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1. Evaluation of walking activity and gait to identify physical and mental fatigue in neurodegenerative and immune disorders: preliminary insights from the IDEA-FAST feasibility study

Author

Hinchliffe, Chloe, Rehman, Rana Zia Ur, Pinaud, Clemence, Branco, Diogo, Jackson, Dan, Ahmaniemi, Teemu, Guerreiro, Tiago, Chatterjee, Meenakshi, Manyakov, Nikolay V., Pandis, Ioannis, Davies, Kristen, Macrae, Victoria, Aufenberg, Svenja, Paulides, Emma, Hildesheim, Hanna, Kudelka, Jennifer, Emmert, Kirsten, Van Gassen, Geert, Rochester, Lynn, van der Woude, C. Janneke, Reilmann, Ralf, Maetzler, Walter, Ng, Wan-Fai, and Del Din, Silvia

Published
2024
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3. Genome-wide association study identifies Sjögrens risk loci with functional implications in immune and glandular cells.

Author

Khatri, Bhuwan, Tessneer, Kandice, Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara, Baecklund, Eva, Brun, Johan, Bucher, Sara, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart, Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke, Johnsen, Svein, Jonsson, Malin, Kvarnström, Marika, Kelly, Jennifer, Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna, Taylor, Kimberly, Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel, Grundahl, Kiely, Hefner, Kimberly, Radfar, Lida, Lewis, David, Stone, Donald, Kaufman, C, Brennan, Michael, Guthridge, Joel, James, Judith, Scofield, R, Gaffney, Patrick, Criswell, Lindsey, Jonsson, Roland, Eriksson, Per, Bowman, Simon, Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A, Mariette, Xavier, Alarcon-Riquelme, Marta, Shiboski, Caroline, Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy, Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher

Subjects
Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Sjogrens Syndrome
Abstract

Sjögrens disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögrens cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.

Published
2022

4. Safety and efficacy of subcutaneous iscalimab (CFZ533) in two distinct populations of patients with Sjögren's disease (TWINSS): week 24 results of a randomised, double-blind, placebo-controlled, phase 2b dose-ranging study

Author

Maid, Pablo, Rillo, Oscar, Inderjeeth, Charles, Scheinecker, Clemens, Hermann, Josef, Marcolino, Flora Maria D'Andrea, Dias, Laiza H, Scafuto, Antonio, Bookman, Arthur AM, Fortin, Isabelle, Morin, Frederic, Goio, Elizabeth Jean Moreno, Pezo Ruiz, Ninette, Roman Zamoran, Carlos Patricio, Gonzalez Abarzua, Ivan Antonio, Elgueta, Sergio Fabian, Forero Illera, Elias Gonzalo, Marquez Herndez, Javier Dario, Garcia, Alex Echeverri, Pensec, Valerie Devauchelle, Hachulla, Eric, Mariette, Xavier, Gottenberg, Jacques-Eric, Le Guern, Veronique, Finzel, Stephanie, Schaefer, Valentin, Tony, Hans-Peter, Thomas Schmalzing, Marc, Tausche-Wunderlich, Anne-Kathrin, Tzioufas, Athanasios, Balog, Attila, Rojkovich, Bernadette, Varga, Tunde, Lidar, Merav, Rosner, Itzhak, Levy, Yair, Dagna, Lorenzo, Mosca, Marta, Quartuccio, Luca, Nishiyama, Susumu, Kodera, Masanari, Kaneko, Yuko, Okada, Masato, Ueki, Yukitaka, Hwan Park, Sung, van Daele, Paulus Leon Arthur, Bootsma, Hendrika, Duarte Barcelos, Filipe Alexandre, Crispim Romao, Vasco Madeira, Raimundo Vinagre, Filipe Manuel, Tavaresda Costa, Jose Antonio, Rednic, Simona, Duca, Liliana, Maslyanskiy, Alexey, Yakupova, Svetlana, Bugrova, Olga, Izmozherova, Nadezhda, Zotkin, Evgenyi, Nikolaevna Anoshenkova, Olga, Kvarnstrom, Marika, Tufan, Abdurrahman, Fisher, Benjamin, Yee, Chee Seng, Parker, Benjamin Joseph, Grader Beck, Thomas, Lawrence Ford, Theresa, Papas, Athena, Carsons, Steven, Thiagarajan, Saravanan, Zero, Domenick, McCoy, Sara, Sandorfi, Nora, Fisher, Benjamin A, Grader-Beck, Thomas, Ng, Wan-Fai, van Daele, P L A, Noaiseh, Ghaith, Elgueta, Sergio, McCoy, Sara S, Akpek, Esen, Bookman, Arthur, Sopala, Monika, Montecchi-Palmer, Michela, Luo, Wen-Lin, Scheurer, Cornelia, and Hueber, Wolfgang

Published
2024
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5. Consensus gene modules strategy identifies candidate blood-based biomarkers for primary Sjögren's disease

Author

Boudjeniba, Cheïma, Soret, Perrine, Trutschel, Diana, Hamon, Antoine, Baloche, Valentin, Chassagnol, Bastien, Desvaux, Emiko, Bichat, Antoine, Aussy, Audrey, Moingeon, Philippe, Lefebvre, Céline, Hubert, Sandra, Alarcon-Riquelmé, Marta, Ng, Wan-Fai, Gottenberg, Jacques-Eric, Schwikowski, Benno, Bombardieri, Michele, van Roon, Joel A.G., Mariette, Xavier, Guedj, Mickaël, Birmele, Etienne, Laigle, Laurence, and Becht, Etienne

Published
2024
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6. Towards Automated Fatigue Assessment using Wearable Sensing and Mixed-Effects Models

Author

Bai, Yang, Guan, Yu, Shi, Jian Qing, and Ng, Wan-Fai

Subjects
Computer Science - Human-Computer Interaction
Abstract

Fatigue is a broad, multifactorial concept that includes the subjective perception of reduced physical and mental energy levels. It is also one of the key factors that strongly affect patients' health-related quality of life. To date, most fatigue assessment methods were based on self-reporting, which may suffer from many factors such as recall bias. To address this issue, in this work, we recorded multi-modal physiological data (including ECG, accelerometer, skin temperature and respiratory rate, as well as demographic information such as age, BMI) in free-living environments and developed automated fatigue assessment models. Specifically, we extracted features from each modality and employed the random forest-based mixed-effects models, which can take advantage of the demographic information for improved performance. We conducted experiments on our collected dataset, and very promising preliminary results were achieved. Our results suggested ECG played an important role in the fatigue assessment tasks., Comment: accepted by ISWC 2020

Published
2021
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7. Identification of distinct subgroups of Sjögren's disease by cluster analysis based on clinical and biological manifestations: data from the cross-sectional Paris-Saclay and the prospective ASSESS cohorts

Author

Nguyen, Yann, Nocturne, Gaëtane, Henry, Julien, Ng, Wan-Fai, Belkhir, Rakiba, Desmoulins, Frédéric, Bergé, Elisabeth, Morel, Jacques, Perdriger, Aleth, Dernis, Emmanuelle, Devauchelle-Pensec, Valérie, Sène, Damien, Dieudé, Philippe, Couderc, Marion, Fauchais, Anne-Laure, Larroche, Claire, Vittecoq, Olivier, Salliot, Carine, Hachulla, Eric, Le Guern, Véronique, Gottenberg, Jacques-Eric, Mariette, Xavier, and Seror, Raphaèle

Published
2024
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8. The Sjögren's Working Group: The 2023 OMERACT meeting and provisional domain generation

Author

Gordon, Rachael A., Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A, Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan-Fai, Mendonça, Jose Alexandre, Wallace, Daniel J, Shea, Beverley, Bruyn, George AW, Goodman, Susan M, Fisher, Benjamin A, Baldini, Chiara, Torralba, Karina D, Bootsma, Hendrika, Akpek, Esen K, Karakus, Sezen, Baer, Alan N, Chakravarty, Soumya D, Terslev, Lene, D'Agostino, Maria-Antonietta, Mariette, Xavier, DiRenzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M., Hammitt, Katherine M., Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Luis, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H., Benyoussef, Anas, Masli, Sharmila, Lee, Adrian Y.S., Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, McCoy, Sara S, and Seror, Raphaele

Published
2024
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9. Fatigue Assessment using ECG and Actigraphy Sensors

Author

Bai, Yang, Guan, Yu, and Ng, Wan-Fai

Subjects
Computer Science - Machine Learning, Computer Science - Computer Vision and Pattern Recognition, Statistics - Machine Learning
Abstract

Fatigue is one of the key factors in the loss of work efficiency and health-related quality of life, and most fatigue assessment methods were based on self-reporting, which may suffer from many factors such as recall bias. To address this issue, we developed an automated system using wearable sensing and machine learning techniques for objective fatigue assessment. ECG/Actigraphy data were collected from subjects in free-living environments. Preprocessing and feature engineering methods were applied, before interpretable solution and deep learning solution were introduced. Specifically, for interpretable solution, we proposed a feature selection approach which can select less correlated and high informative features for better understanding system's decision-making process. For deep learning solution, we used state-of-the-art self-attention model, based on which we further proposed a consistency self-attention (CSA) mechanism for fatigue assessment. Extensive experiments were conducted, and very promising results were achieved., Comment: accepted by ISWC 2020

Published
2020
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10. Author Correction: Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author

Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d’Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglænd, Jonsson, Malin V., Kvarnström, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine Brække, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.

Published
2023
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11. The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue in Participants With Primary Sjögren’s Syndrome

Author

Tarn, Jessica, Evans, Evelyn, Traianos, Emmanuella, Collins, Alexis, Stylianou, Mryto, Parikh, Jehill, Bai, Yang, Guan, Yu, Frith, James, Lendrem, Dennis, Macrae, Victoria, McKinnon, Iain, Simon, Bruce S., Blake, Justyna, Baker, Mark R., Taylor, John Paul, Watson, Stuart, Gallagher, Peter, Blamire, Andrew, Newton, Julia, and Ng, Wan-Fai

Published
2023
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12. Building Reality Checks into the Translational Pathway for Diagnostic and Prognostic Models

Author

Lendrem, Dennis W, Lendrem, B Clare, Pratt, Arthur G, Tarn, Jessica R, Skelton, Andrew, James, Kathryn, McMeekin, Peter, Linsley, Matt, Gillespie, Colin, Cordell, Heather, Ng, Wan-Fai, and Isaacs, John D

Subjects
Statistics - Applications
Abstract

There has been a significant increase in the number of diagnostic and prognostic models published in the last decade. Testing such models in an independent, external validation cohort gives some assurance the model will transfer to a naturalistic, healthcare setting. Of 2,147 published models in the PubMed database, we found just 120 included some kind of separate external validation cohort. Of these studies not all were sufficiently well documented to allow a judgement about whether that model was likely to transfer to other centres, with other patients, treated by other clinicians, using data scored or analysed by other laboratories. We offer a solution to better characterizing the validation cohort and identify the key steps on the translational pathway for diagnostic and prognostic models.

Published
2018

13. Between a ROC and a Hard Place: Using prevalence plots to understand the likely real world performance of biomarkers in the clinic

Author

Lendrem, B Clare, Lendrem, Dennis W, Pratt, Arthur G, Naamane, Najib, McMeekin, Peter, Ng, Wan-Fai, Allen, Joy, Power, Michael, and Isaacs, John D

Subjects
Statistics - Applications
Abstract

The Receiver Operating Characteristic (ROC) curve and the Area Under the Curve (AUC) of the ROC curve are widely used to compare the performance of diagnostic and prognostic assays. The ROC curve has the advantage that it is independent of disease prevalence. However, in this note we remind readers that the performance of an assay upon translation to the clinic is critically dependent upon that very same prevalence. Without an understanding of prevalence in the test population, even robust bioassays with excellent ROC characteristics may perform poorly in the clinic. Instead, simple plots of candidate assay performance as a function of prevalence rate give a more realistic understanding of the likely real-world performance and a greater understanding of the likely impact of variation in that prevalence on translational performance in the clinic.

Published
2018

14. Addressing the clinical unmet needs in primary Sjögren’s Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts

Author

Pezoulas, Vasileios C., Goules, Andreas, Kalatzis, Fanis, Chatzis, Luke, Kourou, Konstantina D., Venetsanopoulou, Aliki, Exarchos, Themis P., Gandolfo, Saviana, Votis, Konstantinos, Zampeli, Evi, Burmeister, Jan, May, Thorsten, Marcelino Pérez, Manuel, Lishchuk, Iryna, Chondrogiannis, Thymios, Andronikou, Vassiliki, Varvarigou, Theodora, Filipovic, Nenad, Tsiknakis, Manolis, Baldini, Chiara, Bombardieri, Michele, Bootsma, Hendrika, Bowman, Simon J., Soyfoo, Muhammad Shahnawaz, Parisis, Dorian, Delporte, Christine, Devauchelle-Pensec, Valérie, Pers, Jacques-Olivier, Dörner, Thomas, Bartoloni, Elena, Gerli, Roberto, Giacomelli, Roberto, Jonsson, Roland, Ng, Wan-Fai, Priori, Roberta, Ramos-Casals, Manuel, Sivils, Kathy, Skopouli, Fotini, Torsten, Witte, A. G. van Roon, Joel, Xavier, Mariette, De Vita, Salvatore, Tzioufas, Athanasios G., and Fotiadis, Dimitrios I.

Published
2022
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15. Author Correction: Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author

Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d’Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglænd, Jonsson, Malin V., Kvarnström, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine Brække, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.

Published
2022
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16. Executive summary: British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease

Author

Price, Elizabeth J, primary, Benjamin, Stuart, additional, Bombardieri, Michele, additional, Bowman, Simon, additional, Carty, Sara, additional, Ciurtin, Coziana, additional, Crampton, Bridget, additional, Dawson, Annabel, additional, Fisher, Benjamin A, additional, Giles, Ian, additional, Glennon, Peter, additional, Gupta, Monica, additional, Hackett, Katie L, additional, Larkin, Genevieve, additional, Ng, Wan-Fai, additional, Ramanan, Athimalaipet V, additional, Rassam, Saad, additional, Rauz, Saaeha, additional, Smith, Guy, additional, Sutcliffe, Nurhan, additional, Tappuni, Anwar, additional, and Walsh, Stephen B, additional

Published
2024
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17. British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease

Author

Price, Elizabeth J, primary, Benjamin, Stuart, additional, Bombardieri, Michele, additional, Bowman, Simon, additional, Carty, Sara, additional, Ciurtin, Coziana, additional, Crampton, Bridget, additional, Dawson, Annabel, additional, Fisher, Benjamin A, additional, Giles, Ian, additional, Glennon, Peter, additional, Gupta, Monica, additional, Hackett, Katie L, additional, Larkin, Genevieve, additional, Ng, Wan-Fai, additional, Ramanan, Athimalaipet V, additional, Rassam, Saad, additional, Rauz, Saaeha, additional, Smith, Guy, additional, Sutcliffe, Nurhan, additional, Tappuni, Anwar, additional, and Walsh, Stephen B, additional

Published
2024
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23. Consensus gene modules strategy identifies candidate blood-based biomarkers for primary Sjögren's disease

Author

Lab Reumatologie/Klinische Immunologie, Infection & Immunity, MS Reumatologie/Immunologie/Infectie, Boudjeniba, Cheïma, Soret, Perrine, Trutschel, Diana, Hamon, Antoine, Baloche, Valentin, Chassagnol, Bastien, Desvaux, Emiko, Bichat, Antoine, Aussy, Audrey, Moingeon, Philippe, Lefebvre, Céline, Hubert, Sandra, Alarcon-Riquelmé, Marta, Ng, Wan Fai, Gottenberg, Jacques Eric, Schwikowski, Benno, Bombardieri, Michele, van Roon, Joel A.G., Mariette, Xavier, Guedj, Mickaël, Birmele, Etienne, Laigle, Laurence, Becht, Etienne, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, MS Reumatologie/Immunologie/Infectie, Boudjeniba, Cheïma, Soret, Perrine, Trutschel, Diana, Hamon, Antoine, Baloche, Valentin, Chassagnol, Bastien, Desvaux, Emiko, Bichat, Antoine, Aussy, Audrey, Moingeon, Philippe, Lefebvre, Céline, Hubert, Sandra, Alarcon-Riquelmé, Marta, Ng, Wan Fai, Gottenberg, Jacques Eric, Schwikowski, Benno, Bombardieri, Michele, van Roon, Joel A.G., Mariette, Xavier, Guedj, Mickaël, Birmele, Etienne, Laigle, Laurence, and Becht, Etienne

Published
2024

24. Evaluation of walking activity and gait to identify physical and mental fatigue in neurodegenerative and immune disorders:preliminary insights from the IDEA-FAST feasibility study

Author

Hinchliffe, Chloe, Rehman, Rana Zia Ur, Pinaud, Clemence, Branco, Diogo, Jackson, Dan, Ahmaniemi, Teemu, Guerreiro, Tiago, Chatterjee, Meenakshi, Manyakov, Nikolay V., Pandis, Ioannis, Davies, Kristen, Macrae, Victoria, Aufenberg, Svenja, Paulides, Emma, Hildesheim, Hanna, Kudelka, Jennifer, Emmert, Kirsten, Van Gassen, Geert, Rochester, Lynn, van der Woude, C. Janneke, Reilmann, Ralf, Maetzler, Walter, Ng, Wan Fai, Del Din, Silvia, Hinchliffe, Chloe, Rehman, Rana Zia Ur, Pinaud, Clemence, Branco, Diogo, Jackson, Dan, Ahmaniemi, Teemu, Guerreiro, Tiago, Chatterjee, Meenakshi, Manyakov, Nikolay V., Pandis, Ioannis, Davies, Kristen, Macrae, Victoria, Aufenberg, Svenja, Paulides, Emma, Hildesheim, Hanna, Kudelka, Jennifer, Emmert, Kirsten, Van Gassen, Geert, Rochester, Lynn, van der Woude, C. Janneke, Reilmann, Ralf, Maetzler, Walter, Ng, Wan Fai, and Del Din, Silvia

Abstract

Background: Many individuals with neurodegenerative (NDD) and immune-mediated inflammatory disorders (IMID) experience debilitating fatigue. Currently, assessments of fatigue rely on patient reported outcomes (PROs), which are subjective and prone to recall biases. Wearable devices, however, provide objective and reliable estimates of gait, an essential component of health, and may present objective evidence of fatigue. This study explored the relationships between gait characteristics derived from an inertial measurement unit (IMU) and patient-reported fatigue in the IDEA-FAST feasibility study. Methods: Participants with IMIDs and NDDs (Parkinson's disease (PD), Huntington's disease (HD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren’s syndrome (PSS), and inflammatory bowel disease (IBD)) wore a lower-back IMU continuously for up to 10 days at home. Concurrently, participants completed PROs (physical fatigue (PF) and mental fatigue (MF)) up to four times a day. Macro (volume, variability, pattern, and acceleration vector magnitude) and micro (pace, rhythm, variability, asymmetry, and postural control) gait characteristics were extracted from the accelerometer data. The associations of these measures with the PROs were evaluated using a generalised linear mixed-effects model (GLMM) and binary classification with machine learning. Results: Data were recorded from 72 participants: PD = 13, HD = 9, RA = 12, SLE = 9, PSS = 14, IBD = 15. For the GLMM, the variability of the non-walking bouts length (in seconds) with PF returned the highest conditional R2, 0.165, and with MF the highest marginal R2, 0.0018. For the machine learning classifiers, the highest accuracy of the current analysis was returned by the micro gait characteristics with an intrasubject cross validation method and MF as 56.90% (precision = 43.9%, recall = 51.4%). Overall, the acceleration vector magnitude, bout length variation, postural control, and gait rhythm were

Published
2024

25. Examining the biological pathways underlying clinical heterogeneity in Sjogren's syndrome : proteomic and network analysis

Author

Berry, Joe Scott, Tarn, Jessica, Casement, John, Duret, Pierre-Marie, Scott, Lauren, Wood, Karl, Johnsen, Svein-Joar, Nordmark, Gunnel, Devauchelle-Pensec, Valerie, Seror, Raphaele, Fisher, Benjamin, Barone, Fransesca, Bowman, Simon J., Bombardieri, Michele, Lendrem, Dennis, Felten, Renaud, Gottenberg, Jacques-Eric, Ng, Wan-Fai, Berry, Joe Scott, Tarn, Jessica, Casement, John, Duret, Pierre-Marie, Scott, Lauren, Wood, Karl, Johnsen, Svein-Joar, Nordmark, Gunnel, Devauchelle-Pensec, Valerie, Seror, Raphaele, Fisher, Benjamin, Barone, Fransesca, Bowman, Simon J., Bombardieri, Michele, Lendrem, Dennis, Felten, Renaud, Gottenberg, Jacques-Eric, and Ng, Wan-Fai

Abstract

Objectives: Stratification approaches are vital to address clinical heterogeneity in Sjogren's syndrome (SS). We previously described that the Newcastle Sjogren's Stratification Tool (NSST) identified four distinct clinical subtypes of SS. We performed proteomic and network analysis to analyse the underlying pathobiology and highlight potential therapeutic targets for different SS subtypes. Method: We profiled serum proteins using O-link technology of 180 SS subjects. We used 5 O-link proteomics panels which included a total of 454 unique proteins. Network reconstruction was performed using the ARACNE algorithm, with differential expression estimates overlaid on these networks to reveal the key subnetworks of differential expression. Furthermore, data from a phase III trial of tocilizumab in SS were reanalysed by stratifying patients at baseline using NSST. Results: Our analysis highlights differential expression of chemokines, cytokines and the major autoantigen TRIM21 between the SS subtypes. Furthermore, we observe differential expression of several transcription factors associated with energy metabolism and redox balance namely APE1/Ref-1, FOXO1, TIGAR and BACH1. The differentially expressed proteins were inter-related in our network analysis, supporting the concept that distinct molecular networks underlie the clinical subtypes of SS. Stratification of patients at baseline using NSST revealed improvement of fatigue score only in the subtype expressing the highest levels of serum IL-6. Conclusions: Our data provide clues to the pathways contributing to the glandular and non-glandular manifestations of SS and to potential therapeutic targets for different SS subtypes. In addition, our analysis highlights the need for further exploration of altered metabolism and mitochondrial dysfunction in the context of SS subtypes.

Published
2024
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26. The Sjögren's Working Group:The 2023 OMERACT meeting and provisional domain generation

Author

Gordon, Rachael A., Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A., Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan Fai, Mendonça, Jose Alexandre, Wallace, Daniel J., Shea, Beverley, Bruyn, George AW, Goodman, Susan M., Fisher, Benjamin A., Baldini, Chiara, Torralba, Karina D., Bootsma, Hendrika, Akpek, Esen K., Karakus, Sezen, Baer, Alan N., Chakravarty, Soumya D., Terslev, Lene, D'Agostino, Maria Antonietta, Mariette, Xavier, DiRenzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M., Hammitt, Katherine M., Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Luis, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H., Benyoussef, Anas, Masli, Sharmila, Lee, Adrian Y.S., Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, McCoy, Sara S., Seror, Raphaele, Gordon, Rachael A., Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A., Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan Fai, Mendonça, Jose Alexandre, Wallace, Daniel J., Shea, Beverley, Bruyn, George AW, Goodman, Susan M., Fisher, Benjamin A., Baldini, Chiara, Torralba, Karina D., Bootsma, Hendrika, Akpek, Esen K., Karakus, Sezen, Baer, Alan N., Chakravarty, Soumya D., Terslev, Lene, D'Agostino, Maria Antonietta, Mariette, Xavier, DiRenzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M., Hammitt, Katherine M., Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Luis, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H., Benyoussef, Anas, Masli, Sharmila, Lee, Adrian Y.S., Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, McCoy, Sara S., and Seror, Raphaele

Abstract

Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity, Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.

Published
2024

27. The Sjögren's Working Group: The 2023 OMERACT meeting and provisional domain generation

Author

Gordon, Rachael A, Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A, Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan-Fai, Mendonça, Jose Alexandre, Wallace, Daniel J, Shea, Beverley, Bruyn, George Aw, Goodman, Susan M, Fisher, Benjamin A, Baldini, Chiara, Torralba, Karina D, Bootsma, Hendrika, Akpek, Esen K, Karakus, Sezen, Baer, Alan N, Chakravarty, Soumya D, Terslev, Lene, D'Agostino, Maria Antonietta, Mariette, Xavier, Direnzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M, Hammitt, Katherine M, Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Lui, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H, Benyoussef, Ana, Masli, Sharmila, Lee, Adrian Y S, Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, Mccoy, Sara S, Seror, Raphaele, D'Agostino, Maria-Antonietta (ORCID:0000-0002-5347-0060), Gordon, Rachael A, Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A, Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan-Fai, Mendonça, Jose Alexandre, Wallace, Daniel J, Shea, Beverley, Bruyn, George Aw, Goodman, Susan M, Fisher, Benjamin A, Baldini, Chiara, Torralba, Karina D, Bootsma, Hendrika, Akpek, Esen K, Karakus, Sezen, Baer, Alan N, Chakravarty, Soumya D, Terslev, Lene, D'Agostino, Maria Antonietta, Mariette, Xavier, Direnzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M, Hammitt, Katherine M, Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Lui, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H, Benyoussef, Ana, Masli, Sharmila, Lee, Adrian Y S, Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, Mccoy, Sara S, Seror, Raphaele, and D'Agostino, Maria-Antonietta (ORCID:0000-0002-5347-0060)

Abstract

Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.

Published
2024

28. Therapeutic Recommendations for the Management of Older Adult Patients with Sjögren’s Syndrome

Author

Retamozo, Soledad, Baldini, Chiara, Bootsma, Hendrika, De Vita, Salvatore, Dörner, Thomas, Fisher, Benjamin A., Gottenberg, Jacques-Eric, Hernández-Molina, Gabriela, Kocher, Agnes, Kostov, Belchin, Kruize, Aike A., Mandl, Thomas, Ng, Wan-Fai, Seror, Raphaèle, Shoenfeld, Yehuda, Sisó-Almirall, Antoni, Tzioufas, Athanasios G., Vissink, Arjan, Vitali, Claudio, Bowman, Simon J., Mariette, Xavier, Ramos-Casals, Manuel, and Brito-Zerón, Pilar

Published
2021
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29. Assessment of the anti-CD40 antibody iscalimab in patients with primary Sjögren's syndrome: a multicentre, randomised, double-blind, placebo-controlled, proof-of-concept study

Author

Fisher, Benjamin A, Szanto, Antonia, Ng, Wan-Fai, Bombardieri, Michele, Posch, Maximilian G, Papas, Athena S, Farag, Arwa M, Daikeler, Thomas, Bannert, Bettina, Kyburz, Diego, Kivitz, Alan J, Carsons, Steven E, Isenberg, David A, Barone, Francesca, Bowman, Simon J, Espié, Pascal, Floch, David, Dupuy, Cyrielle, Ren, Xiaohui, Faerber, Petra M, Wright, Andrew M, Hockey, Hans-Ulrich, Rotte, Michael, Milojevic, Julie, Avrameas, Alexandre, Valentin, Marie-Anne, Rush, James S, and Gergely, Peter

Published
2020
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31. The IRF5–TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share

Author

Kottyan, Leah C, Zoller, Erin E, Bene, Jessica, Lu, Xiaoming, Kelly, Jennifer A, Rupert, Andrew M, Lessard, Christopher J, Vaughn, Samuel E, Marion, Miranda, Weirauch, Matthew T, Namjou, Bahram, Adler, Adam, Rasmussen, Astrid, Glenn, Stuart, Montgomery, Courtney G, Hirschfield, Gideon M, Xie, Gang, Coltescu, Catalina, Amos, Chris, Li, He, Ice, John A, Nath, Swapan K, Mariette, Xavier, Bowman, Simon, Rischmueller, Maureen, Lester, Sue, Brun, Johan G, Gøransson, Lasse G, Harboe, Erna, Omdal, Roald, Cunninghame-Graham, Deborah S, Vyse, Tim, Miceli-Richard, Corinne, Brennan, Michael T, Lessard, James A, Wahren-Herlenius, Marie, Kvarnström, Marika, Illei, Gabor G, Witte, Torsten, Jonsson, Roland, Eriksson, Per, Nordmark, Gunnel, Ng, Wan-Fai, Anaya, Juan-Manuel, Rhodus, Nelson L, Segal, Barbara M, Merrill, Joan T, James, Judith A, Guthridge, Joel M, Scofield, R Hal, Alarcon-Riquelme, Marta, Bae, Sang-Cheol, Boackle, Susan A, Criswell, Lindsey A, Gilkeson, Gary, Kamen, Diane L, Jacob, Chaim O, Kimberly, Robert, Brown, Elizabeth, Edberg, Jeffrey, Alarcón, Graciela S, Reveille, John D, Vilá, Luis M, Petri, Michelle, Ramsey-Goldman, Rosalind, Freedman, Barry I, Niewold, Timothy, Stevens, Anne M, Tsao, Betty P, Ying, Jun, Mayes, Maureen D, Gorlova, Olga Y, Wakeland, Ward, Radstake, Timothy, Martin, Ezequiel, Martin, Javier, Siminovitch, Katherine, Sivils, Kathy L Moser, Gaffney, Patrick M, Langefeld, Carl D, Harley, John B, and Kaufman, Kenneth M

Subjects
Biological Sciences, Genetics, Autoimmune Disease, Biotechnology, Lupus, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Autoimmune Diseases, Bayes Theorem, Case-Control Studies, Cohort Studies, DNA-Binding Proteins, Haplotypes, Humans, Interferon Regulatory Factors, Lupus Erythematosus, Systemic, Male, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, beta Karyopherins, UK Primary Sjögren's Syndrome Registry, Medical and Health Sciences, Genetics & Heredity
Abstract

Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.

Published
2015

32. 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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33. Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Author

Devauchelle-Pensec, Valerie, Dieude, Philippe, Dubost, Jean Jacques, Fauchais, Anne-Laure, Goeb, Vincent, Hachulla, Eric, Larroche, Claire, Le Guern, Véronique, Morel, Jacques, Perdriger, Aleth, Puéchal, Xavier, Rist, Stephanie, Sen, Damien, Sibilia, Jean, Vittecoq, Olivier, Benessiano, Joelle, Tubiana, Sarah, Inamo, Karine, Gaete, Stanie, Batouche, Djilali, Molinari, Domitille, Randrianandrasana, Mickael, Pane, Isabelle, Abbe, Adeline, Baron, Gabriel, Ravaud, Philippe, Gottenberg, Jacques-Eric, Saraux, Alain, Devauchelle-Pensec, Valérie, Hayem, Gilles, Hatron, Pierre, Sene, Damien, Zarnitsky, Charles, Furlan, Valérie, Perrodeau, Elodie, Seror, Raphaele, Mariette, Xavier, Brown, S, Navarro, N Coy, Pitzalis, C, Emery, P, Pavitt, S, Gray, J, Hulme, C, Hall, F, Busch, R, Smith, P, Dawson, L, Bombardieri, M, Ng, W-F, Pease, C, Price, E, Sutcliffe, N, Woods, C, Ruddock, S, Everett, C, Reynolds, C, Skinner, E, Poveda-Gallego, A, Rout, J, Macleod, I, Rauz, S, Bowman, S, Ng, Wan-Fai, Bowman, Simon J, Griffiths, Bridget, Hall, Frances, Bacaba, Elalaine C, Frankland, Helen, Moots, Robert, Chadravarty, Kuntal, Lamabadusuriya, Shamin, Bombardieri, Michele, Pitzalis, Constantino, Sutcliffe, Nurhan, Breston, Celia, Gendi, Nagui, Culfear, Karen, Riddell, Claire, Hamburger, John, Richards, Andrea, Rauz, Saaeh, Brailsford, Sue, Dasgin, Joanne, Logan, Joanne, Mulherin, Diarmuid, Andrews, Jacqueline, Emery, Pau, McManus, Alison, Pease, Colin, Pickles, David, Booth, Alison, Regan, Marian, Kin, Jon King, Holt, Amanda, Dimitroulas, Theodoros, Kadiki, Lucy, Kaur, Daljit, Kitas, George, Khan, Abdul, Cosier, Tracey, Panthakalam, Mintrim, Kell, Lloyd, Mark, Moore, Lisa, Gordon, Esther, Lawson, Cathy, Gupta, Monica, Hunter, John, Stirton, Lesley, Ortiz, Gill, Price, Elizabeth, Pelger, Suzannah, Gorman, Claire, Hans, Balinder, Clunie, Gavin, Lane, Suzanne, Rose, Ginny, Cuckow, Sue, Batley, Michael, Einosas, Ruby, Knight, Susan, Symmons, Deborah, Jones, Beverley, Carr, Andrew, Edgar, Suzanne, Figuereido, Francisco, Foggo, Heather, Lendrem, Dennis, Macleod, Iain, Mitchell, Sheryl, Downie, Christine, Tarn, Jessica, Locke, James, Al-Ali, Shereen, Legg, Sarah, Mirza, Kamran, Hargreaves, Ben, Hetherington, Laura, Jones, Adrian, Lanyon, Peter, Muir, Alice, White, Paula, Young-Min, Steven, Pugmire, Susan, Vadivelu, Saravanan, Cooper, Annie, Watkins, Marianne, Field, Anne, Kaye, Stephen, Mewar, Devesh, Medcalf, Patricia, Tomlinson, Pamela, Whiteside, Debbie, McHugh, Neil, Pauling, John, James, Julie, Dowden, Andrea, Akil, Mohammed, McDermott, Jayne, Godia, Olivia, Coady, David, Kidd, Elizabeth, Palmer, Lynne, Li, Charles, Bartrum, Sarah, Mead, De, Dasgupta, Bhaskar, Katsande, Victoria, Long, Pamela, Vermaak, Erin, Turner, Janet, Chandra, Usha, MacKay, Kirsten, Fedele, Stefano, Ferenkeh-Koroma, Ada, Giles, Ian, Isenberg, David, MaConnell, Helena, Ahwiren, Nyarko, Porter, Stephen, Allcoa, Paul, McLaren, John, Tarn, Jessica R, Howard-Tripp, Nadia, Lendrem, Dennis W, Skelton, Andrew J, James, Katherine, McMeekin, Peter, Hackett, Katie L, Lendrem, B Clare, Casement, John, Pease, Colin T, Emery, Paul, Pitzalis, Costantino, Saravanan, Vadivelu, Johnsen, Svein J A, Norheim, Katrine B, Omdal, Roald, Stocken, Deborah, Everett, Colin, Fernandez, Catherine, and Isaacs, John D

Published
2019
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36. Safety and efficacy of subcutaneous iscalimab (CFZ533) in two distinct populations of patients with Sjögren's disease (TWINSS): week 24 results of a randomised, double-blind, placebo-controlled, phase 2b dose-ranging study

Author

Fisher, Benjamin A, Mariette, Xavier, Papas, Athena, Grader-Beck, Thomas, Bootsma, Hendrika, Ng, Wan-Fai, van Daele, P L A, Finzel, Stephanie, Noaiseh, Ghaith, Elgueta, Sergio, Hermann, Josef, McCoy, Sara S, Akpek, Esen, Bookman, Arthur, Sopala, Monika, Montecchi-Palmer, Michela, Luo, Wen-Lin, Scheurer, Cornelia, Hueber, Wolfgang, Maid, Pablo, Rillo, Oscar, Inderjeeth, Charles, Scheinecker, Clemens, Hermann, Josef, Marcolino, Flora Maria D'Andrea, Dias, Laiza H, Scafuto, Antonio, Bookman, Arthur AM, Fortin, Isabelle, Morin, Frederic, Goio, Elizabeth Jean Moreno, Pezo Ruiz, Ninette, Roman Zamoran, Carlos Patricio, Gonzalez Abarzua, Ivan Antonio, Elgueta, Sergio Fabian, Forero Illera, Elias Gonzalo, Marquez Herndez, Javier Dario, Garcia, Alex Echeverri, Pensec, Valerie Devauchelle, Hachulla, Eric, Mariette, Xavier, Gottenberg, Jacques-Eric, Le Guern, Veronique, Finzel, Stephanie, Schaefer, Valentin, Tony, Hans-Peter, Thomas Schmalzing, Marc, Tausche-Wunderlich, Anne-Kathrin, Tzioufas, Athanasios, Balog, Attila, Rojkovich, Bernadette, Varga, Tunde, Lidar, Merav, Rosner, Itzhak, Levy, Yair, Dagna, Lorenzo, Mosca, Marta, Quartuccio, Luca, Nishiyama, Susumu, Kodera, Masanari, Kaneko, Yuko, Okada, Masato, Ueki, Yukitaka, Hwan Park, Sung, van Daele, Paulus Leon Arthur, Bootsma, Hendrika, Duarte Barcelos, Filipe Alexandre, Crispim Romao, Vasco Madeira, Raimundo Vinagre, Filipe Manuel, Tavaresda Costa, Jose Antonio, Rednic, Simona, Duca, Liliana, Maslyanskiy, Alexey, Yakupova, Svetlana, Bugrova, Olga, Izmozherova, Nadezhda, Zotkin, Evgenyi, Nikolaevna Anoshenkova, Olga, Kvarnstrom, Marika, Tufan, Abdurrahman, Fisher, Benjamin, Yee, Chee Seng, Parker, Benjamin Joseph, Grader Beck, Thomas, Lawrence Ford, Theresa, Papas, Athena, Carsons, Steven, Thiagarajan, Saravanan, Zero, Domenick, McCoy, Sara, and Sandorfi, Nora

Abstract

Sjögren's disease is a chronic autoimmune disease with an unmet need for targeted therapies. The aim of the TWINSS study is to evaluate the safety and efficacy of iscalimab, a monoclonal antibody against CD40, in patients with active Sjögren's disease.

Published
2024
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38. Serum and Tissue Biomarkers Associated With Composite of Relevant Endpoints for Sjögren Syndrome (CRESS) and Sjögren Tool for Assessing Response (STAR) to B Cell–Targeted Therapy in the Trial of Anti–B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS)

Author

Pontarini, Elena, Sciacca, Elisabetta, Chowdhury, Farzana, Grigoriadou, Sofia, Rivellese, Felice, Murray‐Brown, William J., Lucchesi, Davide, Fossati‐Jimack, Liliante, Nerviani, Alessandra, Jaworska, Edyta, Ghirardi, Giulia Maria, Giacomassi, Chiara, Emery, Paul, Ng, Wan Fai, Sutcliffe, Nurhan, Everett, Colin, Fernandez, Catherine, Tappuni, Anwar, Seror, Raphael, and Mariette, Xavier

Subjects
SALIVARY gland physiology, PERIPHERAL nervous system, DENTAL resins, BIOPSY, FLOW cytometry, IMMUNOPHENOTYPING, CHEMOKINES, EPITHELIAL cells, TISSUES, PLACEBOS, T-test (Statistics), DATA analysis, EXOCRINE glands, KRUSKAL-Wallis Test, FISHER exact test, CELLULAR therapy, RITUXIMAB, TRANSCRIPTION factors, QUANTITATIVE research, MANN Whitney U Test, CHI-squared test, DESCRIPTIVE statistics, SERUM, LONGITUDINAL method, PRE-tests & post-tests, MESSENGER RNA, GENES, ANTIGENS, EPITHELIUM, STATISTICS, ANALYSIS of variance, SJOGREN'S syndrome, CYTOKINES, INFLAMMATION, LYMPHOID tissue, DATA analysis software, BIOMARKERS, B cells, SEQUENCE analysis, INTERLEUKINS, TUMOR necrosis factors, NONPARAMETRIC statistics
Abstract

Objective: This study aimed to identify peripheral and salivary gland (SG) biomarkers of response/resistance to B cell depletion based on the novel concise Composite of Relevant Endpoints for Sjögren Syndrome (cCRESS) and candidate Sjögren Tool for Assessing Response (STAR) composite endpoints. Methods: Longitudinal analysis of peripheral blood and SG biopsies was performed pre‐ and post‐treatment from the Trial of Anti–B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS) combining flow cytometry immunophenotyping, serum cytokines, and SG bulk RNA sequencing. Results: Rituximab treatment prevented the worsening of SG inflammation observed in the placebo arm, by inhibiting the accumulation of class‐switched memory B cells within the SG. Furthermore, rituximab significantly down‐regulated genes involved in immune‐cell recruitment, lymphoid organization alongside antigen presentation, and T cell co‐stimulatory pathways. In the peripheral compartment, rituximab down‐regulated immunoglobulins and auto‐antibodies together with pro‐inflammatory cytokines and chemokines. Interestingly, patients classified as responders according to STAR displayed significantly higher baseline levels of C‐X‐C motif chemokine ligand‐13 (CXCL13), interleukin (IL)‐22, IL‐17A, IL‐17F, and tumor necrosis factor‐α (TNF‐α), whereas a longitudinal analysis of serum T cell–related cytokines showed a selective reduction in both STAR and cCRESS responder patients. Conversely, cCRESS response was better associated with biomarkers of SG immunopathology, with cCRESS‐responders showing a significant decrease in SG B cell infiltration and reduced expression of transcriptional gene modules related to T cell costimulation, complement activation, and Fcγ‐receptor engagement. Finally, cCRESS and STAR response were associated with a significant improvement in SG exocrine function linked to transcriptional evidence of SG epithelial and metabolic restoration. Conclusion: Rituximab modulates both peripheral and SG inflammation, preventing the deterioration of exocrine function with functional and metabolic restoration of the glandular epithelium. Response assessed by newly developed cCRESS and STAR criteria was associated with differential modulation of peripheral and SG biomarkers, emerging as novel tools for patient stratification. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis

Author

Brito-Zerón, Pilar, primary, Flores-Chávez, Alejandra, additional, Ng, Wan-Fai, additional, Fanny Horváth, Ildiko, additional, Rasmussen, Astrid, additional, Priori, Roberta, additional, Baldini, Chiara, additional, Armagan, Berkan, additional, Özkiziltaş, Burcugül, additional, Praprotnik, Sonja, additional, Suzuki, Yasuori, additional, Quartuccio, Luca, additional, Hernandez-Molina, Gabriela, additional, Abacar, Kerem, additional, Bartoloni, Elena, additional, Rischmueller, Maureen, additional, Reis-de Oliveira, Fabiola, additional, Fernandes Moça Trevisani, Virginia, additional, Jurcut, Ciprian, additional, Fugmann, Cecilia, additional, Carubbi, Francesco, additional, Hofauer, Benedikt, additional, Valim, Valeria, additional, Pasoto, Sandra G., additional, Retamozo, Soledad, additional, Atzeni, Fabiola, additional, Fonseca-Aizpuru, Eva, additional, López-Dupla, Miguel, additional, Giacomelli, Roberto, additional, Nakamura, Hideki, additional, Akasbi, Miriam, additional, Thompson, Kyle, additional, Szántó, Antónia, additional, Farris, A. Darise, additional, Villa, Martina, additional, Bombardieri, Stefano, additional, Kilic, Levent, additional, Tufan, Abdurrahman, additional, Perdan Pirkmajer, Katja, additional, Fujisawa, Yuhei, additional, de Vita, Salvatore, additional, Inanc, Nevsun, additional, and Ramos-Casals, Manuel, additional

Published
2023
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40. Variants in the DDX6-CXCR5 autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland

Author

Wiley, Mandi M, primary, Khatri, Bhuwan, additional, Joachims, Michelle L, additional, Tessneer, Kandice L, additional, Stolarczyk, Anna M, additional, Rasmussen, Astrid, additional, Anaya, Juan-Manuel, additional, Aqrawi, Lara A, additional, Bae, Sang-Cheol, additional, Baecklund, Eva, additional, Bjork, Albin, additional, Brun, Johan G, additional, Bucher, Sara Magnusson, additional, Dand, Nick, additional, Eloranta, Maija-Leena, additional, Engelke, Fiona, additional, Forsblad-d'Elia, Helena, additional, Fugmann, Cecilia, additional, Glenn, Stuart B, additional, Gong, Chen, additional, Gottenberg, Jacques-Eric, additional, Hammenfors, Daniel, additional, Imgenberg-Kreuz, Juliana, additional, Jensen, Janicke Liaaen, additional, Johnsen, Svein Joar Auglaend, additional, Jonsson, Malin V, additional, Kelly, Jennifer A, additional, Khanam, Sharmily, additional, Kim, Kwangwoo, additional, Kvarnstrom, Marika, additional, Mandl, Thomas, additional, Martin, Javier, additional, Morris, David L, additional, Nocturne, Gaetane, additional, Norheim, Katrine Braekke, additional, Olsson, Peter, additional, Palm, Oyvind, additional, Pers, Jacques-Olivier, additional, Rhodus, Nelson L, additional, Sjowall, Christopher, additional, Skarstein, Kathrine, additional, Taylor, Kimberly E, additional, Tombleson, Phil, additional, Thorlacius, Gudny Ella, additional, Venuturupalli, Swamy, additional, Vital, Edward M, additional, Wallace, Daniel J., additional, Grundahl, Kiely M, additional, Radfar, Lida, additional, Brennan, Michael T, additional, James, Judith A, additional, Scofield, R. Hal, additional, Gaffney, Patrick M, additional, Criswell, Lindsey A, additional, Jonsson, Roland, additional, Appel, Silke, additional, Eriksson, Per, additional, Bowman, Simon J, additional, Omdal, Roald, additional, Ronnblom, Lars, additional, Warner, Blake M., additional, Rischmueller, Maureen, additional, Witte, Torsten, additional, Farris, A. Darise, additional, Mariette, Xavier, additional, Shiboski, Caroline H, additional, Wahren-Herlenius, Marie, additional, Alarcon-Riquelme, Marta E, additional, Ng, Wan-Fai, additional, Sivils, Kathy L., additional, Guthridge, Joel M, additional, Adrianto, Indra, additional, Vyse, Timothy J, additional, Tsao, Betty P, additional, Nordmark, Gunnel, additional, and Lessard, Christopher J, additional

Published
2023
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43. Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome

Author

Flores-Chávez, Alejandra, primary, Brito-Zerón, Pilar, additional, Ng, Wan-Fai, additional, Szántó, Antónia, additional, Rasmussen, Astrid, additional, Priori, Roberta, additional, Baldini, Chiara, additional, Armagan, Berkan, additional, Özkiziltaş, Burcugül, additional, Praprotnik, Sonja, additional, Suzuki, Yasunori, additional, Quartuccio, Luca, additional, Hernández-Molina, Gabriela, additional, Inanc, Nevsun, additional, Bartoloni, Elena, additional, Rischmueller, Maureen, additional, Reis-de Oliveira, Fabiola, additional, Fernandes Moça Trevisani, Virginia, additional, Jurcut, Ciprian, additional, Nordmark, Gunnel, additional, Carubbi, Francesco, additional, Hofauer, Benedikt, additional, Valim, Valeria, additional, Pasoto, Sandra G., additional, Retamozo, Soledad, additional, Atzeni, Fabiola, additional, Fonseca-Aizpuru, Eva, additional, López-Dupla, Miguel, additional, Giacomelli, Roberto, additional, Nakamura, Hideki, additional, Akasbi, Miriam, additional, Thompson, Kyle, additional, Fanny Horváth, Ildiko, additional, Farris, A. Darise, additional, Simoncelli, Edoardo, additional, Bombardieri, Stefano, additional, Kilic, Levent, additional, Tufan, Abdurrahman, additional, Perdan Pirkmajer, Katja, additional, Fujisawa, Yuhei, additional, De Vita, Salvatore, additional, Abacar, Kerem, additional, and Ramos-Casals, Manuel, additional

Published
2023
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44. Examining the biological pathways underlying clinical heterogeneity in Sjogren’s syndrome: proteomic and network analysis

Author

Berry, Joe Scott, primary, Tarn, Jessica, additional, Casement, John, additional, Duret, Pierre-Marie, additional, Scott, Lauren, additional, Wood, Karl, additional, Johnsen, Svein-Joar, additional, Nordmark, Gunnel, additional, Devauchelle-Pensec, Valérie, additional, Seror, Raphaele, additional, Fisher, Benjamin, additional, Barone, Fransesca, additional, Bowman, Simon J, additional, Bombardieri, Michele, additional, Lendrem, Dennis, additional, Felten, Renaud, additional, Gottenberg, Jacques-Eric, additional, and Ng, Wan-Fai, additional

Published
2023
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46. Identification of Fatigue and Sleepiness in Immune and Neurodegenerative Disorders from Measures of Real-World Gait Variability

Author

Hinchliffe, Chloe, primary, Rehman, Rana Zia Ur, additional, Branco, Diogo, additional, Jackson, Dan, additional, Ahmaniemi, Teemu, additional, Guerreiro, Tiago, additional, Chatterjee, Meenakshi, additional, Manyakov, Nikolay V., additional, Pandis, Ioannis, additional, Davies, Kristen, additional, Macrae, Victoria, additional, Aufenberg, Svenja, additional, Paulides, Emma, additional, Hildesheim, Hanna, additional, Kudelka, Jennifer, additional, Emmert, Kirsten, additional, Van Gassen, Geert, additional, Rochester, Lynn, additional, van der Woude, C. Janneke, additional, Reilmann, Ralf, additional, Maetzler, Walter, additional, Ng, Wan-Fai, additional, and Din, Silvia Del, additional

Published
2023
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49. Digital endpoints in clinical trials of Alzheimer’s disease and other neurodegenerative diseases: challenges and opportunities

Author

Brem, Anna-Katharine, primary, Kuruppu, Sajini, additional, de Boer, Casper, additional, Muurling, Marijn, additional, Diaz-Ponce, Ana, additional, Gove, Dianne, additional, Curcic, Jelena, additional, Pilotto, Andrea, additional, Ng, Wan-Fai, additional, Cummins, Nicholas, additional, Malzbender, Kristina, additional, Nies, Vera J. M., additional, Erdemli, Gul, additional, Graeber, Johanna, additional, Narayan, Vaibhav A., additional, Rochester, Lynn, additional, Maetzler, Walter, additional, and Aarsland, Dag, additional

Published
2023
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50. Reverse Engineering of Digital Measures: Inviting Patients to the Conversation

Author

Clay, Ieuan, primary, Peerenboom, Nele, additional, Connors, Dana E, additional, Bourke, Steven, additional, Keogh, Alison, additional, Wac, Katarzyna, additional, Gur-Arie, Tova, additional, Baker, Justin, additional, Bull, Christopher, additional, Cereatti, Andrea, additional, Cormack, Francesca, additional, Eggenspieler, Damien, additional, Foschini, Luca, additional, Ganea, Raluca, additional, Groenen, Peter MA, additional, Gusset, Nicole, additional, Izmailova, Elena, additional, Kanzler, Christoph M, additional, Leyens, Lada, additional, Lyden, Kate, additional, Mueller, Arne, additional, Nam, Julian, additional, Ng, Wan-Fai, additional, Nobbs, David, additional, Orfaniotou, Foteini, additional, Perumal, Thanneer Malai, additional, Piwko, Wojciech, additional, Ries, Anja, additional, Scotland, Alf, additional, Taptiklis, Nick, additional, Torous, John, additional, Vereijken, Beatrix, additional, Xu, Shuai, additional, Baltzer, Laurenz, additional, Vetter, Thorsten, additional, Goldhahn, Jörg, additional, and Hoffmann, Steven C, additional

Published
2023
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