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4. Data from Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients

Author

Samson, Adel, primary, West, Emma J., primary, Carmichael, Jonathan, primary, Scott, Karen J., primary, Turnbull, Samantha, primary, Kuszlewicz, Bethany, primary, Dave, Rajiv V., primary, Peckham-Cooper, Adam, primary, Tidswell, Emma, primary, Kingston, Jennifer, primary, Johnpulle, Michelle, primary, da Silva, Barbara, primary, Jennings, Victoria A., primary, Bendjama, Kaidre, primary, Stojkowitz, Nicolas, primary, Lusky, Monika, primary, Prasad, K.R., primary, Toogood, Giles J., primary, Auer, Rebecca, primary, Bell, John, primary, Twelves, Chris J., primary, Harrington, Kevin J., primary, Vile, Richard G., primary, Pandha, Hardev, primary, Errington-Mais, Fiona, primary, Ralph, Christy, primary, Newton, Darren J., primary, Anthoney, Alan, primary, Melcher, Alan A., primary, and Collinson, Fiona, primary

Published
2023
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5. Supplementary Data from Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients

Author

Samson, Adel, primary, West, Emma J., primary, Carmichael, Jonathan, primary, Scott, Karen J., primary, Turnbull, Samantha, primary, Kuszlewicz, Bethany, primary, Dave, Rajiv V., primary, Peckham-Cooper, Adam, primary, Tidswell, Emma, primary, Kingston, Jennifer, primary, Johnpulle, Michelle, primary, da Silva, Barbara, primary, Jennings, Victoria A., primary, Bendjama, Kaidre, primary, Stojkowitz, Nicolas, primary, Lusky, Monika, primary, Prasad, K.R., primary, Toogood, Giles J., primary, Auer, Rebecca, primary, Bell, John, primary, Twelves, Chris J., primary, Harrington, Kevin J., primary, Vile, Richard G., primary, Pandha, Hardev, primary, Errington-Mais, Fiona, primary, Ralph, Christy, primary, Newton, Darren J., primary, Anthoney, Alan, primary, Melcher, Alan A., primary, and Collinson, Fiona, primary

Published
2023
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6. Supplementary Figure from Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients

Author

Samson, Adel, primary, West, Emma J., primary, Carmichael, Jonathan, primary, Scott, Karen J., primary, Turnbull, Samantha, primary, Kuszlewicz, Bethany, primary, Dave, Rajiv V., primary, Peckham-Cooper, Adam, primary, Tidswell, Emma, primary, Kingston, Jennifer, primary, Johnpulle, Michelle, primary, da Silva, Barbara, primary, Jennings, Victoria A., primary, Bendjama, Kaidre, primary, Stojkowitz, Nicolas, primary, Lusky, Monika, primary, Prasad, K.R., primary, Toogood, Giles J., primary, Auer, Rebecca, primary, Bell, John, primary, Twelves, Chris J., primary, Harrington, Kevin J., primary, Vile, Richard G., primary, Pandha, Hardev, primary, Errington-Mais, Fiona, primary, Ralph, Christy, primary, Newton, Darren J., primary, Anthoney, Alan, primary, Melcher, Alan A., primary, and Collinson, Fiona, primary

Published
2023
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7. Characterization of Blood Mucosal‐Associated Invariant T Cells in Patients With Axial Spondyloarthritis and of Resident Mucosal‐Associated Invariant T Cells From the Axial Entheses of Non‐Axial Spondyloarthritis Control Patients

Author

Rosine, Nicolas, primary, Rowe, Hannah, additional, Koturan, Surya, additional, Yahia‐Cherbal, Hanane, additional, Leloup, Claire, additional, Watad, Abdulla, additional, Berenbaum, Francis, additional, Sellam, Jeremie, additional, Dougados, Maxime, additional, Aimanianda, Vishukumar, additional, Cuthbert, Richard, additional, Bridgewood, Charlie, additional, Newton, Darren, additional, Bianchi, Elisabetta, additional, Rogge, Lars, additional, McGonagle, Dennis, additional, and Miceli‐Richard, Corinne, additional

Published
2022
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9. COVID-19 vaccination antibody responses in patients with aplastic anaemia and paroxysmal nocturnal haemoglobinuria

Author

Pike, Alexandra, primary, McKinley, Claire, additional, Forrest, Briony, additional, Scott, Rebecca, additional, Charlton, Emily, additional, Scott, Emma, additional, Zhakata, Tapiwa, additional, Harland, Mark, additional, Clarke, Deborah, additional, Davies, John R, additional, Toogood, Aurora, additional, Houghton, Nicola, additional, Youngs, Nora, additional, Barnfield, Catherine, additional, Richards, Stephen, additional, Payne, Daniel, additional, Arnold, Louise, additional, Munir, Tahla, additional, Muus, Petra, additional, Griffin, Morag, additional, Kelly, Richard J, additional, Hillmen, Peter, additional, and Newton, Darren, additional

Published
2022
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11. Characterization of Blood Mucosal Associated Invariant T ( MAIT ) cells in Axial Spondyloarthritis and of resident MAITs from control axial enthesis

Author

Rosine, Nicolas, Rowe, Hannah, Koturan, Surya, Yahia‐cherbal, Hanane, Leloup, Claire, Watad, Abdulla, Berenbaum, Francis, Sellam, Jeremie, Dougados, Maxime, Aimanianda, Vishukumar, Cuthbert, Richard, Bridgewood, Charlie, Newton, Darren, Bianchi, Elisabetta, Rogge, Lars, Mcgonagle, Dennis, Miceli‐richard, Corinne, Immunorégulation - Immunoregulation, Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), University of Leeds, Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Institut Pasteur [Paris] (IP), DMG is funded by the Leeds NIHR Biomedical Research Centre. Novartis UK Investigator Initiated non-clinical research funding support (HR, CB). AW was funded by the Celgene supported PARTNER fellowship program. Research funded by a Pfizer investigator initiated research grant (RJC) NR was funded by a Poste d’Accueil APHP and a grant fromSociété Française de Rhumatologie. This study was supported by grants from MSD Avenir (Project iCARE-SpA), a Sanofi Innovation award Europe, FOREUM Foundation for Research in Rheumatology, and from the Société Française de Rhumatologie., and Kop, Marie-Luce

Subjects
IL-17F, MAITs, [SDV.IMM] Life Sciences [q-bio]/Immunology, IL-17A, [SDV.IMM]Life Sciences [q-bio]/Immunology, axial spondyloarthritis, IL-17 producing cells
Abstract

International audience; ObjectivesThe importance of IL-17A in the pathogenesis of Axial Spondyloarthritis (AxSpA) has been demonstrated by the success of IL-17A blockade. However, the nature of the cell populations producing this important pro-inflammatory cytokine remains poorly defined. Accordingly, we characterized major IL-17A-producing blood cell populations in AxSpA, with reference to entheseal biology, with a focus on mucosal associated invariant T-cells, (MAITs) a population known to be capable of producing IL-17.MethodsIL-17A production from 5 sorted peripheral blood cell populations, namely MAITs, γδ T-cells, CD4+T-cells, CD8+T-cells and neutrophils was evaluated pre- and post-stimulation with PMA, the calcium ionophore A23187 and β1,3 glucan. IL-17A transcript and protein expression were determined using nCounter Technology and ultra-sensitive SimoA technology, respectively. MAITs from control human axial entheses (n=5) were further characterized by flow cytometric immunophenotyping, qPCR and IL-17 production assessed following stimulation.ResultsIn blood, on a per cell basis, MAIT cells produced the highest amount of IL-17A compared to CD4+ (p

Published
2022
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12. Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients

Author

Samson, Adel, primary, West, Emma J., additional, Carmichael, Jonathan, additional, Scott, Karen J., additional, Turnbull, Samantha, additional, Kuszlewicz, Bethany, additional, Dave, Rajiv V., additional, Peckham-Cooper, Adam, additional, Tidswell, Emma, additional, Kingston, Jennifer, additional, Johnpulle, Michelle, additional, da Silva, Barbara, additional, Jennings, Victoria A., additional, Bendjama, Kaidre, additional, Stojkowitz, Nicolas, additional, Lusky, Monika, additional, Prasad, K.R., additional, Toogood, Giles J., additional, Auer, Rebecca, additional, Bell, John, additional, Twelves, Chris J., additional, Harrington, Kevin J., additional, Vile, Richard G., additional, Pandha, Hardev, additional, Errington-Mais, Fiona, additional, Ralph, Christy, additional, Newton, Darren J., additional, Anthoney, Alan, additional, Melcher, Alan A., additional, and Collinson, Fiona, additional

Published
2022
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13. Effectiveness of SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on DMARDs: as determined by antibody and T cell responses

Author

Saleem, Benazir, primary, Ross, Rebecca L, additional, Bissell, Lesley-Anne, additional, Aslam, Aamir, additional, Mankia, Kulveer, additional, Duquenne, Laurence, additional, Corsadden, Diane, additional, Carter, Clive, additional, Hughes, Pam, additional, Nadat, Fatima A, additional, Mulipa, Panji, additional, Lobb, Mark, additional, Clarke, Brendan, additional, Mbara, Katie, additional, Morton, Ruth, additional, Dibb, Sophie, additional, Chowdhury, Rahaymin, additional, Newton, Darren, additional, Pike, Alexandra, additional, Kakkar, Vishal, additional, Savic, Sinisia, additional, DelGaldo, Francesco, additional, and Emery, Paul, additional

Published
2022
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14. COVID-19 Vaccination Responses in Patients With Aplastic Anaemia and Paroxysmal Nocturnal Haemoglobinuria; Results From the UK (Leeds) PNH National Service Prospective Study

Author

Pike, Alexandra, primary, McKinley, Claire, additional, Forrest, Briony, additional, Scott, Rebecca, additional, Charlton, Emily, additional, Scott, Emma, additional, Zhakata, Tapiwa, additional, Harland, Mark, additional, Clarke, Deborah, additional, Toogood, Aurora, additional, Houghton, Nicola, additional, Youngs, Nora, additional, Barnfield, Catherine, additional, Richards, Stephen, additional, Payne, Daniel, additional, Arnold, Louise, additional, Munir, Tahla, additional, Muus, Petra, additional, Griffin, Morag, additional, Kelly, Richard, additional, Hillmen, Peter, additional, and Newton, Darren, additional

Published
2022
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16. The incidence and prevalence of patients with paroxysmal nocturnal haemoglobinuria and aplastic anaemia PNH syndrome : a retrospective analysis of the UK’s population-based haematological malignancy research network 2004-2018

Author

Richards, Stephen J., Painter, Daniel, Dickinson, Anita J., Griffin, Morag, Munir, Talha, Arnold, Louise, Payne, Daniel, Pike, Alexandra, Muus, Petra, Hill, Anita, Newton, Darren J., McKinley, Claire, Jones, Rachael, Kelly, Richard, Smith, Alexandra Gwen, Roman, Eve, and Hillmen, Peter

Subjects
hemic and lymphatic diseases
Abstract

Objectives A retrospective population-based study to determine the incidence and prevalence of patients with the rare blood disease paroxysmal nocturnal haemoglobinuria (PNH). Methods All patients were identified by flow cytometric detection of blood cells deficient in glycosylphosphatidylinositol (GPI) linked proteins at a single diagnostic reference laboratory that serves the Yorkshire based, Haematological Malignancy Research Network (HMRN) with a population of 3.8 million. Results One hundred and ninety-seven patients with detectable PNH clones at a level of >0.01% in at least two lineages of cells (neutrophils, monocytes and/or red cells) were identified over a 15-year period (2004-2018). Of these, 88% had aplastic anaemia (AA), 8% classical PNH and 3% myelodysplastic syndrome. The overall incidence rate was estimated at 0.35 cases per 100 000 people per year. This equates to 220 cases newly diagnosed in the United Kingdom each year. The overall prevalence rate was 3.81 per 100 000, this equates to an estimated 2400 prevalent cases in the UK. The overall and relative 5-year survival rates were 72% and 82.7%, respectively. Conclusions This study showed that classical haemolytic PNH is a rare disease and represents only a small proportion overall of patients with detectable PNH cells, the majority of which have aplastic anaemia.

Published
2021

17. Sars-Cov-2 Antibody and T-Cell Responses in Patients with Paroxysmal Nocturnal Hemoglobinuria and Aplastic Anemia after Four COVID-19 Vaccinations

Author

Pike, Alexandra, Fox, Natalie, McKinley, Claire E, Arnold, Louise M, Harland, Mark, Clarke, Deborah, Forrest, Briony, Houghton, Nicola, Youngs, Nora, Charlton, Emily, Zhakata, Tapiwa, Barnfield, Catherine, Harvey, Ruth, Wu, Mary, Kavanagh, Caitlin, Richards, Stephen John, Payne, Daniel, Varghese, Abraham Mullasseril, Nagumantry, Sateesh, Munir, Talha, Muus, Petra, Griffin, Morag, Newton, Darren, Hillmen, Peter, and Kelly, Richard J

Published
2023
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18. Ibrutinib and Rituximab Versus Fludarabine, Cyclophosphamide, and Rituximab for Patients in NCRI FLAIR Study with Previously Untreated CLL: Assessment of Mutational Landscape of Patients at Baseline and Prognostic Impact

Author

Dalal, Surita, Sarma, Anita, Shingles, Jane, Glover, Paul, Warren, Helen, Grand, Thomas, Webster, Nichola, Rawstron, Andy, Newton, Darren, Bell, Sue, Cairns, David Allan, Girvan, Sean, Greatorex, Natasha, Hockaday, Anna, Jackson, Sharon, Phillips, David, Stones, David, Allsup, David, Bloor, Adrian John Clifton, Varghese, Abraham Mullasseril, Munir, Talha, and Hillmen, Peter

Published
2023
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19. Molecular Analysis at Relapse of Patients Treated on the Ibrutinib and Rituximab Arm of the National Multi-Centre Phase III FLAIR Study in Previously Untreated CLL Patients

Author

Sarma, Anita, Evans, Charlotte, Dalal, Surita, Webster, Nichola, Rawstron, Andy, Shingles, Jane, Newton, Darren, Cairns, David Allan, Glover, Paul, Grand, Thomas, Warren, Helen, Bell, Sue, Girvan, Sean, Greatorex, Natasha, Hockaday, Anna, Jackson, Sharon, Phillips, David, Stones, David, Allsup, David, Bloor, Adrian John Clifton, Varghese, Abraham Mullasseril, Munir, Talha, and Hillmen, Peter

Published
2023
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22. The incidence and prevalence of patients with paroxysmal nocturnal haemoglobinuria and aplastic anaemia PNH syndrome: A retrospective analysis of the UK’s population‐based haematological malignancy research network 2004‐2018

Author

Richards, Stephen J., primary, Painter, Daniel, additional, Dickinson, Anita J., additional, Griffin, Morag, additional, Munir, Talha, additional, Arnold, Louise, additional, Payne, Daniel, additional, Pike, Alexandra, additional, Muus, Petra, additional, Hill, Anita, additional, Newton, Darren J., additional, McKinley, Claire, additional, Jones, Rachael, additional, Kelly, Richard, additional, Smith, Alex, additional, Roman, Eve, additional, and Hillmen, Peter, additional

Published
2021
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23. Immunophenotypic assessment of PNHclones in major and minor cell lineages in the peripheral blood of patients with paroxysmal nocturnal hemoglobinuria

Author

Richards, Stephen J., Dickinson, Anita J., Newton, Darren J., and Hillmen, Peter

Abstract

Flow cytometric immunophenotyping is essential for the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). Most cases have easy to interpret flow cytometry profiles with red cells, neutrophils and monocytes showing complete deficiency of glycophosphatidylinositol (GPI) linked antigen expression. Some cases are more challenging to interpret due to the presence of multiple populations of PNH cells and variable levels of GPI antigen expression. We studied 46 known PNH patients, many with complex immunophenotypic profiles using a novel, single tube, multi‐parameter 7‐color immunophenotyping assay that allowed simultaneous detection and assessment of PNH clones within multiple lineages of peripheral blood leucocytes. Red cell PNH clones were also assessed in total and immature (CD71+) components by CD59 expression. For individual patients, total PNH clones in each cell lineage were highly correlated. Monocytes, eosinophils and basophils showed the highest proportions of PNH cells. Red cell PNH clones were typically smaller than monocyte and neutrophil PNH clones. In most cases, PNH clones were detectable in minor leucocyte populations where multiple populations of PNH cells were present, variability in the proportions of type II and type III cells was seen across different cell lineages, even though total PNH clones remained similar. This study shows that PNH patients with multiple PNH clones do not always display the same abnormality across all cell lineages routinely tested. There is no simple explanation for this but is likely due to a combination of complex molecular, genetic and biochemical dysfunction in different blood cell types.

Published
2022
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25. MCP-1 but not CINC synthesis is increased in rat pancreatic acini in response to cerulein hyperstimulation

Author

Bhatia, Madhav, Brady, Mark, Kang, Yun Kyung, Costello, Eithne, Newton, Darren J., Christmas, Stephen E., Neoptolemos, John P., and Slavin, John

Subjects
Physiology -- Research, Pancreas -- Secretions, Pancreatitis -- Research, Rats -- Research, Cytokines -- Physiological aspects, Neutrophils -- Physiological aspects, Biological sciences
Abstract

MCP-1 but not CINC synthesis is increased in rat pancreatic acini in response to cerulein hyperstimulation. Am J Physiol Gastrointest Liver Physiol 282: G77-G85, 2002; 10.1152/ ajpgi.00031.2002.--Inflammatory mediators including chemokines play a critical role in acute pancreatitis. The precise nature of early inflammatory signals within the pancreas remains, however, unclear. We examined the ability of isolated pancreatic acini to synthesize CC chemokine monocyte chemotactic protein-1 (MCP-1) and CXC chemokine cytokine-induced neutrophil chemoattractant (CINC) and the response to the secretagogue cerulein at physiological and supraphysiological concentrations. Isolated rat pancreatic acini maintained in short-term ([greater than or equal to] 48 h) primary culture constitutively synthesized MCP-1 and CINC. Cerulein ([10.sup.-7] M; supramaximal dose) increased production of MCP-1 but not CINC. Cerulein-induced increase in MCP-1 synthesis was accompanied by increase in nuclear factor (NF)-[kappa]B activation shown by EMSA. Pretreatment with NF-[kappa]B inhibitors N-acetylcysteine (NAC) and N-tosylphenyalanine chloromethyl ketone (TPCK) blocked cerulein-induced NF-KB activation and abolished cerulein's effect on MCP-1 synthesis. Pretreatment with calcium antagonist BAPTA-AM also blocked cerulein's effect on MCP-1 synthesis. These results indicate that isolated acini synthesize MCP-1 and CINC and support the idea of acinar-derived chemokines as early mediators of inflammatory response in acute pancreatitis. Although cerulein hyperstimulation increased MCP-1 synthesis by a calciumdependent mechanism involving NF-[kappa]B activation, CINC synthesis was not affected. This suggests that regulation of CC and CXC chemokines within acinar cells may be quite different. monocyte chemotactic protein-i; cytokine-induced neutrophil chemoattractant; nuclear factor-[kappa]B.

Published
2002

26. The CXCR6/CXCL16 axis links inflamm-aging to disease severity in COVID-19 patients

Author

Payne, Daniel J., primary, Dalal, Surita, additional, Leach, Richard, additional, Parker, Richard, additional, Griffin, Stephen, additional, McKimmie, Clive S., additional, Cook, Graham P., additional, Richards, Stephen J., additional, Hillmen, Peter, additional, Munir, Talha, additional, Arnold, Louise, additional, Riley, Kathryn, additional, McKinley, Claire, additional, Place, Sandra, additional, Baretto, Richard L., additional, and Newton, Darren J., additional

Published
2021
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31. Normal human enthesis harbours conventional CD4+ and CD8+ T cells with regulatory features and inducible IL-17A and TNF expression

Author

Watad, Abdulla, primary, Rowe, Hannah, additional, Russell, Tobias, additional, Zhou, Qiao, additional, Anderson, Lisa K, additional, Khan, Almas, additional, Dunsmuir, Robert, additional, Loughenbury, Peter, additional, Borse, Vishal, additional, Rao, Abhay, additional, Millner, Peter A, additional, Bragazzi, Nicola Luigi, additional, Amital, Howard, additional, Cuhtbert, Richard, additional, Wittmann, Miriam, additional, Sharif, Kassem, additional, Kenna, Tony, additional, Brown, Matthew A, additional, Newton, Darren, additional, Bridgewood, Charlie, additional, and McGonagle, Dennis G, additional

Published
2020
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32. Patients with paroxysmal nocturnal hemoglobinuria demonstrate a prothrombotic clotting phenotype which is improved by complement inhibition with eculizumab

Author

Macrae, Fraser L., primary, Peacock‐Young, Barnaby, additional, Bowman, Polly, additional, Baker, Stephen R., additional, Quested, Sam, additional, Linton, Emma, additional, Hillmen, Peter, additional, Griffin, Morag, additional, Munir, Talha, additional, Payne, Daniel, additional, McKinley, Claire, additional, Clarke, Deborah, additional, Newton, Darren J, additional, Hill, Anita, additional, and Ariëns, Robert A. S., additional

Published
2020
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33. Presentation clinical, haematological and immunophenotypic features of 1081 patients with GPI‐deficient (paroxysmal nocturnal haemoglobinuria) cells detected by flow cytometry

Author

Richards, Stephen J., primary, Dickinson, Anita J., additional, Cullen, Matthew J., additional, Griffin, Morag, additional, Munir, Tahla, additional, McKinley, Claire, additional, Mitchell, Lindsay D., additional, Newton, Darren J., additional, Arnold, Louise, additional, Hill, Anita, additional, and Hillmen, Peter, additional

Published
2020
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34. Early Emergence of CD19-Negative Human Antibody-Secreting Cells at the Plasmablast to Plasma Cell Transition

Author

Arumugakani, Gururaj, Stephenson, Sophie J., Newton, Darren J., Rawstron, Andy, Emery, Paul, Doody, Gina M., McGonagle, Dennis, and Tooze, Reuben M.

Subjects
Antigens, CD19, Plasma Cells, Humans, Clinical and Human Immunology, Bone Marrow Cells, Cell Differentiation, Antibody-Producing Cells, Flow Cytometry, Lymphocyte Activation, humanities, Cellular Senescence, Immunophenotyping
Abstract

Long-lived human plasma cells (PCs) play central roles in immunity and autoimmunity and are enriched among the subpopulation of CD19neg human PCs. However, whether human CD19neg PCs are necessarily aged cells that have gradually lost CD19 expression is not known. Assessing peripheral blood samples at steady-state and during the acute response to influenza vaccination in healthy donors, we identify the presence of phenotypic CD19neg plasmablasts, the proliferative precursor state to mature PCs, and demonstrate by ELISPOT that these are Ab-secreting cells (ASCs). During the acute response to influenza vaccination, CD19pos, CD19low, and CD19neg ASCs secrete vaccine-specific Abs and show linked IGHV repertoires. To address precursor/product relationships, we use in vitro models that mimic T-dependent and T-independent differentiation, finding that the CD19neg state can be established at the plasmablast to PC transition, that CD19neg PCs increase as a percentage of surviving PCs in vitro, and that CD19neg and CD19pos PCs can be maintained independently. These data provide proof-of-principle for the view that newly generated ASCs can acquire a mature PC phenotype that is accompanied by loss of CD19 expression at an early stage of differentiation and that aging is not an obligate requirement for a CD19neg state to be established.

Published
2017

38. Exploratory Study ofMYD 88L265P, RareNLRP 3Variants, and Clonal Hematopoiesis Prevalence in Patients With Schnitzler Syndrome

Author

Pathak, Shelly, primary, Rowczenio, Dorota M., additional, Owen, Roger G., additional, Doody, Gina M., additional, Newton, Darren J., additional, Taylor, Claire, additional, Taylor, Jan, additional, Cargo, Catherine, additional, Hawkins, Philip N., additional, Krause, Karoline, additional, Lachmann, Helen J., additional, and Savic, Sinisa, additional

Published
2019
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39. Evidence that tissue resident human enthesis γδT-cells can produce IL-17A independently of IL-23R transcript expression

Author

Cuthbert, Richard James, primary, Watad, Abdulla, additional, Fragkakis, Evangelos M, additional, Dunsmuir, Robert, additional, Loughenbury, Peter, additional, Khan, Almas, additional, Millner, Peter A, additional, Davison, Adam, additional, Marzo-Ortega, Helena, additional, Newton, Darren, additional, Bridgewood, Charlie, additional, and McGonagle, Dennis G, additional

Published
2019
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43. Exploratory Study of MYD88 L265P, Rare NLRP3 Variants, and Clonal Hematopoiesis Prevalence in Patients With Schnitzler Syndrome.

Author

Pathak, Shelly, Rowczenio, Dorota M., Owen, Roger G., Doody, Gina M., Newton, Darren J., Taylor, Claire, Taylor, Jan, Cargo, Catherine, Hawkins, Philip N., Krause, Karoline, Lachmann, Helen J., and Savic, Sinisa

Subjects
ALLELES, CARRIER proteins, CHROMOSOMES, GENES, HEALTH facilities, HEMATOPOIESIS, GENETIC mutation, MYELODYSPLASTIC syndromes, POLYMERASE chain reaction, OLIGONUCLEOTIDE arrays, SCHNITZLER syndrome, CRYOPYRIN-associated periodic syndromes
Abstract

Objective: To assess the prevalence of the MYD88 L265P mutation and variants within NLRP3 and evaluate the status of oligoclonal hematopoiesis in 30 patients with Schnitzler syndrome (SchS). Methods: Thirty patients with SchS were recruited from 3 clinical centers. Six patients with known acquired cryopyrin‐associated periodic syndromes (aCAPS) were included as controls. Allele‐specific oligonucleotide–polymerase chain reaction was used for the detection of the MYD88 L265P variant, next‐generation sequencing was applied to analyze NLRP3 and 28 genes associated with myelodysplastic syndrome, and gene scanning was performed for the detection of X chromosome inactivation. Results: Activating NLRP3 mutations were not present in 11 SchS patients who had not been sequenced for this gene previously. The MYD88 L265P variant was present in 9 of 30 SchS patients, and somatic mutations associated with clonal hematopoiesis were identified in 1 of 30 patients with SchS and 1 of 6 patients with aCAPS. Evidence of nonrandom X chromosome inactivation was detected in 1 female patient with SchS and 1 female patient with aCAPS. Conclusion: A shared molecular mechanism accounting for the pathogenesis of inflammation in SchS remains elusive. Clonal hematopoiesis is not associated with other somatic mutations found in individuals with SchS or aCAPS. [ABSTRACT FROM AUTHOR]

Published
2019
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44. Monoclonal B-cell lymphocytosis in a hospital-based UK population and a rural Ugandan population : a cross-sectional study

Author

Rawstron, Andy C., Ssemaganda, Aloysius, de Tute, Ruth, Doughty, Chi, Newton, Darren, Vardi, Anna, Evans, Paul A. S., Stamatopoulos, Kostas, Owen, Roger G., Lightfoot, Tracy, Wakeham, Katie, Karabarinde, Alex, Asiki, Gershim, Newton, Robert, Rawstron, Andy C., Ssemaganda, Aloysius, de Tute, Ruth, Doughty, Chi, Newton, Darren, Vardi, Anna, Evans, Paul A. S., Stamatopoulos, Kostas, Owen, Roger G., Lightfoot, Tracy, Wakeham, Katie, Karabarinde, Alex, Asiki, Gershim, and Newton, Robert

Abstract

Background Reported incidence of B-cell malignancies shows substantial geographical variation, being more common in the Americas and Europe than in Africa. This variation might reflect differences in diagnostic capability, inherited susceptibility, and infectious exposures. Monoclonal B-cell lymphocytosis (MBL) is a precursor lesion that can be screened for in apparently healthy people, allowing comparison of prevalence across different populations independently of health-care provision. We aimed to compare the prevalence and phenotypic characteristics of MBL in age-and-sex-matched populations from rural Uganda and the UK. Methods In this cross-sectional study, we recruited volunteers aged at least 45 years who were seronegative for HIV-1 from the established Ugandan General Population Cohort and obtained their whole-blood samples. We also obtained blood samples from anonymised waste material of age-and-sex-matched individuals (aged >45 years, with a normal blood count and no history of cancer) in the UK. We used flow cytometry to determine the presence of MBL, defined according to standard diagnostic criteria, in the samples and compared differences in the proportion of cases with chronic lymphocytic leukaemia (CLL)-phenotype MBL and CD5-negative MBL, as well as differences in absolute monoclonal B-cell count between the two cohorts. Findings Between Jan 15 and Dec 18, 2012, we obtained samples from 302 Ugandan volunteers and 302 UK individuals who were matched by age and sex to the Ugandan population. Overall MBL prevalence was higher in the Ugandan participants (42 [14%] individuals) than in the UK cohort (25 [8%]; p=0.038). CLL-phenotype MBL was detected in three (1%) Ugandan participants and 21 (7%) UK participants (p=0.00021); all three Ugandan participants had absolute monoclonal B-cell count below one cell per mu L, whereas the 21 UK participants had a median absolute number of circulating neoplastic cells of 4.6 (IQR 2-12) cells per mu L. The prevalence

Published
2017
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46. Highly selective SYK inhibitor, GSK143, abrogates survival signals in chronic lymphocytic leukaemia.

Author

Varghese, Abraham M., Rawstron, Andy, Newton, Darren, Tooze, Reuben M., Munir, Talha, Dickson, Marion, Doody, Gina M., and Hillmen, Peter

Subjects
ANTIGENS, PATHOLOGICAL physiology, B cell receptors, KINASE inhibitors, CHRONIC lymphocytic leukemia, LYMPHOMAS
Abstract

The article focuses on role of antigen stimulation in the pathophysiology of the disease and the development of B cell receptor (BCR) kinase inhibitors as potential therapeutic targets for expansion chronic lymphocytic leukaemia (CLL) research. It mentions aspects of CLL cell survival signalling and to be clinically effective in B-cell non-Hodgkin lymphoma (B-NHL). It also mentions series of diaminopyrimidine carboxamides (DAPC) with SYK inhibitory activity.

Published
2018
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