang, Sydney C.W., additional, Wetzels, Jack F.M., additional, Cheung, Michael, additional, Wheeler, David C., additional, Winkelmayer, Wolfgang C., additional, Rovin, Brad H., additional, Adler, Sharon G., additional, Alpers, Charles E., additional, Ayoub, Isabelle, additional, Bagga, Arvind, additional, Barratt, Jonathan, additional, Caster, Dawn J., additional, Chan, Daniel T.M., additional, Chang, Anthony, additional, Choo, Jason Chon Jun, additional, Cook, H. Terence, additional, Coppo, Rosanna, additional, Fervenza, Fernando C., additional, Fogo, Agnes B., additional, Fox, Jonathan G., additional, Gibson, Keisha L., additional, Glassock, Richard J., additional, Harris, David, additional, Hodson, Elisabeth M., additional, Hoxha, Elion, additional, Iseki, Kunitoshi, additional, Jennette, J. Charles, additional, Jha, Vivekanand, additional, Johnson, David W., additional, Kaname, Shinya, additional, Katafuchi, Ritsuko, additional, Kitching, A. Richard, additional, Lafayette, Richard A., additional, Li, Philip K.T., additional, Liew, Adrian, additional, Lv, Jicheng, additional, Malvar, Ana, additional, Maruyama, Shoichi, additional, Mejía-Vilet, Juan Manuel, additional, Moeller, Marcus J., additional, Mok, Chi Chiu, additional, Nester, Carla M., additional, Noiri, Eisei, additional, O'Shaughnessy, Michelle M., additional, Özen, Seza, additional, Parikh, Samir M., additional, Park, Hyeong-Cheon, additional, Peh, Chen Au, additional, Pendergraft, William F., additional, Pickering, Matthew C., additional, Pillebout, Evangéline, additional, Radhakrishnan, Jai, additional, Rathi, Manish, additional, Roccatello, Dario, additional, Ronco, Pierre, additional, Smoyer, William E., additional, Tesař, Vladimír, additional, Thurman, Joshua M., additional, Trimarchi, Hernán, additional, Vivarelli, Marina, additional, Walters, Giles D., additional, Wang, Angela Yee-Moon, additional, and Wenderfer, Scott E., additional

Published
2019
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43. Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial

Author

Jones, Rachel B, primary, Hiemstra, Thomas F, additional, Ballarin, Jose, additional, Blockmans, Daniel Engelbert, additional, Brogan, Paul, additional, Bruchfeld, Annette, additional, Cid, Maria C, additional, Dahlsveen, Karen, additional, de Zoysa, Janak, additional, Espigol-Frigolé, Georgína, additional, Lanyon, Peter, additional, Peh, Chen Au, additional, Tesar, Vladimir, additional, Vaglio, Augusto, additional, Walsh, Michael, additional, Walsh, Dorothy, additional, Walters, Giles, additional, Harper, Lorraine, additional, and Jayne, David, additional

Published
2019
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45. Recurrent glomerulonephritis following renal transplantation and impact on graft survival

Author

Jiang, Simon, Kennard, Alice, Walters, Giles, Jiang, Simon, Kennard, Alice, and Walters, Giles

Abstract

BackgroundRecurrence of primary glomerulonephritis in the post-transplant period has been described in the literature but the risk remains poorly quantified and its impact on allograft outcomes and implications for subsequent transplants remain under-examined. Here we describe the rates and timing of post-transplant glomerulonephritis recurrence for IgA nephropathy, focal segmental glomerulosclerosis, mesangiocapillary GN and membranous GN based on 28years of ANZDATA registry transplant data.MethodsWe investigated the rates of GN recurrence and subsequent graft outcomes in 7236 patient from 28 years of ANZDATA transplant registry data. Data were analysed in R, using Kaplan Meier Survival analysis and adjusted analyses performed using Cox Proportional Hazards methods. A competing risk model was also analysed.ResultsGN recurrence occurred in 10.5% of transplants and was most common in mesangiocapillary GN. Median time to recurrence was shorter for FSGS compared to IGAN. GN recurrence was less common in patients over 50years of age and after unrelated kidney donation. We identified a significantly higher risk of recurrence in secondary grafts following recurrence in a primary allograft for FSGS (RR 5.70, 95 CI: 2.41-13.5, p<0.001) but not IGAN, MCGN or MN. At 10years, recurrence occurs in 8.7, 10.8, 13.1, and 13.4% of allografts for FSGS, IGAN, MCGN and MN respectively. In all GN, recurrence significantly reduced death censored graft survival at 5 and 10years.ConclusionsGN recurrence occurs in a minority of patients at a significantly different rate for each GN. After a recurrence, there is no evidence for an increased risk of further recurrence in a subsequent graft except in FSGS.

Published
2018

50. Placebo-controlled, randomized clinical trial of high-dose cholecalciferol in renal dialysis patients: effect on muscle strength and quality of life.

Author

Singer, Richard, Chacko, Bobby, Talaulikar, Girish, Karpe, Krishna, and Walters, Giles

Abstract

Background The importance of vitamin D sufficiency in deficient dialysis patients is uncertain. This study aimed to determine if high-dose cholecalciferol for 1-year affected symptoms, muscle strength, blood pressure (BP), cardiac ischaemia, parathyroid hormone, calcium or phosphate. Methods This was a randomized, double-blind, placebo-controlled trial with 1-year follow-up that enrolled dialysis patients with 25-hydroxy-vitamin D [25(OH)D] concentration <50 nmol/L. Consenting patients were randomized to 50 000 U/week oral cholecalciferol or matching placebo. Dosage was adjusted at 3- and 6-month study visits, targeting a 25(OH)D concentration >80 nmol/L. The primary objectives were to assess the effect of supplementation on renal-specific symptoms and on hand-grip strength. Symptoms were assessed using the Kidney Disease Quality of Life Short Form and muscle strength with a hand grip-strength dynamometer. Hypothesis testing was by two-group t-test and Wilcoxon rank-sum on an intention-to-treat basis. Results In all, 68 participants were randomized and received study medication. Median 12-month plasma 25(OH)D concentration was 119 nmol/L and 37 nmol/L in the cholecalciferol and placebo groups, respectively. There was no statistical difference in primary outcomes at 12 months. Mean symptom scores at 12 months were two lower in the cholecalciferol group (95% confidence interval −10 to 6) and geometric mean grip-strength was 27 kg in both groups. Symptoms, strength, BP, plasma mineral bone parameters and adverse events were not different between the groups at follow-up. Conclusions High-dose cholecalciferol in a deficient dialysis population had no effect on muscle strength or symptoms but appears safe. [ABSTRACT FROM AUTHOR]

Published
2019
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