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1,273 results on '"Buckley, Christopher D."'

1. A multi-omic atlas of human embryonic skeletal development

Author

To, Ken, Fei, Lijiang, Pett, J. Patrick, Roberts, Kenny, Blain, Raphael, Polański, Krzysztof, Li, Tong, Yayon, Nadav, He, Peng, Xu, Chuan, Cranley, James, Moy, Madelyn, Li, Ruoyan, Kanemaru, Kazumasa, Huang, Ni, Megas, Stathis, Richardson, Laura, Kapuge, Rakesh, Perera, Shani, Tuck, Elizabeth, Wilbrey-Clark, Anna, Mulas, Ilaria, Memi, Fani, Cakir, Batuhan, Predeus, Alexander V., Horsfall, David, Murray, Simon, Prete, Martin, Mazin, Pavel, He, Xiaoling, Meyer, Kerstin B., Haniffa, Muzlifah, Barker, Roger A., Bayraktar, Omer, Chédotal, Alain, Buckley, Christopher D., and Teichmann, Sarah A.

Published
2024
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3. A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease

Author

Thomas, Tom, Friedrich, Matthias, Rich-Griffin, Charlotte, Pohin, Mathilde, Agarwal, Devika, Pakpoor, Julia, Lee, Carl, Tandon, Ruchi, Rendek, Aniko, Aschenbrenner, Dominik, Jainarayanan, Ashwin, Voda, Alexandru, Siu, Jacqueline H. Y., Sanches-Peres, Raphael, Nee, Eloise, Sathananthan, Dharshan, Kotliar, Dylan, Todd, Peter, Kiourlappou, Maria, Gartner, Lisa, Ilott, Nicholas, Issa, Fadi, Hester, Joanna, Turner, Jason, Nayar, Saba, Mackerodt, Jonas, Zhang, Fan, Jonsson, Anna, Brenner, Michael, Raychaudhuri, Soumya, Kulicke, Ruth, Ramsdell, Danielle, Stransky, Nicolas, Pagliarini, Ray, Bielecki, Piotr, Spies, Noah, Marsden, Brian, Taylor, Stephen, Wagner, Allon, Klenerman, Paul, Walsh, Alissa, Coles, Mark, Jostins-Dean, Luke, Powrie, Fiona M., Filer, Andrew, Travis, Simon, Uhlig, Holm H., Dendrou, Calliope A., and Buckley, Christopher D.

Published
2024
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4. Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning

Author

Neag, Georgiana, Lewis, Jonathan, Turner, Jason D., Manning, Julia E., Dean, Isaac, Finlay, Melissa, Poologasundarampillai, Gowsihan, Woods, Jonathan, Sahu, Muhammad Arham, Khan, Kabir A., Begum, Jenefa, McGettrick, Helen M., Bellantuono, Ilaria, Heath, Victoria, Jones, Simon W., Buckley, Christopher D., Bicknell, Roy, and Naylor, Amy J.

Published
2024
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5. A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution

Author

Ng, Michael T. H., Borst, Rowie, Gacaferi, Hamez, Davidson, Sarah, Ackerman, Jessica E., Johnson, Peter A., Machado, Caio C., Reekie, Ian, Attar, Moustafa, Windell, Dylan, Kurowska-Stolarska, Mariola, MacDonald, Lucy, Alivernini, Stefano, Garvilles, Micon, Jansen, Kathrin, Bhalla, Ananya, Lee, Angela, Charlesworth, James, Chowdhury, Rajat, Klenerman, Paul, Powell, Kate, Hackstein, Carl-Philip, Furniss, Dominic, Rees, Jonathan, Gilroy, Derek, Coles, Mark, Carr, Andrew J., Sansom, Stephen N., Buckley, Christopher D., and Dakin, Stephanie G.

Published
2024
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8. CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis

Author

Rauber, Simon, Mohammadian, Hashem, Schmidkonz, Christian, Atzinger, Armin, Soare, Alina, Treutlein, Christoph, Kemble, Samuel, Mahony, Christopher B., Geisthoff, Manuel, Angeli, Mario R., Raimondo, Maria G., Xu, Cong, Yang, Kai-Ting, Lu, Le, Labinsky, Hannah, Saad, Mina S. A., Gwellem, Charles A., Chang, Jiyang, Huang, Kaiyue, Kampylafka, Eleni, Knitza, Johannes, Bilyy, Rostyslav, Distler, Jörg H. W., Hanlon, Megan M., Fearon, Ursula, Veale, Douglas J., Roemer, Frank W., Bäuerle, Tobias, Maric, Hans M., Maschauer, Simone, Ekici, Arif B., Buckley, Christopher D., Croft, Adam P., Kuwert, Torsten, Prante, Olaf, Cañete, Juan D., Schett, Georg, and Ramming, Andreas

Published
2024
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11. Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial

Author

Norton, Sam, Lempp, Heidi, Opena, Maria, Subesinghe, Sujith, Garrood, Toby, Menon, Bina, Ng, Nora, Douglas, Karen, Koutsianas, Christos, Cooles, Faye, Falahee, Marie, Echavez-Naguicnic, Irene, Bharadwaj, Anurag, Villaruel, Michael, Pande, Ira, Collins, David, Pegler, Suzannah, Raizada, Sabrina, Siebert, Stefan, Fragoulis, George, Guinto, Jesusa, Galloway, James, Rutherford, Andrew, Barnes, Theresa, Jeffrey, Helen, Patel, Yusuf, Batley, Michael, O'Reilly, Brendan, Venkatachalam, Srivinisan, Sheeran, Thomas, Gorman, Claire, Reynolds, Piero, Khan, Asad, Gullick, Nicola, Banerjee, Siwalik, Mankia, Kulveer, Jordan, Deepak, Rowlands, Jane, Starmans-Kool, Mirian, Taylor, James, Nandi, Pradip, Sahbudin, Ilfita, Maybury, Mark, Hider, Samantha, Barcroft, Ann, McNally, Jeremy, Kitchen, Jo, Nisar, Muhammad, Quick, Vanessa, Cope, Andrew P, Jasenecova, Marianna, Vasconcelos, Joana C, Filer, Andrew, Raza, Karim, Qureshi, Sumera, D'Agostino, Maria Antonietta, McInnes, Iain B, Isaacs, John D, Pratt, Arthur G, Fisher, Benjamin A, Buckley, Christopher D, Emery, Paul, Ho, Pauline, Buch, Maya H, Ciurtin, Coziana, van Schaardenburg, Dirkjan, Huizinga, Thomas, Toes, René, Georgiou, Evangelos, Kelly, Joanna, Murphy, Caroline, and Prevost, A Toby

Published
2024
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16. Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases

Author

Korsunsky, Ilya, Wei, Kevin, Pohin, Mathilde, Kim, Edy Y., Barone, Francesca, Major, Triin, Taylor, Emily, Ravindran, Rahul, Kemble, Samuel, Watts, Gerald F.M., Jonsson, A. Helena, Jeong, Yunju, Athar, Humra, Windell, Dylan, Kang, Joyce B., Friedrich, Matthias, Turner, Jason, Nayar, Saba, Fisher, Benjamin A., Raza, Karim, Marshall, Jennifer L., Croft, Adam P., Tamura, Tomoyoshi, Sholl, Lynette M., Vivero, Marina, Rosas, Ivan O., Bowman, Simon J., Coles, Mark, Frei, Andreas P., Lassen, Kara, Filer, Andrew, Powrie, Fiona, Buckley, Christopher D., Brenner, Michael B., and Raychaudhuri, Soumya

Published
2022
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17. Asparagine availability controls germinal center B cell homeostasis.

Author

Yazicioglu, Yavuz F., Marin, Eros, Andrew, Hana F., Bentkowska, Karolina, Johnstone, Julia C., Mitchell, Robert, Wong, Zhi Yi, Zec, Kristina, Fergusson, Joannah, Borsa, Mariana, Raza, Iwan G. A., Attar, Moustafa, Ali, Mohammad, Kronsteiner, Barbara, Furlani, Izadora L., MacRae, James I., Devine, Michael J., Coles, Mark, Buckley, Christopher D., and Dunachie, Susanna J.

Subjects
HUMORAL immunity, B cells, METABOLIC reprogramming, NUCLEOTIDE synthesis, GERMINAL centers
Abstract

The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we identified that asparagine (Asn) metabolism was highly up-regulated and essential for B cell function. Asparagine synthetase (ASNS) was up-regulated after B cell activation through the integrated stress response sensor GCN2. Conditional deletion of Asns in B cells impaired survival and proliferation in low Asn conditions. Removal of environmental Asn by asparaginase or dietary restriction compromised the GC reaction, impairing affinity maturation and the humoral response to influenza infection. Furthermore, metabolic adaptation to the absence of Asn required ASNS, and oxidative phosphorylation, mitochondrial homeostasis, and synthesis of nucleotides were particularly sensitive to Asn deprivation. These findings demonstrate that Asn metabolism acts as a key regulator of B cell function and GC homeostasis. Editor's summary: Germinal center B cells proliferate at an almost unparalleled rate, yet the metabolic pathways that fuel GC B cell proliferation are not fully understood. By metabolic profiling in murine GC B cells, Yazicioglu et al. identify that the amino acid asparagine (Asn) was up-regulated. Asn metabolism was required to regulate GC B cell metabolic homeostasis and GC function, including antibody affinity maturation and humoral immune response. When environmental Asn was limited, GC B cells used the enzyme asparagine synthetase (ASNS) for Asn production, which was up-regulated by the integrated stress response sensor GCN2. These findings implicate Asn metabolism in GC function and humoral immunity. —Hannah Isles [ABSTRACT FROM AUTHOR]

Published
2024
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18. Hexokinase 2 as a novel selective metabolic target for rheumatoid arthritis.

Author

Bustamante, Marta F, Oliveira, Patricia G, Garcia-Carbonell, Ricard, Croft, Adam P, Smith, Jeff M, Serrano, Ramon L, Sanchez-Lopez, Elsa, Liu, Xiao, Kisseleva, Tatiana, Hay, Nissim, Buckley, Christopher D, Firestein, Gary S, Murphy, Anne N, Miyamoto, Shigeki, and Guma, Monica

Subjects
Synovial Membrane, Animals, Mice, Transgenic, Humans, Arthritis, Experimental, Arthritis, Rheumatoid, Osteoarthritis, Synovitis, Hexokinase, RNA, Small Interfering, Inflammation Mediators, Cell Movement, Gene Expression Regulation, Synoviocytes, autoimmune diseases, fibroblasts, inflammation, rheumatoid arthritis, Autoimmune Disease, Aging, Arthritis, Aetiology, 2.1 Biological and endogenous factors, Musculoskeletal, Inflammatory and immune system, Clinical Sciences, Immunology, Public Health and Health Services, Arthritis & Rheumatology
Abstract

ObjectivesRecent studies indicate that glucose metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Hexokinases (HKs) catalyse the first step in glucose metabolism, and HK2 constitutes the principal HK inducible isoform. We hypothesise that HK2 contributes to the synovial lining hypertrophy and plays a critical role in bone and cartilage damage.MethodsHK1 and HK2 expression were determined in RA and osteoarthritis (OA) synovial tissue by immunohistochemistry. RA FLS were transfected with either HK1 or HK2 siRNA, or infected with either adenovirus (ad)-GFP, ad-HK1 or ad-HK2. FLS migration and invasion were assessed. To study the role of HK2 in vivo, 108 particles of ad-HK2 or ad-GFP were injected into the knee of wild-type mice. K/BxN serum transfer arthritis was induced in HK2F/F mice harbouring Col1a1-Cre (HK2Col1), to delete HK2 in non-haematopoietic cells.ResultsHK2 is particular of RA histopathology (9/9 RA; 1/8 OA) and colocalises with FLS markers. Silencing HK2 in RA FLS resulted in a less invasive and migratory phenotype. Consistently, overexpression of HK2 resulted in an increased ability to migrate and invade. It also increased extracellular lactate production. Intra-articular injection of ad-HK2 in normal knees dramatically increased synovial lining thickness, FLS activation and proliferation. HK2 was highly expressed in the synovial lining after K/BxN serum transfer arthritis. HK2Col1 mice significantly showed decreased arthritis severity, bone and cartilage damage.ConclusionHK2 is specifically expressed in RA synovial lining and regulates FLS aggressive functions. HK2 might be an attractive selective metabolic target safer than global glycolysis for RA treatment.

Published
2018

19. Immunofibroblasts regulate LTα3 expression in tertiary lymphoid structures in a pathway dependent on ICOS/ICOSL interaction

Author

Nayar, Saba, Pontarini, Elena, Campos, Joana, Berardicurti, Onorina, Smith, Charlotte G., Asam, Saba, Gardner, David H., Colafrancesco, Serena, Lucchesi, Davide, Coleby, Rachel, Chung, Ming-May, Iannizzotto, Valentina, Hunter, Kelly, Bowman, Simon J., Carlesso, Gianluca, Herbst, Ronald, McGettrick, Helen M., Browning, Jeff, Buckley, Christopher D., Fisher, Benjamin A., Bombardieri, Michele, and Barone, Francesca

Published
2022
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22. The complement system drives local inflammatory tissue priming by metabolic reprogramming of synovial fibroblasts

Author

Friščić, Jasna, Böttcher, Martin, Reinwald, Christiane, Bruns, Heiko, Wirth, Benjamin, Popp, Samantha-Josefine, Walker, Kellie Irene, Ackermann, Jochen A., Chen, Xi, Turner, Jason, Zhu, Honglin, Seyler, Lisa, Euler, Maximilien, Kirchner, Philipp, Krüger, René, Ekici, Arif B., Major, Triin, Aust, Oliver, Weidner, Daniela, Fischer, Anita, Andes, Fabian T., Stanojevic, Zeljka, Trajkovic, Vladimir, Herrmann, Martin, Korb-Pap, Adelheid, Wank, Isabel, Hess, Andreas, Winter, Johnathan, Wixler, Viktor, Distler, Jörg, Steiner, Günter, Kiener, Hans P., Frey, Benjamin, Kling, Lasse, Raza, Karim, Frey, Silke, Kleyer, Arnd, Bäuerle, Tobias, Hughes, Timothy R., Grüneboom, Anika, Steffen, Ulrike, Krönke, Gerhard, Croft, Adam P., Filer, Andrew, Köhl, Jörg, Klein, Kerstin, Buckley, Christopher D., Schett, Georg, Mougiakakos, Dimitrios, and Hoffmann, Markus H.

Published
2021
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24. The impact of autoantibodies against citrullinated, carbamylated, and acetylated peptides on radiographic progression in patients with new-onset rheumatoid arthritis: an observational cohort study

Author

De Bari, Cosimo, Duncan, Margaret, Fraser, Susan, Gray, Mohini, Hutton, Lisa, Harvie, John, Kumar, Vinod, McMahon, Mike, Munro, Robin, Larkin, John, McKay, Neil, McLaren, John, Ralston, Stuart, Reid, David M, Richmond, Ruth, Roberts, Gillian, Saunders, Sarah, Wilson, Hilary, Nijjar, Jagtar S, Morton, Fraser R, Bang, Holger, Buckley, Christopher D, van der Heijde, Désirée, Gilmour, Ashley, Paterson, Caron, McInnes, Iain B, Porter, Duncan, and Raza, Karim

Published
2021
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26. Functional analysis of fibroblasts and macrophages in head and neck paragangliomas.

Author

Baruah, Paramita, Marshall, Jennifer L., Nefla, Meriam, Pucino, Valentina, Adams, Holly, Turner, Jason D., Gilbert, Sebastian, Powell, Emily, Neag, Georgiana, Monksfield, Peter, Irving, Richard M., Croft, Adam P., Dumitriu, Ingrid E., and Buckley, Christopher D.

Subjects
FIBROBLASTS, STROMAL cells, INSULIN receptors, TUMOR microenvironment, MACROPHAGES
Abstract

Background and aim: Head and neck paragangliomas (HNPGN) are tumours that carry significant morbidity The role of the stroma in the pathogenesis of HNPGN is not completely understood. This study explores the profile of fibroblasts and macrophages in HNPGN. Methods: Ten patients undergoing HNPGN surgery were recruited. CD68 and CD163 immunohistochemistry was performed for macrophage analysis; CD90 and podoplanin (PDPN) expression was examined to identify fibroblasts. RT-qPCR was performed on HNPGN tissue for macrophage- and fibroblast-associated molecules. Fibroblast cultures were established from HNPGN were analysed by RT-qPCR and flowcytometry. Confocal microscopy for MCT1 and MCT4 was performed in HNPGN. Results: CD68 and CD163 expressing macrophages were noted in HNPGN. CD90 and PDPN expressing cells were present in HNPGN. RT-qPCR analysis showed expression of phenotypic and functional macrophage- and fibroblast-associated molecules in HNPGN. RT-qPCR analysis of fibroblasts cultured from HNPGN confirmed the expression of several molecules including PDPN at comparable levels to healthy tissue fibroblasts. Expression of FAP, MCT-1, insulin receptor (CD220) and insulin growth factor receptor-2 (CD222) was noted on HNPGN derived fibroblasts on flowcytometry. MCT1 and MCT4 were expressed in HNPGN tumour cells and stromal macrophages in-situ. Conclusion: Fibroblasts and macrophages are present in the HNPGN tumour microenvironment, and several macrophage and fibroblast functional markers are expressed in HNPGN. Macrophages in HNPGN tissue express metabolic markers MCT1 and MCT4. Further analysis of the fibroblast and macrophage function in HNPGN will improve our understanding of their potential roles in tumour pathogenesis. [ABSTRACT FROM AUTHOR]

Published
2024
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27. Efficacy, patient-reported outcomes, and safety of the anti-granulocyte macrophage colony-stimulating factor antibody otilimab (GSK3196165) in patients with rheumatoid arthritis: a randomised, phase 2b, dose-ranging study

Author

Buckley, Christopher D, Simón-Campos, Jesus A, Zhdan, Vyacheslav, Becker, Brandon, Davy, Katherine, Fisheleva, Elena, Gupta, Anubha, Hawkes, Carol, Inman, David, Layton, Mark, Mitchell, Nina, Patel, Jatin, Saurigny, Didier, Williamson, Russell, and Tak, Paul P

Published
2020
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30. Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology

Author

Nayar, Saba, Campos, Joana, Smith, Charlotte G., Iannizzotto, Valentina, Gardner, David H., Mourcin, Frédéric, Roulois, David, Turner, Jason, Sylvestre, Marvin, Asam, Saba, Glaysher, Bridget, Bowman, Simon J., Fearon, Douglas T., Filer, Andrew, Tarte, Karin, Luther, Sanjiv A., Fisher, Benjamin A., Buckley, Christopher D., Coles, Mark C., and Barone, Francesca

Published
2019

32. Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial

Author

Cope, Andrew P, Jasenecova, Marianna, Vasconcelos, Joana C, Filer, Andrew, Raza, Karim, Qureshi, Sumera, D'Agostino, Maria Antonietta, Mcinnes, Iain B, Isaacs, John D, Pratt, Arthur G, Fisher, Benjamin A, Buckley, Christopher D, Emery, Paul, Ho, Pauline, Buch, Maya H, Ciurtin, Coziana, van Schaardenburg, Dirkjan, Huizinga, Thoma, Toes, René, Georgiou, Evangelo, Kelly, Joanna, Murphy, Caroline, Prevost, A Toby, Norton, Sam, Lempp, Heidi, Opena, Maria, Subesinghe, Sujith, Garrood, Toby, Menon, Bina, Ng, Nora, Douglas, Karen, Koutsianas, Christo, Cooles, Faye, Falahee, Marie, Echavez-Naguicnic, Irene, Bharadwaj, Anurag, Villaruel, Michael, Pande, Ira, Collins, David, Pegler, Suzannah, Raizada, Sabrina, Siebert, Stefan, Fragoulis, George, Guinto, Jesusa, Galloway, Jame, Rutherford, Andrew, Barnes, Theresa, Jeffrey, Helen, Patel, Yusuf, Batley, Michael, O'Reilly, Brendan, Venkatachalam, Srivinisan, Sheeran, Thoma, Gorman, Claire, Reynolds, Piero, Khan, Asad, Gullick, Nicola, Banerjee, Siwalik, Mankia, Kulveer, Jordan, Deepak, Rowlands, Jane, Starmans-Kool, Mirian, Taylor, Jame, Nandi, Pradip, Sahbudin, Ilfita, Maybury, Mark, Hider, Samantha, Barcroft, Ann, Mcnally, Jeremy, Kitchen, Jo, Nisar, Muhammad, Quick, Vanessa, D'Agostino, Maria Antonietta (ORCID:0000-0002-5347-0060), Cope, Andrew P, Jasenecova, Marianna, Vasconcelos, Joana C, Filer, Andrew, Raza, Karim, Qureshi, Sumera, D'Agostino, Maria Antonietta, Mcinnes, Iain B, Isaacs, John D, Pratt, Arthur G, Fisher, Benjamin A, Buckley, Christopher D, Emery, Paul, Ho, Pauline, Buch, Maya H, Ciurtin, Coziana, van Schaardenburg, Dirkjan, Huizinga, Thoma, Toes, René, Georgiou, Evangelo, Kelly, Joanna, Murphy, Caroline, Prevost, A Toby, Norton, Sam, Lempp, Heidi, Opena, Maria, Subesinghe, Sujith, Garrood, Toby, Menon, Bina, Ng, Nora, Douglas, Karen, Koutsianas, Christo, Cooles, Faye, Falahee, Marie, Echavez-Naguicnic, Irene, Bharadwaj, Anurag, Villaruel, Michael, Pande, Ira, Collins, David, Pegler, Suzannah, Raizada, Sabrina, Siebert, Stefan, Fragoulis, George, Guinto, Jesusa, Galloway, Jame, Rutherford, Andrew, Barnes, Theresa, Jeffrey, Helen, Patel, Yusuf, Batley, Michael, O'Reilly, Brendan, Venkatachalam, Srivinisan, Sheeran, Thoma, Gorman, Claire, Reynolds, Piero, Khan, Asad, Gullick, Nicola, Banerjee, Siwalik, Mankia, Kulveer, Jordan, Deepak, Rowlands, Jane, Starmans-Kool, Mirian, Taylor, Jame, Nandi, Pradip, Sahbudin, Ilfita, Maybury, Mark, Hider, Samantha, Barcroft, Ann, Mcnally, Jeremy, Kitchen, Jo, Nisar, Muhammad, Quick, Vanessa, and D'Agostino, Maria Antonietta (ORCID:0000-0002-5347-0060)

Abstract

Background: Individuals with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor, and symptoms, such as inflammatory joint pain, are at high risk of developing rheumatoid arthritis. In the arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept (APIPPRA) trial, we aimed to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with the T-cell co-stimulation modulator abatacept. Methods: The APIPPRA study was a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial done in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands. Participants (aged ≥18 years) at risk of rheumatoid arthritis positive for ACPA and rheumatoid factor with inflammatory joint pain were recruited. Exclusion criteria included previous episodes of clinical synovitis and previous use of corticosteroids or disease-modifying antirheumatic drugs. Participants were randomly assigned (1:1) using a computer-generated permuted block randomisation (block sizes of 2 and 4) stratified by sex, smoking, and country, to 125 mg abatacept subcutaneous injections weekly or placebo for 12 months, and then followed up for 12 months. Masking was achieved by providing four kits (identical in appearance and packaging) with pre-filled syringes with coded labels of abatacept or placebo every 3 months. The primary endpoint was the time to development of clinical synovitis in three or more joints or rheumatoid arthritis according to American College of Rheumatology and European Alliance of Associations for Rheumatology 2010 criteria, whichever was met first. Synovitis was confirmed by ultrasonography. Follow-up was completed on Jan 13, 2021. All participants meeting the intention-to-treat principle were included in the analysis. This trial was registered with EudraCT (2013-003413-18). Findings: Between Dec 22, 2014, and Jan 14, 2019, 280 individuals were evaluated for el

Published
2024

33. Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis

Author

Alivernini, Stefano, MacDonald, Lucy, Elmesmari, Aziza, Finlay, Samuel, Tolusso, Barbara, Gigante, Maria Rita, Petricca, Luca, Di Mario, Clara, Bui, Laura, Perniola, Simone, Attar, Moustafa, Gessi, Marco, Fedele, Anna Laura, Chilaka, Sabarinadh, Somma, Domenico, Sansom, Stephen N., Filer, Andrew, McSharry, Charles, Millar, Neal L., Kirschner, Kristina, Nerviani, Alessandra, Lewis, Myles J., Pitzalis, Costantino, Clark, Andrew R., Ferraccioli, Gianfranco, Udalova, Irina, Buckley, Christopher D., Gremese, Elisa, McInnes, Iain B., Otto, Thomas D., and Kurowska-Stolarska, Mariola

Published
2020
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36. BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (the BIO-FLARE study): protocol for a non-randomised longitudinal cohort study

Author

Rayner, Fiona, Anderson, Amy E., Baker, Kenneth F., Buckley, Christopher D., Dyke, Bernard, Fenton, Sally, Filer, Andrew, Goodyear, Carl S., Hilkens, Catharien M. U., Hiu, Shaun, Kerrigan, Sean, Kurowska-Stolarska, Mariola, Matthews, Fiona, McInnes, Iain, Ng, Wan-Fai, Pratt, Arthur G., Prichard, Jonathan, Raza, Karim, Siebert, Stefan, Stocken, Deborah, Teare, M. Dawn, Young, Stephen, and Isaacs, John D.

Published
2021
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38. Molecular Portraits of Early Rheumatoid Arthritis Identify Clinical and Treatment Response Phenotypes

Author

Lewis, Myles J., Barnes, Michael R., Blighe, Kevin, Goldmann, Katriona, Rana, Sharmila, Hackney, Jason A., Ramamoorthi, Nandhini, John, Christopher R., Watson, David S., Kummerfeld, Sarah K., Hands, Rebecca, Riahi, Sudeh, Rocher-Ros, Vidalba, Rivellese, Felice, Humby, Frances, Kelly, Stephen, Bombardieri, Michele, Ng, Nora, DiCicco, Maria, van der Heijde, Désirée, Landewé, Robert, van der Helm-van Mil, Annette, Cauli, Alberto, McInnes, Iain B., Buckley, Christopher D., Choy, Ernest, Taylor, Peter C., Townsend, Michael J., and Pitzalis, Costantino

Published
2019
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40. Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial

Author

Cope, Andrew P, primary, Jasenecova, Marianna, additional, Vasconcelos, Joana C, additional, Filer, Andrew, additional, Raza, Karim, additional, Qureshi, Sumera, additional, D'Agostino, Maria Antonietta, additional, McInnes, Iain B, additional, Isaacs, John D, additional, Pratt, Arthur G, additional, Fisher, Benjamin A, additional, Buckley, Christopher D, additional, Emery, Paul, additional, Ho, Pauline, additional, Buch, Maya H, additional, Ciurtin, Coziana, additional, van Schaardenburg, Dirkjan, additional, Huizinga, Thomas, additional, Toes, René, additional, Georgiou, Evangelos, additional, Kelly, Joanna, additional, Murphy, Caroline, additional, Prevost, A Toby, additional, Norton, Sam, additional, Lempp, Heidi, additional, Opena, Maria, additional, Subesinghe, Sujith, additional, Garrood, Toby, additional, Menon, Bina, additional, Ng, Nora, additional, Douglas, Karen, additional, Koutsianas, Christos, additional, Cooles, Faye, additional, Falahee, Marie, additional, Echavez-Naguicnic, Irene, additional, Bharadwaj, Anurag, additional, Villaruel, Michael, additional, Pande, Ira, additional, Collins, David, additional, Pegler, Suzannah, additional, Raizada, Sabrina, additional, Siebert, Stefan, additional, Fragoulis, George, additional, Guinto, Jesusa, additional, Galloway, James, additional, Rutherford, Andrew, additional, Barnes, Theresa, additional, Jeffrey, Helen, additional, Patel, Yusuf, additional, Batley, Michael, additional, O'Reilly, Brendan, additional, Venkatachalam, Srivinisan, additional, Sheeran, Thomas, additional, Gorman, Claire, additional, Reynolds, Piero, additional, Khan, Asad, additional, Gullick, Nicola, additional, Banerjee, Siwalik, additional, Mankia, Kulveer, additional, Jordan, Deepak, additional, Rowlands, Jane, additional, Starmans-Kool, Mirian, additional, Taylor, James, additional, Nandi, Pradip, additional, Sahbudin, Ilfita, additional, Maybury, Mark, additional, Hider, Samantha, additional, Barcroft, Ann, additional, McNally, Jeremy, additional, Kitchen, Jo, additional, Nisar, Muhammad, additional, and Quick, Vanessa, additional

Published
2024
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41. Automated multi-scale computational pathotyping (AMSCP) of inflamed synovial tissue.

Author

Bell, Richard D., Brendel, Matthew, Konnaris, Maxwell A., Xiang, Justin, Otero, Miguel, Fontana, Mark A., Bai, Zilong, Albrecht, Jennifer, Apruzzese, William, Boyce, Brendan F., Boyle, David L., Brenner, Michael B., Bridges Jr., S. Louis, Buckley, Christopher D., Buckner, Jane H., Bykerk, Vivian P., Dolan, James, Eisenhaure, Thomas M., Filer, Andrew, and Firestein, Gary S.

Subjects
RHEUMATOID arthritis, MEDICAL research, PHENOTYPES, HISTOPATHOLOGY, ARTHRITIS
Abstract

Rheumatoid arthritis (RA) is a complex immune-mediated inflammatory disorder in which patients suffer from inflammatory-erosive arthritis. Recent advances on histopathology heterogeneity of RA synovial tissue revealed three distinct phenotypes based on cellular composition (pauci-immune, diffuse and lymphoid), suggesting that distinct etiologies warrant specific targeted therapy which motivates a need for cost effective phenotyping tools in preclinical and clinical settings. To this end, we developed an automated multi-scale computational pathotyping (AMSCP) pipeline for both human and mouse synovial tissue with two distinct components that can be leveraged together or independently: (1) segmentation of different tissue types to characterize tissue-level changes, and (2) cell type classification within each tissue compartment that assesses change across disease states. Here, we demonstrate the efficacy, efficiency, and robustness of the AMSCP pipeline as well as the ability to discover novel phenotypes. Taken together, we find AMSCP to be a valuable cost-effective method for both pre-clinical and clinical research. Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis. [ABSTRACT FROM AUTHOR]

Published
2024
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43. Differential Expression of CD148 on leucocyte subsets in inflammatory arthritis

Author

Dave, Richa K, Naylor, Amy J, Young, Stephen P, Bayley, Rachel, Hardie, Debbie L, Haworth, Oliver, Rider, David A, Cook, Andrew D, Buckley, Christopher D, and Kellie, Stuart

Abstract

Abstract Introduction Monocytic cells play a central role in the aetiology of rheumatoid arthritis, and manipulation of the activation of these cells is an approach currently under investigation to discover new therapies for this and associated diseases. CD148 is a transmembrane tyrosine phosphatase that is highly expressed in monocytes and macrophages and, since this family of molecules plays an important role in the regulation of cell activity, CD148 is a potential target for the manipulation of macrophage activation. For any molecule to be considered a therapeutic target, it is important for it to be increased in activity or expression during disease. Methods We have investigated the expression of CD148 in two murine models of arthritis and in joints from rheumatoid arthritis (RA) patients using real-time PCR, immunohistochemistry, and studied the effects of proinflammatory stimuli on CD148 activity using biochemical assays. Results We report that CD148 mRNA is upregulated in diseased joints of mice with collagen-induced arthritis. Furthermore, we report that in mice CD148 protein is highly expressed in infiltrating monocytes of diseased joints, with a small fraction of T cells also expressing CD148. In human arthritic joints both T cells and monocytes expressed high levels of CD148, however, we show differential expression of CD148 in T cells and monocytes from normal human peripheral blood compared to peripheral blood from RA and both normal and RA synovial fluid. Finally, we show that synovial fluid from rheumatoid arthritis patients suppresses CD148 phosphatase activity. Conclusions CD148 is upregulated in macrophages and T cells in human RA samples, and its activity is enhanced by treatment with tumour necrosis factor alpha (TNFα), and reduced by synovial fluid or oxidising conditions. A greater understanding of the role of CD148 in chronic inflammation may lead to alternative therapeutic approaches to these diseases.

Published
2013

44. Distinct fibroblast subsets drive inflammation and damage in arthritis

Author

Croft, Adam P., Campos, Joana, Jansen, Kathrin, Turner, Jason D., Marshall, Jennifer, Attar, Moustafa, Savary, Loriane, Wehmeyer, Corinna, Naylor, Amy J., Kemble, Samuel, Begum, Jenefa, Dürholz, Kerstin, Perlman, Harris, Barone, Francesca, McGettrick, Helen M., Fearon, Douglas T., Wei, Kevin, Raychaudhuri, Soumya, Korsunsky, Ilya, Brenner, Michael B., Coles, Mark, Sansom, Stephen N., Filer, Andrew, and Buckley, Christopher D.

Published
2019
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45. Inflammatory regulation of glucocorticoid metabolism in mesenchymal stromal cells

Author

Ahasan, Mohammad M, Hardy, Rowan, Jones, Christopher, Kaur, Kirren, Nanus, Dominika, Juarez, Maria, Morgan, Stuart A, Hassan‐Smith, Zaki, Bénézech, Cécile, Caamaño, Jorge H, Hewison, Martin, Lavery, Gareth, Rabbitt, Elizabeth H, Clark, Andrew R, Filer, Andrew, Buckley, Christopher D, Raza, Karim, Stewart, Paul M, and Cooper, Mark S

Subjects
Genetics, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, Aetiology, Inflammatory and immune system, Cancer, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Animals, Arthritis, Rheumatoid, Cells, Cultured, Cytokines, Fibroblasts, Glucocorticoids, Humans, Inflammation, Interleukin-1beta, Mesenchymal Stem Cells, Mice, NF-kappa B, Osteoarthritis, Synovial Membrane, Clinical Sciences, Immunology, Public Health and Health Services, Arthritis & Rheumatology
Abstract

ObjectiveTissue glucocorticoid (GC) levels are regulated by the GC-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). This enzyme is expressed in cells and tissues arising from mesenchymal stromal cells. Proinflammatory cytokines dramatically increase expression of 11β-HSD1 in stromal cells, an effect that has been implicated in inflammatory arthritis, osteoporosis, obesity, and myopathy. Additionally, GCs act synergistically with proinflammatory cytokines to further increase enzyme expression. The present study was undertaken to investigate the mechanisms underlying this regulation.MethodsGene reporter analysis, rapid amplification of complementary DNA ends (RACE), chemical inhibition experiments, and genetic disruption of intracellular signaling pathways in mouse embryonic fibroblasts (MEFs) were used to define the molecular mechanisms underlying the regulation of 11β-HSD1 expression.ResultsGene reporter, RACE, and chemical inhibitor studies demonstrated that the increase in 11β-HSD1 expression with tumor necrosis factor α (TNFα)/interleukin-1β (IL-1β) occurred via the proximal HSD11B1 gene promoter and depended on NF-κB signaling. These findings were confirmed using MEFs with targeted disruption of NF-κB signaling, in which RelA (p65) deletion prevented TNFα/IL-1β induction of 11β-HSD1. GC treatment did not prevent TNFα-induced NF-κB nuclear translocation. The synergistic enhancement of TNFα-induced 11β-HSD1 expression with GCs was reproduced by specific inhibitors of p38 MAPK. Inhibitor and gene deletion studies indicated that the effects of GCs on p38 MAPK activity occurred primarily through induction of dual-specificity phosphatase 1 expression.ConclusionThe mechanism by which stromal cell expression of 11β-HSD1 is regulated is novel and distinct from that in other tissues. These findings open new opportunities for development of therapeutic interventions aimed at inhibiting or stimulating local GC levels in cells of mesenchymal stromal lineage during inflammation.

Published
2012

47. Differential expression, function and response to inflammatory stimuli of 11beta-hydroxysteroid dehydrogenase type 1 in human fibroblasts: a mechanism for tissue-specific regulation of inflammation.

Author

Hardy, Rowan S, Filer, Andrew, Cooper, Mark S, Parsonage, Greg, Raza, Karim, Hardie, Debbie L, Rabbitt, Elizabeth H, Stewart, Paul M, Buckley, Christopher D, and Hewison, Martin

Subjects
Synovial Membrane, Cells, Cultured, Fibroblasts, Bone Marrow, Skin, Humans, Arthritis, Rheumatoid, Osteoarthritis, Cortisone, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Tumor Necrosis Factor-alpha, RNA, Messenger, Interleukin-6, Glucocorticoids, Interleukin-1beta, Cells, Cultured, Arthritis, Rheumatoid, RNA, Messenger, Clinical Sciences, Immunology, Public Health and Health Services, Arthritis & Rheumatology
Abstract

Stromal cells such as fibroblasts play an important role in defining tissue-specific responses during the resolution of inflammation. We hypothesized that this involves tissue-specific regulation of glucocorticoids, mediated via differential regulation of the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). Expression, activity and function of 11beta-HSD1 was assessed in matched fibroblasts derived from various tissues (synovium, bone marrow and skin) obtained from patients with rheumatoid arthritis or osteoarthritis. 11beta-HSD1 was expressed in fibroblasts from all tissues but mRNA levels and enzyme activity were higher in synovial fibroblasts (2-fold and 13-fold higher mRNA levels in dermal and synovial fibroblasts, respectively, relative to bone marrow). Expression and activity of the enzyme increased in all fibroblasts following treatment with tumour necrosis factor-alpha or IL-1beta (bone marrow: 8-fold and 37-fold, respectively, compared to vehicle; dermal fibroblasts: 4-fold and 14-fold; synovial fibroblasts: 7-fold and 31-fold; all P < 0.01 compared with vehicle). Treatment with IL-4 or interferon-gamma was without effect, and there was no difference in 11beta-HSD1 expression between fibroblasts (from any site) obtained from patients with rheumatoid arthritis or osteoarthritis. In the presence of 100 nmol/l cortisone, IL-6 production--a characteristic feature of synovial derived fibroblasts--was significantly reduced in synovial but not dermal or bone marrow fibroblasts. This was prevented by co-treatment with an 11beta-HSD inhibitor, emphasizing the potential for autocrine activation of glucocorticoids in synovial fibroblasts. These data indicate that differences in fibroblast-derived glucocorticoid production (via the enzyme 11beta-HSD1) between cells from distinct anatomical locations may play a key role in the predeliction of certain tissues to develop persistent inflammation.

Published
2006

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