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Towards clinical significance of the MUC5B promoter variant and risk of rheumatoid arthritis-associated interstitial lung disease
Jeffrey A Sparks
doi : 10.1136/annrheumdis-2021-220856
Annals of the Rheumatic Diseases 2021;80:1503-1504
Nothing about us without us: involving patient collaborators for machine learning applications in rheumatology
Stephanie J W Shoop-Worrall, Katherine Cresswell, Imogen Bolger, Beth Dillon, Kimme L Hyrich, Nophar Geifman
doi : 10.1136/annrheumdis-2021-220454
Annals of the Rheumatic Diseases 2021;80:1505-1510
Novel machine learning methods open the door to advances in rheumatology through application to complex, high-dimensional data, otherwise difficult to analyse. Results from such efforts could provide better classification of disease, decision support for therapy selection, and automated interpretation of clinical images. Nevertheless, such data-driven approaches could potentially model noise, or miss true clinical phenomena. One proposed solution to ensure clinically meaningful machine learning models is to involve primary stakeholders in their development and interpretation. Including patient and health care professionals’ input and priorities, in combination with statistical fit measures, allows for any resulting models to be well fit, meaningful, and fit for practice in the wider rheumatological community. Here we describe outputs from workshops that involved healthcare professionals, and young people from the Your Rheum Young Person’s Advisory Group, in the development of complex machine learning models. These were developed to better describe trajectory of early juvenile idiopathic arthritis disease, as part of the CLUSTER consortium. We further provide key instructions for reproducibility of this process.Involving people living with, and managing, a disease investigated using machine learning techniques, is feasible, impactful and empowering for all those involved.
Axial spondyloarthritis
Victoria Navarro-Compán, Alexandre Sepriano, Bassel El-Zorkany, Désirée van der Heijde
doi : 10.1136/annrheumdis-2021-221035
Annals of the Rheumatic Diseases 2021;80:1511-1521
Axial spondyloarthritis (axSpA) encompasses both radiographic and non-radiographic axSpA. It is a chronic inflammatory disease with a predilection for involving the axial skeleton. The most common presenting symptoms are chronic back pain and spinal stiffness but peripheral and extra-musculoskeletal manifestations occur also frequently. The diagnosis of axSpA relies on the recognition of a clinical pattern of the disease, based on clinical, laboratory and imaging features. The Assessment in SpondyloArthritis international Society classification criteria for axSpA are valid and well implemented for research purposes. Sustained disease activity, measured by validated tools such as the Ankylosing Spondylitis Disease Activity Score, leads to irreversible structural damage and poor functioning and therefore should be abrogated. As part of the management algorithm, non-steroidal anti-inflammatory drugs remain as the first line of pharmacological treatment besides physiotherapy. As a second line, tumour necrosis factor inhibitor and interleukin-17 inhibitor are available but recently Janus kinase inhibitors have also shown efficacy in improving symptoms of the disease.
Short-term dose and duration-dependent glucocorticoid risk for cardiovascular events in glucocorticoid-naive patients with rheumatoid arthritis
Anthony James Ocon, George Reed, Dimitrios A Pappas, Jeffrey R Curtis, Joel M Kremer
doi : 10.1136/annrheumdis-2021-220577
Annals of the Rheumatic Diseases 2021;80:1522-1529
Rheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiovascular disease. Cardiovascular safety of glucocorticoids in RA is controversial and may be related to dose and duration of use. We determined if initiating glucocorticoids in steroid-naive RA patients would increase cardiovascular event (CVE) risk in a dose and duration-dependent manner over short-term intervals.
Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers
Antti Palomäki, FinnGen Rheumatology Clinical Expert Group, Aarno Palotie, Jukka Koskela, Kari K Eklund, Matti Pirinen, FinnGen, Samuli Ripatti, Tarja Laitinen, Nina Mars
doi : 10.1136/annrheumdis-2021-220698
Annals of the Rheumatic Diseases 2021;80:1530-1536
To estimate lifetime risk of developing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) with respect to the strongest known risk factor for pulmonary fibrosis, a MUC5B promoter variant.
B cell depletion impairs vaccination-induced CD8+ T cell responses in a type I interferon-dependent manner
Theresa Graalmann, Katharina Borst, Himanshu Manchanda, Lea Vaas, Matthias Bruhn, Lukas Graalmann, Mario Koster, Murielle Verboom, Michael Hallensleben, Carlos Alberto Guzmán, Gerd Sutter, Reinhold E Schmidt, Torsten Witte, Ulrich Kalinke
doi : 10.1136/annrheumdis-2021-220435
Annals of the Rheumatic Diseases 2021;80:1537-1544
The monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses.
Impaired fertility in men diagnosed with inflammatory arthritis: results of a large multicentre study (iFAME-Fertility)
Luis Fernando Perez-Garcia, Esther Röder, Robbert J Goekoop, Johanna M W Hazes, Marc R Kok, Hieronymus T W Smeele, Ilja Tchetverikov, Annette H M van der Helm-van Mil, Jos H van der Kaap, Petra Kok, Bouwe P Krijthe, Radboud J E M Dolhain
doi : 10.1136/annrheumdis-2021-220709
Annals of the Rheumatic Diseases 2021;80:1545-1552
The impact of inflammatory arthritis (IA) on male fertility remains unexplored. Our objective was to evaluate the impact of IA on several male fertility outcomes; fertility rate (number of biological children per man), family planning, childlessness and fertility problems.
Role of ultrasound for assessment of psoriatic arthritis patients with fibromyalgia
Ari Polachek, Victoria Furer, Mirna Zureik, Sharon Nevo, Liran Mendel, David Levartovsky, Jonathan Wollman, Valerie Aloush, Reut Tzemach, Ofir Elalouf, Marina Anouk, Mark Berman, Ilana Kaufman, Or Carmi, Yael Lahat, Tali Eviatar, Hagit Padova, Hagit Sarbagil-Maman, Sara Borok, Adi Broyde, Lihi Eder, Daphna Paran, Ori Elkayam
doi : 10.1136/annrheumdis-2021-220562
Annals of the Rheumatic Diseases 2021;80:1553-1558
To investigate whether ultrasonography (US), as an objective imaging modality, can optimise the evaluation of disease activity in psoriatic arthritis (PsA) patients with concomitant fibromyalgia syndrome (FMS).
Ex vivo mass cytometry analysis reveals a profound myeloid proinflammatory signature in psoriatic arthritis synovial fluid
Nicole Yager, Suzanne Cole, Alicia Lledo Lara, Ash Maroof, Frank Penkava, Julian C Knight, Paul Bowness, Hussein Al-Mossawi
doi : 10.1136/annrheumdis-2021-220280
Annals of the Rheumatic Diseases 2021;80:1559-1567
A number of immune populations have been implicated in psoriatic arthritis (PsA) pathogenesis. This study used mass cytometry (CyTOF) combined with transcriptomic analysis to generate a high-dimensional dataset of matched PsA synovial fluid (SF) and blood leucocytes, with the aim of identifying cytokine production ex vivo in unstimulated lymphoid and myeloid cells.
Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) enables accurate and user-friendly definitions of clinical remission and categories of disease activity
Diogo Jesus, Maddalena Larosa, Carla Henriques, Ana Matos, Margherita Zen, Paulo Tomé, Valter Alves, Nuno Costa, Véronique Le Guern, Luca Iaccarino, Nathalie Costedoat-Chalumeau, Andrea Doria, Luís Sousa Inês
doi : 10.1136/annrheumdis-2021-220363
Annals of the Rheumatic Diseases 2021;80:1568-1574
There is an unmet need for accurate and user-friendly definitions of systemic lupus erythematosus (SLE) disease activity and remission. We aimed to derive and validate the SLE Disease Activity Score (SLE-DAS) definitions for disease activity categories and clinical remission state.
Metagenome-wide association study revealed disease-specific landscape of the gut microbiome of systemic lupus erythematosus in Japanese
Yoshihiko Tomofuji, Yuichi Maeda, Eri Oguro-Igashira, Toshihiro Kishikawa, Kenichi Yamamoto, Kyuto Sonehara, Daisuke Motooka, Yuki Matsumoto, Hidetoshi Matsuoka, Maiko Yoshimura, Mayu Yagita, Takuro Nii, Shiro Ohshima, Shota Nakamura, Hidenori Inohara, Kiyoshi Takeda, Atsushi Kumanogoh, Yukinori Okada
doi : 10.1136/annrheumdis-2021-220687
Annals of the Rheumatic Diseases 2021;80:1575-1583
Alteration of the gut microbiome has been linked to the pathogenesis of systemic lupus erythematosus (SLE). However, a comprehensive view of the gut microbiome in SLE and its interaction with the host remains to be revealed. This study aimed to reveal SLE-associated changes in the gut microbiome and its interaction with the host by a comprehensive metagenome-wide association study (MWAS) followed by integrative analysis.
Molecular basis for clinical diversity between autoantibody subsets in diffuse cutaneous systemic sclerosis
Kristina Elizabeth Neergaard Clark, Corrado Campochiaro, Eszter Csomor, Adam Taylor, Katherine Nevin, Nicholas Galwey, Mary A Morse, Jennifer Singh, Yee Voan Teo, Voon H Ong, Emma Derrett-Smith, Nicolas Wisniacki, Shaun M Flint, Christopher P Denton
doi : 10.1136/annrheumdis-2021-220402
Annals of the Rheumatic Diseases 2021;80:1584-1593
Clinical heterogeneity is a cardinal feature of systemic sclerosis (SSc). Hallmark SSc autoantibodies are central to diagnosis and associate with distinct patterns of skin-based and organ-based complications. Understanding molecular differences between patients will benefit clinical practice and research and give insight into pathogenesis of the disease. We aimed to improve understanding of the molecular differences between key diffuse cutaneous SSc subgroups as defined by their SSc-specific autoantibodies
TGF? promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis
Paôline Laurent, Benoit Allard, Pauline Manicki, Valérie Jolivel, Emeline Levionnois, Mohamed Jeljeli, Pauline Henrot, Julien Izotte, Damien Leleu, Alexis Groppi, Julien Seneschal, Joel Constans, Carlo Chizzolini, Christophe Richez, Pierre Duffau, Estibaliz Lazaro, Edouard Forcade, Thierry Schaeverbeke, Thomas Pradeu, Frédéric Batteux, Patrick Blanco, Cécile Contin-Bordes, Marie-Elise Truchetet
doi : 10.1136/annrheumdis-2020-219748
Annals of the Rheumatic Diseases 2021;80:1594-1603
Innate lymphoid cells-2 (ILC2) were shown to be involved in the development of lung or hepatic fibrosis. We sought to explore the functional and phenotypic heterogeneity of ILC2 in skin fibrosis within systemic sclerosis (SSc).
Mechanosensitive TRPV4 is required for crystal-induced inflammation
Zhou Lan, Lvyi Chen, Jing Feng, Zili Xie, Zhiyong Liu, Fang Wang, Peng Liu, Xueping Yue, Lixia Du, Yonghui Zhao, Pu Yang, Jialie Luo, Zhe Zhu, Xueming Hu, Liang Cao, Ping Lu, Rajan Sah, Kory Lavine, Brian Kim, Hongzhen Hu
doi : 10.1136/annrheumdis-2021-220295
Annals of the Rheumatic Diseases 2021;80:1604-1614
Crystal structures activate innate immune cells, especially macrophages and initiate inflammatory responses. We aimed to understand the role of the mechanosensitive TRPV4 channel in crystal-induced inflammation. Real-time RT-PCR, RNAscope in situ hybridisation, and Trpv4eGFP mice were used to examine TRPV4 expression and whole-cell patch-clamp recording and live-cell Ca2+ imaging were used to study TRPV4 function in mouse synovial macrophages and human peripheral blood mononuclear cells (PBMCs). Both genetic deletion and pharmacological inhibition approaches were used to investigate the role of TRPV4 in NLRP3 inflammasome activation induced by diverse crystals in vitro and in mouse models of crystal-induced pain and inflammation in vivo. TRPV4 was functionally expressed by synovial macrophages and human PBMCs and TRPV4 expression was upregulated by stimulation with monosodium urate (MSU) crystals and in human PBMCs from patients with acute gout flares. MSU crystal-induced gouty arthritis were significantly reduced by either genetic ablation or pharmacological inhibition of TRPV4 function. Mechanistically, TRPV4 mediated the activation of NLRP3 inflammasome by diverse crystalline materials but not non-crystalline NLRP3 inflammasome activators, driving the production of inflammatory cytokine interleukin-1? which elicited TRPV4-dependent inflammatory responses in vivo. Moreover, chemical ablation of the TRPV1-expressing nociceptors significantly attenuated the MSU crystal-induced gouty arthritis. In conclusion, TRPV4 is a common mediator of inflammatory responses induced by diverse crystals through NLRP3 inflammasome activation in macrophages. TRPV4-expressing resident macrophages are critically involved in MSU crystal-induced gouty arthritis. A neuroimmune interaction between the TRPV1-expressing nociceptors and the TRPV4-expressing synovial macrophages contributes to the generation of acute gout flares.
14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis
Wenyu Fu, Aubryanna Hettinghouse, Yujianan Chen, Wenhuo Hu, Xiang Ding, Meng Chen, Yuanjing Ding, Jyoti Mundra, Wenhao Song, Ronghan Liu, Young-Su Yi, Mukundan Attur, Jonathan Samuels, Eric Strauss, Philipp Leucht, Ran Schwarzkopf, Chuan-ju Liu
doi : 10.1136/annrheumdis-2021-220000
Annals of the Rheumatic Diseases 2021;80:1615-1627
Osteoarthritis (OA) is the most common joint disease; however, the indeterminate nature of mechanisms by which OA develops has restrained advancement of therapeutic targets. TNF signalling has been implicated in the pathogenesis of OA. TNFR1 primarily mediates inflammation, whereas emerging evidences demonstrate that TNFR2 plays an anti-inflammatory and protective role in several diseases and conditions. This study aims to decipher TNFR2 signalling in chondrocytes and OA.
Early reduction in circulating monocyte count predicts maintenance of remission in patients with rheumatoid arthritis treated with anti-TNF therapy
Muhammad Ruhul Amin Shipa, Raj Amarnani, Su-Ann Yeoh, M D Mainuddin, Michael R Ehrenstein
doi : 10.1136/annrheumdis-2021-220642
Annals of the Rheumatic Diseases 2021;80:1628-1629
Nail involvement in psoriatic arthritis patients is an independent risk factor for carotid plaque
Iris Jazmin Colunga-Pedraza, Dionicio Angel Galarza-Delgado, Jose Ramon Azpiri-Lopez, Alejandra Berenice Rodriguez-Romero, Natalia Guajardo-Jauregui, Jesus Alberto Cardenas-de la Garza, Salvador Lugo-Perez, Alejandro Meza-Garza, Julieta Loya-Acosta, Andrea Cecilia Garza-Acosta
doi : 10.1136/annrheumdis-2021-220782
Annals of the Rheumatic Diseases 2021;80:1629-1631
Tofacitinib for the treatment of antineutrophil cytoplasm antibody-associated vasculitis: a pilot study
Yun Liu, Zongfei Ji, Wensu Yu, Sifan Wu, Huiyong Chen, Lili Ma, Zhenqi Ding, Lindi Jiang
doi : 10.1136/annrheumdis-2021-220484
Annals of the Rheumatic Diseases 2021;80:1631-1633
Immunotherapies and COVID-19 mortality: a multidisciplinary open data analysis based on FDA’s Adverse Event Reporting System
Maximilian Pistor, Andreas G F Hoepner, Yanan Lin, Simon Jung, Claudio L Bassetti, Andrew Chan, Anke Salmen, Robert Hoepner
doi : 10.1136/annrheumdis-2021-220679
Annals of the Rheumatic Diseases 2021;80:1633-1635
Methotrexate and glucocorticoids, but not anticytokine therapy, impair the immunogenicity of a single dose of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic inflammatory arthritis
Serena Bugatti, Ludovico De Stefano, Silvia Balduzzi, Maria Immacolata Greco, Terenzj Luvaro, Irene Cassaniti, Laura Bogliolo, Iolanda Mazzucchelli, Bernardo D’Onofrio, Michele di Lernia, Eleonora Mauric, Daniele Lilleri, Fausto Baldanti, Antonio Manzo, Carlomaurizio Montecucco
doi : 10.1136/annrheumdis-2021-220862
Annals of the Rheumatic Diseases 2021;80:1635-1638
Unexpected impact of COVID-19 lockdown on spinal mobility and health perception in spondyloarthritis
Sophie De Mits, Ann-Sophie De Craemer, Liselotte Deroo, Thomas Renson, Filip E Van den Bosch, Philippe Carron, Dirk Elewaut
doi : 10.1136/annrheumdis-2021-220584
Annals of the Rheumatic Diseases 2021;80:1638-1640
European League against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus: the laboratory immunologist’s point of view
Maria Infantino, Mariangela Manfredi, Nicola Bizzaro
doi : 10.1136/annrheumdis-2019-216591
Annals of the Rheumatic Diseases 2021;80:e188
Response to: ‘European League against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus: the laboratory immunologist's point of view’ by Infantino et al
Martin Aringer, Karen H Costenbader, Thomas Dörner, Sindhu R Johnson
doi : 10.1136/annrheumdis-2019-216700
Annals of the Rheumatic Diseases 2021;80:e189
New 2019 SLE EULAR/ACR classification criteria are valid for identifying patients with SLE among patients admitted for pericardial effusion
Karim Sacre, Laure Delaval, Antoine Dossier, Jean-Francois Alexandra, Marie Berleur, Marie-Paule Chauveheid, Gregory Ducrocq, Tiphaine Goulenok, Damien van Gysel, Diane Rouzaud, Thomas Papo
doi : 10.1136/annrheumdis-2019-216712
Annals of the Rheumatic Diseases 2021;80:e190
Response to: ‘New 2019 SLE EULAR/ACR classification criteria are valid for identifying patients with SLE among patients admitted for pericardial effusion’ by Sacre et al
Martin Aringer, Karen Costenbader, Thomas Dörner, Sindhu R Johnson
doi : 10.1136/annrheumdis-2019-216803
Annals of the Rheumatic Diseases 2021;80:e191
Development and initial validation of diagnostic gene signatures for systemic lupus erythematosus
Bin Wang, Shiju Chen, Qing Zheng, Zhenyu Gao, Rongjuan Chen, Jingxiu Xuan, Yuan Liu, Guixiu Shi
doi : 10.1136/annrheumdis-2019-216695
Annals of the Rheumatic Diseases 2021;80:e192
Response to: ‘Development and initial validation of diagnostic gene signatures for systemic lupus erythematosus’ by Wang et al
Martin Aringer, Karen Costenbader, Thomas Dörner, Sindhu R Johnson
doi : 10.1136/annrheumdis-2019-216807
Annals of the Rheumatic Diseases 2021;80:e193
NCF1-339 polymorphism and systemic lupus erythematosus
Beuy Joob, Viroj Wiwanitkit
doi : 10.1136/annrheumdis-2019-216629
Annals of the Rheumatic Diseases 2021;80:e194
Response to: ‘NCF1-339 polymorphism and systemic lupus erythematosus’ by Joob and Wiwanitkit
Carl Petrus Linge, Anders Bengtsson
doi : 10.1136/annrheumdis-2019-216669
Annals of the Rheumatic Diseases 2021;80:e195
Regulatory T cell frequencies in patients with rheumatoid arthritis are increased by conventional and biological DMARDs but not by JAK inhibitors
Anja Meyer, Paula S Wittekind, Konstantin Kotschenreuther, Joanna Schiller, Julia von Tresckow, Thomas H Haak, David M Kofler
doi : 10.1136/annrheumdis-2019-216576
Annals of the Rheumatic Diseases 2021;80:e196
Response to: ‘Regulatory T cell frequencies in patients with rheumatoid arthritis are increased by conventional and biological DMARDs but not by JAK inhibitors’ by Meyer et al
Michelle Rosenzwajg, Roberta Lorenzon, David Klatzmann
doi : 10.1136/annrheumdis-2019-216598
Annals of the Rheumatic Diseases 2021;80:e197
Correspondence to ‘Slope sign’: a feature of large vessel vasculitis?
Marcin Milchert, Marek Brzosko, Anne Bull Haaversen, Andreas P Diamantopoulos
doi : 10.1136/annrheumdis-2019-216601
Annals of the Rheumatic Diseases 2021;80:e198
Response to: ‘Correspondence to ‘Slope sign’: a feature of large vessel vasculitis?’ by Milchert et al
Alwin Sebastian, Abdul Kayani, Bhaskar Dasgupta
doi : 10.1136/annrheumdis-2019-216690
Annals of the Rheumatic Diseases 2021;80:e199
Clarification regarding the statement of the association between the recombinant zoster vaccine (RZV) and gout flares
Arnaud M Didierlaurent, Christophe Desssart, Anthony L Cunningham
doi : 10.1136/annrheumdis-2019-216639
Annals of the Rheumatic Diseases 2021;80:e200
Response to: ‘Clarification regarding the statement of the association between the recombinant zoster vaccine (RZV) and gout flares’ by Didierlaurent et al
Chio Yokose, Hyon Choi
doi : 10.1136/annrheumdis-2019-216670
Annals of the Rheumatic Diseases 2021;80:e201
Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care
Konstantinos Parperis
doi : 10.1136/annrheumdis-2019-216643
Annals of the Rheumatic Diseases 2021;80:e202
Response to: ‘Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care’ by Parperis et al
Edward Roddy, Christian D Mallen
doi : 10.1136/annrheumdis-2019-216671
Annals of the Rheumatic Diseases 2021;80:e203
Association between osteoporosis and statins therapy: the story continues
Andrea Michelle Burden, Stefan Weiler
doi : 10.1136/annrheumdis-2019-216574
Annals of the Rheumatic Diseases 2021;80:e204
Response to: ‘Association between osteoporosis and statin therapy: the story continues’ by Burden and Weiler
Michael Leutner, Caspar Matzhold, Luise Bellach, Carola Deischinger, Jürgen Harreiter, Stefan Thurner, Peter Klimek, Alexandra Kautzky-Willer
doi : 10.1136/annrheumdis-2019-216627
Annals of the Rheumatic Diseases 2021;80:e205
