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CD1c Dendritic Cells are depleted and accompanied by new HLA-DRhi Phenotypes in Rheumatoid Arthritis Blood medRxiv. Rheumatol. Pub Date : 2024-03-15 Christian Geier, Haani Qudsi, Jihad Ben Gabr, Robert J Winchester, Andras Perl
Rheumatoid arthritis (RA) in an autoimmune disease that leads to inflammation of synovial joints and other organs. Many RA patients "share" a common peptide sequence within the HLA-DR (DR) molecule expressed on antigen-presenting cells (APC), suggesting that DRhi cells are important in RA. Here, we use DRhi to broadly define and immunophenotype RA APC, including potential APC not meeting standard definitions
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Circulating microvesicles as novel biomarkers for pulmonary arterial hypertension in patients with systemic lupus erythematosus medRxiv. Rheumatol. Pub Date : 2024-03-15 Zhe Ding, Fumin Qi, Li Liu, Zhouming Wang, Na Zhang, Xing Lyu, Wenwen Sun, Jun Du, Haoming Haoming, Hou Hou, Ying Guo, Xiaomei Wang, Ming-Lin Liu, Wei Wei
Pulmonary arterial hypertension (PAH) is a serious complication of systemic lupus erythematosus (SLE) with increased mortality. A prothrombotic state may contribute to pathogenesis of SLE-PAH. Microvesicles (MVs) are known to be associated with thrombosis. Here, we investigated circulating MVs and their associations with SLE-PAH. Eighteen SLE-PAH patients, 36 SLE-non-PAH patients, and 36 healthy controls
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Enrichment of Rare Variants of Hemophagocytic Lymphohistiocytosis Genes in Systemic Juvenile Idiopathic Arthritis medRxiv. Rheumatol. Pub Date : 2024-03-15 Mariana Correia Marques, Danielle Rubin, Emily Shuldiner, Mallika Datta, Elizabeth Schmitz, Gustavo Gutierrez Cruz, Andrew Patt, Elizabeth Bennett, Alexei Grom, Dirk Foell, Marco Gattorno, John Bohnsack, Rae S. M. Yeung, Sampath Prahalad, Elizabeth Mellins, Jordi Anton, Claudio Arnaldo Len, Sheila Oliveira, Patricia Woo, Seza Ozen, INCHARGE Consortium, Zuoming Deng, Michael J. Ombrello
Objective: To evaluate whether there is an enrichment of rare variants in familial hemophagocytic lymphohistiocytosis (HLH) genes and systemic juvenile idiopathic arthritis (sJIA) with or without macrophage activation syndrome (MAS). Methods: Targeted sequencing of HLH genes (LYST, PRF1, RAB27A, STX11, STXBP2, UNC13D) was performed in sJIA subjects from an established cohort. Sequence data from control
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Hyperinsulinemia counteracts inflammation by suppressing IFNg and inducing senescence in CD4+ T cells of patients with rheumatoid arthritis medRxiv. Rheumatol. Pub Date : 2024-03-10 Malin C Erlandsson, Lauri Weman, Eric Malmhall-Bah, Venkataragavan Chandrasekaran, Mahomud Tuameh, Karin ME Andersson, Sofia T Silfversward, Lisa Nilsson, Tatiana Zverkova Sandstrom, Rille Pullerits, Mats Dehlin, Tuulikki Sokka-Isler, Maria I Bokarewa
Background. Clinical evidence connects hyperinsulinemia with obesity, and development of type 2 diabetes (T2D). However, its role in autoimmune conditions was questioned. We investigated consequences of hyperinsulinemia for development of T2D and CD4+T cell function in rheumatoid arthritis (RA). Methods. Incident T2D was prospectively studied in two independent RA cohorts and in gout patients matched
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Enhancing gout management by creating a register using automated queries in electronic health records medRxiv. Rheumatol. Pub Date : 2024-03-09 Nils Burgisser, Denis Mongin, Samia Mehouachi, Clement P Buclin, Romain Guemara, Pauline Darbellay Farhoumand, Olivia Braillard, Kim Lauper, Delphine Sophie Courvoisier
Objective: To develop an automatic gout register to improve gout management. Methods: We analysed the electronic health records (EHR) of all patients >18 years old from a tertiary academic hospital (2013-2022) based on six criteria: International Classification of Diseases 10 (ICD-10) gout diagnosis, urate-lowering therapy (ULT) prescription, uric acid crystal in joint aspiration and gout-related terms
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The aconitate decarboxylase 1/itaconate pathway modulates immune dysregulation and associates with cardiovascular disease markers in SLE. medRxiv. Rheumatol. Pub Date : 2024-02-22 Eduardo Patino Martinez, Shuichiro Nakabo, Kan Jiang, Carmelo Carmona- Rivera, Wanxia Li Tsai, Dillon Claybaugh, Zu-Xi Yu, Aracely Romero, Eric Bohrnsen, Benjamin Schwarz, Miguel A. Solis Barbosa, Luz P. Blanco, Mohammad Naqi, Yenealem Temesgen-Oyelakim, Michael Davis, Nehal Mehta, Faiza Naz, Stephen Brooks, Stefania dell Orso, Sarfaraz Hasni, Mariana J. Kaplan
Abstract Objective The Krebs cycle enzyme Aconitate Decarboxylase 1 (ACOD1) mediates itaconate synthesis in myeloid cells.. Previously, we reported that administration of 4-octyl itaconate abrogated lupus phenotype in mice. Here, we explore the role of the endogenous ACOD1/itaconate pathway in the development of murine lupus as well as their relevance in premature cardiovascular damage in SLE. Methods
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Hip shape shows a causal effect on hip fracture but not hip osteoarthritis: findings from a GWAS meta-analysis and causal analyses medRxiv. Rheumatol. Pub Date : 2024-01-26 Benjamin G Faber, Monika Frysz, Jiayi Zheng, Huandong Lin, Kaitlyn Flynn, Raja Ebsim, Fiona R Saunders, Rhona A Beynon, Jenny S Gregory, Richard M Aspden, Nicholas C Harvey, Claudia Lindner, Tim Cootes, David Evans, George Davey Smith, Xin Gao, Sijia Wang, John Kemp, Jon Tobias
Objectives Hip shape is thought to be an important causal risk factor for hip osteoarthritis and fracture. We aimed to identify genetic determinants of hip shape and use these to assess causal relationships with hip osteoarthritis. Methods Statistical hip shape modelling was used to derive 10 hip shape modes (HSMs) from DXA images in UK Biobank and Shanghai Changfeng cohorts (ntotal=43,485). Genome-wide
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Depression is a more significant predictor for wellbeing in Inclusion Body Myositis than physical disability. medRxiv. Rheumatol. Pub Date : 2024-01-23 Georgina Nunn, Genevieve Glenister, Kathryn Hird, Kelly Beer, Ian Cooper, Merrilee Needham
Objectives: (1) determine if there is a correlation between disability, depression, and wellbeing in people with IBM, (2) determine if disability and depression can predict wellbeing in people with IBM, and (3) identify the prevalence of depression and impaired wellbeing in participants with IBM. Methods: In this cross-sectional study, 101 participants with IBM completed the Neuromuscular Symptom Score
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Identification of disease-specific TCRs maintaining pathogenic T helper cell responses in postinfectious Lyme Arthritis medRxiv. Rheumatol. Pub Date : 2024-01-20 Johannes Dirks, Jonas Fischer, Julia Klaussner, Christine Hofmann, Annette Holl-Wieden, Viktoria Buck, Christian Klemann, Hermann Girschick, Ignazio Caruana, Florian Erhard, Henner Morbach
Background Antibiotic-Refractory Lyme Arthritis(ARLA) involves a complex interplay of T cell responses targeting Borrelia burgdorferi antigens succeeding towards autoantigens by epitope spreading. However, the precise molecular mechanisms driving the pathogenic T cell response in ARLA remain unclear. Our aim was to elucidate the molecular program of disease-specific Th cells.
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Endogenous retroelement activation is implicated in IFN-α production and anti-CCP autoantibody generation in early RA medRxiv. Rheumatol. Pub Date : 2024-01-20 Faye AH Cooles, Gemma V Pedrola, Najib Naamane, Arthur G Pratt, Ben Barron-Millar, Amy E Anderson, Catharien MU Hilkens, John Casement, Vincent Bondet, Darragh Duffy, Fan Zhang, Ruchi Shukla, John D Isaacs
Objectives Endogenous retroelements (EREs) stimulate type 1 interferon (IFN-I) production but have not been explored as potential interferonogenic triggers in Rheumatoid Arthritis (RA). We investigated ERE expression in early RA (eRA), a period where IFN-I is increased.
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Analysis of dietary vitamin C intake levels and the risk of hyperuricemia and gout based on cross-sectional studies and bi-directional Mendelian randomisation medRxiv. Rheumatol. Pub Date : 2024-01-18 Zi-Ning Peng, Xing-Qiang Wang, Qian Deng, Wei-Tian Yan, Wei-Qing Zhao, Yong-Bin Pu, Nian Liu, Ling-Li Gu, Jiang-Yun Peng
Background Vitamin C, a common antioxidant, may be useful for treating hyperuricemia and gout. The aim of this study was to investigate the risk association between dietary vitamin C intake and hyperuricemia/gout and to test for causality using the bi-directional Mendelian randomisation method.
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Pathogenic autoantibody internalization in myositis medRxiv. Rheumatol. Pub Date : 2024-01-17 Iago Pinal-Fernandez, Sandra Muñoz-Braceras, Maria Casal-Dominguez, Katherine Pak, Jiram Torres-Ruiz, Jon Musai, Stefania Dell’Orso, Faiza Naz, Shamima Islam, Gustavo Gutierrez-Cruz, Maria Dolores Cano, Ana Matas-Garcia, Joan Padrosa, Esther Tobías-Baraja, Gloria Garrabou, Iban Aldecoa, Gerard Espinosa, Carmen Pilar Simeon-Aznar, Alfredo Guillen-Del-Castillo, Albert Gil-Vila, Ernesto Trallero-Araguas
Objectives Myositis is a heterogeneous family of autoimmune muscle diseases. As myositis autoantibodies recognize intracellular proteins, their role in disease pathogenesis has been unclear. This study aimed to determine whether myositis autoantibodies reach their autoantigen targets within muscle cells and disrupt the normal function of these proteins.
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cg05883128 (DDX60) and NR3C2 (CD4 T-cells and B-cells) to Be the Genetic Roots of Systemic Lupus Erythematosus medRxiv. Rheumatol. Pub Date : 2024-01-17 Zhengjun Zhang
Motivation Systemic lupus erythematosus (SLE) is an autoimmune disease and a long-term condition affecting many body parts. Autoimmune diseases are affecting more people for reasons unknown, and the causes of these diseases remain a mystery.
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Antiphospholipid antibodies exacerbate damage following oxygen deprivation-reperfusion injury in an in vivo model for stroke and in ex vivo blood derived endothelial cells medRxiv. Rheumatol. Pub Date : 2024-01-07 Charis Pericleous, Daniel J. Stuckey, Robert T. Maughan, Koralia Paschalaki, Lida Kabir, Lauren T. Bourke, Rohan Willis, Anisur Rahman, Anna M. Randi, Deepa J. Arachchillage, Mark Lythgoe, Ian P. Giles, Justin C. Mason, Yiannis Ioannou
Background Prothrombotic antiphospholipid antibodies (aPL) found in patients with antiphospholipid syndrome (APS) are a recognised risk factor for ischemic stroke. However, it is unclear if aPL cause injury post thrombolysis leading to worse outcomes. We investigated whether aPL exacerbate reperfusion injury and sought to translate our findings in endothelial colony forming cells (ECFC) isolated from
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Effect of shared decision-making on trust in physicians in the management of systemic lupus erythematosus: The TRUMP2-SLE prospective cohort study medRxiv. Rheumatol. Pub Date : 2024-01-07 Ryusuke Yoshimi, Nobuyuki Yajima, Chiharu Hidekawa, Natsuki Sakurai, Nao Oguro, Kenta Shidahara, Keigo Hayashi, Takanori Ichikawa, Dai Kishida, Yoshia Miyawaki, Ken-ei Sada, Yasuhiro Shimojima, Yuichi Ishikawa, Yuji Yoshioka, Yosuke Kunishita, Daiga Kishimoto, Kaoru Takase-Minegishi, Yohei Kirino, Shigeru Ohno, Noriaki Kurita, Hideaki Nakajima
Objectives Few studies have explored whether the involvement of patients in shared decision-making (SDM) is beneficial to the management of systemic lupus erythematosus (SLE). Therefore, this study investigated the relationship between patient participation in SDM and their trust in physicians using data from the TRUMP2-SLE study.
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Risk-stratified monitoring for sulfasalazine toxicity: prognostic model development and validation. medRxiv. Rheumatol. Pub Date : 2023-12-18 Abhishek Abhishek, Matthew J Grainge, Tim Card, Hywel C Williams, Maarten W Taal, Guruprasad P Aithal, Christopher P Fox, Christian D Mallen, Matthew D Stevenson, Georgina Nakafero, Richard D Riley
Background: Sulfasalazine induced cytopenia, nephrotoxicity, and hepatotoxicity is uncommon during long-term treatment. Some guidelines recommend three monthly monitoring blood-tests indefinitely while others recommend stopping monitoring after one year. To rationalise monitoring we developed and validated a prognostic model for clinically significant blood, liver, or kidney toxicity during established
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Trends in Efficacy, Safety, and Tolerability of Approved Multiple Sclerosis Disease Modifying Treatments medRxiv. Rheumatol. Pub Date : 2023-12-11 Kyle Valker, Kangho Suh
Background Disease-modifying therapies (DMTs) have become the mainstay of treatment for relapsing forms of multiple sclerosis (MS), reducing relapse rates and slowing disease progression.
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Haloperidol inhibits inflammasome activation via LAMTOR1 and reduces the risk of arthritides medRxiv. Rheumatol. Pub Date : 2023-12-08 Vidya Ambati, Praveen Yerramothu, Ranjith Konduri, Joseph Nguyen, Bradley D Gelfand, Brian C Werner, Ethan W Taylor, Shao-bin Wang
Gout is the most prevalent form of inflammatory arthritis in the world. Although multiple treatments exist, many patients are poorly responsive. Here we report, using a health insurance database analysis, that use of the anti-psychotic haloperidol is associated with a reduced risk of incident gout. Haloperidol inhibits ASC speck formation, caspase-1 activation, and release of IL-1beta; and IL-6, suggesting
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Improvements and challenges of long-term survival in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension: A 10-year multi-center cohort study medRxiv. Rheumatol. Pub Date : 2023-12-07 Xingbei Dong, Jiuliang Zhao, Junyan Qian, Wei Wei, Miaojia Zhang, Xiao Zhang, Xiaofei Shi, Yisha Li, Xiaoping Hong, Qiang Shu, Shuhong Chi, Xin Dong, Ping Zhu, Rong Zhang, Zhuoli Zhang, Hongfeng feng Zhang, Xinwang Duan, Jing Xue, Shuhong Zhou, Hongbin Li, Dan Chen, Junwei Zhang, Yanhong WANG, Zhuang Tian, Yong-Tai Liu, Mengtao Li, Xiaofeng ZENG, Qian Wang
Background: Prior studies indicated improved survival in systemic sclerosis-associated pulmonary arterial hypertension (PAH) patients, but trends in systemic lupus erythematosus-associated PAH (SLE-PAH) survival remained unclear. Methods: Analyzing SLE-PAH patients from the nationwide CSTAR-PAH cohort, we divided them into two cohorts: A (2011-2016) and B (2016-2021), based on baseline right heart
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A genome-wide association study suggests new susceptibility loci for primary antiphospholipid syndrome medRxiv. Rheumatol. Pub Date : 2023-12-05 Desire Casares-Marfil, Manuel Martinez-Bueno, Maria Orietta Borghi, Guillermo Pons-Estel, PRECISESADS Clinical Consortium, Guillermo Reales, Yu Zuo, Gerard Espinosa, Timothy R.D.J. Radstake, Lucas L. van den Hoogen, Chris Wallace, Joel Guthridge, Judith James, Ricard Cervera, Pier Luigi Luigi Meroni, Javier Martín, Jason Knight, Marta Alarcon-Riquelme, Amr H Sawalha
Objectives: Primary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify novel genetic susceptibility loci associated with PAPS. Methods: We performed a genome-wide association study comprising 5,485 individuals (482 affected individuals)
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PFKFB3 is a critical regulator of neutrophil metabolism and function in rheumatoid arthritis medRxiv. Rheumatol. Pub Date : 2023-12-03 Michele Fresneda Alarcon, Genna Ali Abdullah, Andrew H Nolan, Christina Linford, Marie M Phelan, Helen L Wright
Neutrophils are key effector leukocytes of the innate immune system and play a pivotal role in defending the host against microbial infections. Recent studies have identified a crucial link between glycolysis and neutrophil cellular functions. Using human neutrophils, we have investigated the intricate relationship between glycolysis, extracellular glucose availability, and the enzyme 6-phosphofru
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Prodromal symptoms of rheumatoid arthritis in a primary care database: variation by ethnicity and socioeconomic status medRxiv. Rheumatol. Pub Date : 2023-11-15 Alexander d'Elia, Aliaksandra Baranskaya, Shamil Haroon, Ben Hammond, Nicola J Adderley, Krishnaraja Nirantharakumar, Joht Singh Chandan, Marie Falahee, Karim Raza
Objectives To assess whether prodromal symptoms of rheumatoid arthritis (RA), as recorded in the Clinical Practice Research Datalink Aurum (CPRD) database of English primary care records, differ by ethnicity and socioeconomic status. Methods A cross-sectional study to determine the coding of common symptoms (≥0.1 % in the sample) in the 24 months preceding RA diagnosis in CPRD Aurum, recorded between
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Factors influencing the outcomes of non-pharmacological interventions for managing fatigue across the lifespan of people living with musculoskeletal (MSK) conditions: a scoping review protocol medRxiv. Rheumatol. Pub Date : 2023-11-15 Katie Fishpool, George Young, Coziana Ciurtin, Fiona Cramp, Emmanuel Erhieyovwe, Bayram Farisogullari, Gary J Macfarlane, Pedro Machado, Jennifer Pearson, Eduardo Santos, Emma Dures
Introduction Fatigue is an important and distressing symptom for many people living with chronic musculoskeletal (MSK) conditions. Many non-pharmacological interventions have been investigated in recent years and some have been demonstrated to be effective in reducing fatigue and fatigue impact, however there is limited guidance for clinicians to follow regarding the most appropriate management options
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Analysis of 245,368 diverse individuals from the NIH All of Us Cohort identifies incomplete penetrance of the VEXAS-defining UBA1 p.M41L somatic mutation medRxiv. Rheumatol. Pub Date : 2023-11-08 Robert W Corty, Kevin W Byram, Jason M Springer, Peter C Grayson, Alexander G Bick
Objective: Somatic mutations in UBA1 cause the recently described systemic auto-inflammatory syndrome, VEXAS. Study of this disease has largely been limited to highly symptomatic patients. We sought to determine the prevalence of VEXAS-associated somatic mutations and their disease penetrance in a diverse, unselected population. Methods: We analyzed clinical-grade whole genome sequencing data from
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A randomised controlled trial of the effect of intra-articular lidocaine on pain scores in inflammatory arthritis medRxiv. Rheumatol. Pub Date : 2023-10-30 Zoe Rutter-locher, Sam Norton, Fran Denk, Stephen McMahon, Leonie S Taams, Kirsty Bannister, Bruce W Kirkham
Background: Chronic pain in inflammatory arthritis (IA) reflects a complex interplay between active disease in a peripheral joint and central pro-nociceptive mechanisms. Since intra-articular lidocaine may be used to abolish joint-specific peripheral input to the central nervous system, we aimed to validate its use as a clinical tool to identify those IA patients whose pain likely incorporates centrally
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Digital health technologies and machine learning augment patient reported outcomes to remotely characterise rheumatoid arthritis medRxiv. Rheumatol. Pub Date : 2023-10-27 Andrew P. Creagh, Valentin Hamy, Hang Yuan, Gert Mertes, Ryan Tomlinson, Wen-Hung Chen, Rachel Williams, Christopher Llop, Christopher Yee, Mei Sheng Duh, Aiden Doherty, Luis Garcia-Gancedo, David A. Clifton
Digital measures of health status captured during daily life could greatly augment current in-clinic assessments for rheumatoid arthritis (RA), to enable better assessment of disease progression and impact. This work presents results from weaRAble-PRO, a 14-day observational study, which aimed to investigate how digital health technologies (DHT), such as smartphones and wearables, could augment patient
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A SYSTEMATIC REVIEW : CARDIOVASCULAR EFFECTS OF SYSTEMIC SCLEROSIS medRxiv. Rheumatol. Pub Date : 2023-10-20 BINAY KUMAR PANJIYAR, Dedeepya Panchumarthi, SASIDHAR BATHULA, SAI TAPASVI MADAM, Raghu Ram Shanmukh Nemani
Systemic sclerosis is a connective autoimmune disorder characterized by the deposition of an extracellular matrix in the internal organs leading to fibrosis and damage to internal organs.Cardiovascular effects of systemic sclerosis include arrhythmias,coronary artery disease,valvular diseases,pericardial diseases,atherosclerosis,myocardial diseases .Thus it also has a fatal effect on the cardiovascular
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Immunomodulators and risk for breakthrough infection after third COVID-19 mRNA vaccine among patients with rheumatoid arthritis: A cohort study medRxiv. Rheumatol. Pub Date : 2023-10-09 Abigail E. Schiff, Xiaosong Wang, Naomi J. Patel, Yumeko Kawano, Emily N. Kowalski, Claire E. Cook, Kathleen M.M. Vanni, Grace Qian, Katarina J. Bade, Alene A. Saavedra, Shruthi Srivatsan, Zachary K. Williams, Rathnam K. Venkat, Zachary S. Wallace, Jeffrey A. Sparks
Objectives: To investigate COVID-19 breakthrough infection after third mRNA vaccine dose among patients with RA by immunomodulator drug class, and we hypothesized that CD20 inhibitors (CD20i) would have higher risk for breakthrough COVID-19 vs. TNF inhibitors (TNFi). Methods: We performed a retrospective cohort study investigating breakthrough COVID-19 among RA patients at Mass General Brigham in Boston
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Functional genomics implicates natural killer cells as potential key drivers in the pathogenesis of ankylosing spondylitis medRxiv. Rheumatol. Pub Date : 2023-09-26 Marcos Chinas, Daniela Fernandez-Salinas, Vitor RC Aguiar, Victor E Nieto-Caballero, Micah Lefton, Peter A Nigrovic, Joerg Ermann, Maria Gutierrez-Arcelus
Objective: Multiple lines of evidence indicate that ankylosing spondylitis (AS) is a lymphocyte-driven disease. However, which lymphocyte populations are critical in AS pathogenesis is not known. In this study, we aimed to identify the key cell types mediating the genetic risk in AS using an unbiased integrative functional genomics approach. Methods: We integrated GWAS data with epigenomic and transcriptomic
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Reliability, validity, and sensitivity of Japanese version of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument: application to efficacy assessment of intravenous immunoglobulin administration. medRxiv. Rheumatol. Pub Date : 2023-09-20 Kazuki Mitsuru Matsuda, Eiki Sugimoto, Yoshiaki Ako, Marie Kitamura, Mai Miyahara, Hirohito Kotani, Yuta Norimatsu, Teruyoshi Hisamoto, Ai Kuzumi, Takemichi Fukasawa, Shinichi Sato, Ayumi Yoshizaki
Objective This study aimed to develop and assess the reliability, validity, and sensitivity of Japanese version of the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (GIT) Instrument 2.0 (the GIT score), as an evaluation tool for GIT symptoms in systemic sclerosis (SSc). Methods Japanese version of the GIT score was constructed using the forward-backward
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IMBALANCED MACHINE LEARNING CLASSIFICATION MODELS FOR REMOVAL BIOSIMILAR DRUGS AND INCREASED ACTIVITY IN PATIENTS WITH RHEUMATIC DISEASES medRxiv. Rheumatol. Pub Date : 2023-09-11 David Castro Corredor, Luis Ángel Calvo Pascual
Objective Predict long-term disease worsening and the removal of biosimilar medication in patients with rheumatic diseases.
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Novel autoantibodies help diagnose anti-SSA antibody negative Sjogrens disease and predict abnormal labial salivary gland pathology medRxiv. Rheumatol. Pub Date : 2023-08-29 Maxwell Parker, Zihao Zheng, Michael Lasarev, Roxana A Alexandridis, Michael A Newton, Miriam A Shelef, Sara S McCoy
Objectives: Sjogrens disease (SjD) diagnosis requires either positive anti-SSA antibodies or a labial salivary gland biopsy with a positive focus score (FS). One-third of SjD patients lack anti-SSA antibodies (SSA-), requiring a positive FS for diagnosis. Our objective was to identify novel autoantibodies to diagnose seronegative SjD. Methods: IgG binding to a high density whole human peptidome array
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Uncoupling interferons and the interferon signature explain clinical and transcriptional subsets in SLE medRxiv. Rheumatol. Pub Date : 2023-08-28 Eduardo Gomez-Banuelos, Daniel W Goldman, Victoria Andrade, Erika Darrah, Michelle Petri, Felipe Andrade
Interferons (IFN) are thought to be key players in systemic lupus erythematosus (SLE). The unique and interactive roles of the different IFN families in SLE pathogenesis, however, remain poorly understood. Using reporter cells engineered to precisely quantify IFN-I, IFN-II and IFN-III activity levels in serum/plasma, we found that while IFNs play essential role in SLE pathogenesis and disease activity
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ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon medRxiv. Rheumatol. Pub Date : 2023-08-28 Sylvia Hartmann, Summaira Yasmeen, Benjamin M Jacobs, Spiros Denaxas, Munir Pirmohamed, Eric R. Gamazon, Mark J Caulfield, Harry Hemingway, Maik Pietzner, Claudia Langenberg
Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk
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Characterising the neurobiological mechanisms of action of exercise and cognitive behavioural interventions for rheumatoid arthritis fatigue: an MRI brain study medRxiv. Rheumatol. Pub Date : 2023-08-24 Amir Dehsarvi, Salim Al-Wasity, Kristian Stefanov, Stewart Wiseman, Stuart Ralston, Joanna M Wardlaw, Richard Emsley, Eva-maria Bachmair, Jonathan Cavanagh, Gordon D. Waiter, Neil Basu
Background: Chronic Fatigue is a major clinical unmet need among patients with Rheumatoid Arthritis (RA). Current therapies are limited to non-pharmacological interventions, such as personalised exercise programmes (PEP) and cognitive behavioural approaches (CBA), however, still most patients continue to report severe fatigue. To inform more effective therapies, we conducted an MRI brain study of PEP
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Factors Associated with Physical Function among People with Systemic Sclerosis: A Scleroderma Patient-centered Intervention Network (SPIN) Cohort Cross-sectional Study medRxiv. Rheumatol. Pub Date : 2023-08-24 Tiffany Dal Santo, Danielle B Rice, Marie-Eve Carrier, Gabrielle Virgili-Gervais, Brooke Levis, Linda Kwakkenbos, Susan J Bartlett, Amy Gietzen, Karen Gottesman, Genevi Guillot, Marie Hudson, Laura K Hummers, Vanessa L Malcarne, Maureen D Mayes, Luc Mouthon, Michelle Richard, Maureen Sauv, Robyn K Wojeck, Marie-Claude Geoffroy, Andrea Benedetti, Brett Thombs
Objectives: To compare physical function in systemic sclerosis (SSc, scleroderma) to general population normative data and identify associated factors. Methods: Scleroderma Patient-centered Intervention Network Cohort participants completed the Physical Function domain of the Patient-Reported Outcomes Measurement Information System Version 2 upon enrollment. Multivariable linear regression was used
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Computer vision detects inflammatory arthritis in standardized smartphone photographs in an Indian patient cohort medRxiv. Rheumatol. Pub Date : 2023-08-22 Sanat Phatak, Somashree Chakraborty, Pranay Goel
Introduction: Computer vision extracts meaning from pixelated images and holds promise in automating clinical tasks. Convolutional neural networks (CNN), deep learning networks used therein, have shown promise in X-ray images as well as joint photographs. We studied the performance of a CNN on standardized smartphone photographs in detecting inflammation in three hand joints. Methods: We enrolled consecutive
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Inhibition of JAK-STAT pathway corrects salivary gland inflammation and interferon driven immune activation in Sjögren's Disease medRxiv. Rheumatol. Pub Date : 2023-08-21 Blake Matthew Warner, Sarthak Gupta, Eiko Yamada, Hiroyuki Nakamura, Paola Perez, Thomas J.F. Pranzatelli, Kalie Dominick, Shyh-Ing Jang, Mehdi Abed, Dani Martin, Peter Burbelo, Changyu Zheng, Ben French, Ilias Alevizos, Zohreh Khavandgar, Margaret Beach, Eileen Pelayo, Brian Walitt, Sarfaraz Hasni, Mariana Kaplan, Mayank Tandon, M. Teresa Magone, David Kleiner, Jay Chiorini, Alan Baer
Objectives: Inflammatory cytokines that signal through the JAK- STAT pathway, especially interferons (IFNs), are implicated in Sjogrens Disease (SjD). Although inhibition of JAKs is effective in other autoimmune diseases, a systematic investigation of IFN-JAK-STAT signaling and effect of JAK inhibitor (JAKi) therapy in SjD-affected human tissues has not been reported. Methods: Human minor salivary
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Methodological development of molecular endotype discovery from synovial fluid of individuals with knee osteoarthritis: the STEpUP OA Consortium medRxiv. Rheumatol. Pub Date : 2023-08-16 Yun Deng, Thomas A Perry, Philippa Hulley, Rose A Maciewicz, Joanna Mitchelmore, Darryl Perry, Staffan Larsson, Sophie Brachat, André Struglics, C Thomas Appleton, Stefan Kluzek, Nigel K Arden, David Felson, Brian Marsden, Brian D M Tom, Laura Bondi, Mohit Kapoor, Vicky Batchelor, Jennifer Mackay-Alderson, Vinod Kumar, L Stefan Lohmander, Tim J Welting, David A Walsh, Ana M Valdes, STEpUP OA Consortium
Objectives: To develop and validate a pipeline for quality controlled (QC) protein data for largescale analysis of synovial fluid (SF), using SomaLogic technology. Design: Knee SF and associated clinical data were from partner cohorts. SF samples were centrifuged, supernatants stored at -80oC, then analysed by SomaScan Discovery Plex V4.1 (>7000 SOMAmers/proteins). Setting: An international consortium
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ANTI-CITRULLINATED ALBUMIN ANTIBODIES AS BIOMARKER FOR THE DIAGNOSIS OF RHEUMATOID ARTHRITIS medRxiv. Rheumatol. Pub Date : 2023-08-10 Vishnupriya R Paturi, Ramakrishna R Uppuluri, Lina Gao, Charles T Roberts, SRINIVASA NAGALLA
Objective: Citrullinated human serum albumin has been previously reported in serum and synovial fluid from individuals with rheumatoid arthritis (RA), and antibodies to citrullinated human serum albumin (ACA) have been identified in RA serum. We developed a point-of-care (POC) test for ACA and evaluated its sensitivity and specificity in healthy subjects and subjects with clinically diagnosed RA and
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Harnessing ChatGPT and GPT-4 for Evaluating the Rheumatology Questions of the Spanish Access Exam to Specialized Medical Training medRxiv. Rheumatol. Pub Date : 2023-08-07 Alfredo Madrid-García, Zulema Rosales-Rosado, Dalifer Dayanira Freites-Núñez, Inés Pérez-Sancristobal, Esperanza Pato-Cour, Chamaida Plasencia-Rodríguez, Luis Cabeza-Osorio, Lydia Abasolo Alcazar, Leticia Leon Mateos, Benjamín Fernández-Gutiérrez, Luis Rodríguez-Rodríguez
The emergence of Large Language Models (LLM) with remarkable performance such as ChatGPT and GPT-4, has led to an unprecedented uptake in the population. One of their most promising and studied applications concerns education due to their ability to understand and generate human-like text, creating a multitude of opportunities for enhancing educational practices and outcomes. The objective of this
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Somatic TET2 Mutations are Associated with Giant Cell Arteritis medRxiv. Rheumatol. Pub Date : 2023-07-31 Michelle L. Robinette, Lachelle D. Weeks, Ryan J. Kramer, Mridul Agrawal, Christopher J. Gibson, Zhi Yu, Aswin Sekar, Arnav Mehta, Abhishek Niroula, Jared T. Brown, Gregory C. McDermott, Edith R. Reshef, Jonathan E. Lu, Victor D. Liou, Carolina A. Chiou, Pradeep Natarajan, Suzanne K. Freitag, Deepak A. Rao, Benjamin A. Ebert
Objective Giant cell arteritis (GCA) is an age-related vasculitis of large and medium sized vessels. Prior studies have identified an association between GCA and hematologic malignancies (HM). How the presence of somatic mutations, which drive development of HM, or clonal hematopoiesis (CH), may influence clinical outcomes in GCA is not well understood. Methods: To examine an association between CH
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Common comorbidities in polymyalgia rheumatica and giant cell arteritis: cross-sectional study in UK Biobank medRxiv. Rheumatol. Pub Date : 2023-07-31 Charikleia Chatzigeorgiou, John C. Taylor, Faye Elliott, Eoin P O'Sullivan, UK Biobank Eye and Vision Consortium, Ann W Morgan, Jennifer H. Barrett, Sarah L. Mackie
Objective. To determine prevalent comorbidities in cases with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA) compared to matched controls. Methods. Nested, cross sectional case-control study within UK Biobank. Case status was defined as self-reported prior diagnosis of PMR or GCA. 10 controls per case were matched for age, sex, ethnicity and assessment centre. Associations with selected
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Multi-omics analysis in primary T cells elucidates mechanisms behind disease associated genetic loci medRxiv. Rheumatol. Pub Date : 2023-07-23 Chenfu Shi, Danyun Zhao, Stefano Rossi, Antonios Frantzeskos, James Ding, Carlo Ferrazzano, Charlotte Wynn, Ryan Hum, Ellie Richards, Muskan Gupta, Chuan Fu Yap, Darren Plant, Richard Grencis, Paul Martin, Antony Adamson, Stephen Eyre, John Bowes, Anne Barton, Pauline Ho, Magnus Rattray, Gisela Orozco
In this study, we present the most extensive dataset of chromatin conformation data with matching gene expression and chromatin accessibility from primary T cells to date. We use this data to enhance our understanding of the different mechanisms by which GWAS variants impact gene regulation and revealing how natural genetic variation alter chromatin accessibility and structure in primary cells at an
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Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis medRxiv. Rheumatol. Pub Date : 2023-07-18 Andrea Fava, Jill Buyon, Larry Magder, Jeffrey Hodgin, Avi Rosenberg, Dawit Demeke, Deepak A. Rao, Arnon Arazi, Alessandra Ida Celia, Chaim Putterman, Jennifer Anolik, Jennifer Barnas, Maria Dall'Era, David Wofsy, Richard Furie, Diane Kamen, Kenneth Kalunian, Judith James, Joel Guthridge, Mo Atta, Manny Monroy-Trujillo, Derek Fine, Robert Clancy, H. Michael Belmont, Peter Izmirly, William Apruzzese
Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic
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Autoantibodies to nuclear valosin-containing protein-like protein: identification and characterization of systemic sclerosis-related anti-nucleolar antibodies utilizing in vitro human proteome medRxiv. Rheumatol. Pub Date : 2023-07-18 Kazuki Mitsuru/M Matsuda, Hirohito Kotani, Kei Yamaguchi, Chihiro Ono, Taishi Okumura, Koji Ogawa, Ayako Miya, Ayaka Sato, Rikako Uchino, Yumi Murakami, Hiroshi Matsunaka, Masanori Kono, Yuta Norimatsu, Teruyoshi Hisamoto, Ruriko Kawanabe, Ai Kuzumi, Takemichi Fukasawa, Asako Yoshizaki-Ogawa, Tomohisa Okamura, Hurofumi Shoda, Keishi Fujio, Takashi Matsushita, Naoki Goshima, Shinichi Sato, Ayumi Yoshizaki
Objectives To identify and characterize undescribed systemic sclerosis (SSc)-related autoantibodies targeting nucleolar antigens and to assess their clinical significance. Methods We conducted proteome-wide autoantibody screening (PWAS) against serum samples from SSc patients with nucleolar patterned anti-nuclear antibodies (NUC-ANAs) of specific antibodies (Abs) unknown, utilizing wet protein arrays
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Metabolic signature and proteasome activity controls synovial migration of CDC42hiCD14+ cells in rheumatoid arthritis medRxiv. Rheumatol. Pub Date : 2023-06-16 Eric Malmhall-Bah, Karin M.E. Andersson, Malin Erlandsson, Sofia T. Silfversward, Rille Pullerits, Maria I Bokarewa
Objective: Activation of Rho-GTPases in macrophages causes inflammation and severe arthritis in mice. In this study, we explore if Rho-GTPases define the joint destination of pathogenic leukocytes in rheumatoid arthritis (RA) and how JAK inhibition mitigates these effects. Methods: CD14+ cells of 136 RA patients were characterized by RNA-sequencing, and cytokine measurement to identify biological processes
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Spondyloarthritis, acute anterior uveitis, and Crohn’s disease have both shared and distinct gut microbiota medRxiv. Rheumatol. Pub Date : 2023-05-28 Morgan Essex, Valeria Rios Rodriguez, Judith Rademacher, Fabian Proft, Ulrike Löber, Lajos Markó, Uwe Pleyer, Till Strowig, Jérémy Marchand, Jennifer A. Kirwan, Britta Siegmund, Sofia Kirke Forslund, Denis Poddubnyy
Objectives Spondyloarthritis (SpA) is a group of immune-mediated diseases highly concomitant with non-musculoskeletal inflammatory disorders, such as acute anterior uveitis (AAU) and Crohn’s disease (CD). The gut microbiome represents a promising avenue to elucidate shared and distinct underlying pathophysiology.
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The impact of attending rheumatologist’s Big Five personality traits on systemic lupus erythematosus patients’ trust in their rheumatologist: the TRUMP2-SLE project medRxiv. Rheumatol. Pub Date : 2023-05-28 Nao Oguro, Nobuyuki Yajima, Yuichi Ishikawa, Natsuki Sakurai, Chiharu Hidekawa, Takanori Ichikawa, Dai Kishida, Keigo Hayashi, Kenta Shidahara, Yoshia Miyawaki, Ryusuke Yoshimi, Ken-ei Sada, Yasuhiro Shimojima, Noriaki Kurita
Objectives Differences in communication styles according to physicians’ personality traits have been identified, and such physician-related factors can be important in building patient-physician trust. This study examined the impact of rheumatologists’ Big Five personality traits on patients’ trust in their attending rheumatologists.
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Refractory Inflammatory Arthritis definition and model generated through patient and multi-disciplinary professional modified Delphi process medRxiv. Rheumatol. Pub Date : 2023-05-26 Hema Chaplin, Ailsa Bosworth, Carol Simpson, Kate Wilkins, Jessica Meehan, Elena Nikiphorou, Rona Moss- Morris, Heidi Lempp, Sam Norton
Objective Various definitions have been proposed for Refractory Disease in people with Rheumatoid Arthritis; however, none were generated for Polyarticular Juvenile Idiopathic Arthritis or involving adult and paediatric multidisciplinary healthcare professionals and patients. The study aim is to redefine Refractory Disease, using Delphi methodology.
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Automated multi-scale computational pathotyping (AMSCP) of inflamed synovial tissue medRxiv. Rheumatol. Pub Date : 2023-05-25 Richard D. Bell, Matthew Brendel, Maxwell Konnaris, Justin Xiang, Miguel Otero, Mark A. Fontana, Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Edward DiCarlo, Jennifer Anolik, Laura Donlin, Dana Orange, H. Mark Kenney, Edward M. Schwarz, Lionel B Ivashkiv, Fei Wang
Rheumatoid arthritis (RA) is a complex immune-mediated inflammatory disorder in which patients suffer from inflammatory-erosive arthritis. Recent advances on histopathology heterogeneity of RA pannus tissue revealed three distinct phenotypes based on cellular composition (pauci-immune, diffuse and lymphoid), suggesting distinct etiologies that warrant specific targeted therapy. Thus, cost-effective
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Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis medRxiv. Rheumatol. Pub Date : 2023-05-23 Sizheng Steven Zhao, Amy Mason, Eva Gjekmarkaj, Haruyuki Yanaoka, Stephen Burgess
Objective The VITAL trial of vitamin D supplementation suggested a possible protective effect for autoimmune diseases but uncertainties remain. We investigated potential causal effects of vitamin D on composite and individual autoimmune diseases using Mendelian randomization.
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The stool microbiome in patients with psoriatic arthritis is altered but, unlike the skin microbiome, does not change following treatment: evidence for an underlying inflammatory drive from the intestine medRxiv. Rheumatol. Pub Date : 2023-05-21 Madhura Castelino, Umer Z Ijaz, Mauro Tutino, Elizabeth MacDonald, George E. Fragoulis, Pauline Ho, Devesh Mewar, Gladston Chelliah, Andrew McBain, Catherine O’Neill, Stefan Siebert, Anne Barton, Simon Milling
Objectives There is growing recognition that interactions between bacteria and the immune response may contribute to inflammation in psoriatic arthritis (PsA). To identify how the skin and stool microbiota may contribute to pathogenesis, we analysed the microbiota and immunophenotype of patients with PsA before and after therapy.
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Quantification of joint mobility limitation in adult type 1 diabetes medRxiv. Rheumatol. Pub Date : 2023-05-14 Sanat Phatak, Pranav Mahadevkar, Kaustubh Chaudhari, Shreya Chakladar, Swasti Jain, Smita Dhadge, Sarita Jadhav, Rucha Wagh, Rohan Shah, Aboli Bhalerao, Anupama Patil, Jennifer Ingram, Pranay Goel, Chittaranjan Yajnik
Background Diabetic cheiroarthropathies consist of limited joint mobility (LJM), flexor tenosynovitis (FTS), Dupuytren’s contracture (DC), and carpal tunnel syndrome (CTS). There is heterogeneity in definitions and lack of a method to measure hand fibrosis load. We measured metacarpophalangeal (MCP) joint restriction and describe magnetic resonance (MR) imaging characteristics across the spectrum of
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Genetic dissection of HLA-DRB1*15:01 and XL9 region variants in Japanese patients with systemic lupus erythematosus: Primary role for HLA-DRB1*15:01 medRxiv. Rheumatol. Pub Date : 2023-05-11 Aya Kawasaki, Premita Ari Kusumawati, Yuka Kawamura, Yuya Kondo, Makio Kusaoi, Hirofumi Amano, Yasuyoshi Kusanagi, Kenji Itoh, Takashi Fujimoto, Naoto Tamura, Hiroshi Hashimoto, Isao Matsumoto, Takayuki Sumida, Naoyuki Tsuchiya
Objective Major histocompatibility complex strongly contributes to susceptibility to systemic lupus erythematosus (SLE). In the European populations, HLA-DRB1*03:01 and DRB1*15:01 are susceptibility alleles, but C4 locus was reported to account for the association of DRB1*03:01. With respect to DRB1*15:01, strong linkage disequilibrium (LD) with a variant rs2105898T in the XL9 region, located between
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Associations between rheumatoid arthritis clinical factors with synovial cell types and states medRxiv. Rheumatol. Pub Date : 2023-05-04 Dana Weisenfeld, Fan Zhang, Laura Donlin, Anna Helena Jonsson, William Apruzzese, Debbie Campbell, Accelerating Medicines Partnership Program: Rheumatoid Arthritis Network, V. Michael Holers, Ellen Gravallese, Larry Moreland, Susan Goodman, Michael Brenner, Soumya Raychaudhuri, Andrew Filer, Jennifer Anolik, Vivian Bykerk, Katherine P. Liao
Objective Recent studies have uncovered diverse cell types/states in the RA synovium; however limited data exist correlating these findings with patient-level clinical information. Using the largest cohort to date with clinical and multi-cell data, we determined associations between RA clinical factors with cell types/states in the RA synovium.
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Diagnostic accuracy of MRI in diagnosing Cardiac Sarcoidosis - A Meta-analysis medRxiv. Rheumatol. Pub Date : 2023-05-04 Naqeeya Mustafa Sabuwala, Dwija Raval, Hetvi Parikh, Falak Saiyed, Dev Desai
Introduction A multisystem inflammatory illness-sarcoidosis is characterized by organ failure, noncaseating granuloma development, and inflammation. The most frequently affected tissues are the lungs and pulmonary lymph nodes, although other tissues can also be affected including the heart. Cardiac Sarcoidosis can be lethal and result in conduction abnormalities, arrhythmias, and sudden cardiac death
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Estimating overdiagnosis in giant cell arteritis diagnostic pathways using genetic data: genetic association study medRxiv. Rheumatol. Pub Date : 2023-04-24 Charikleia Chatzigeorgiou, Jennifer H Barrett, Javier Martin, UK GCA Consortium, Ann W Morgan, Sarah L Mackie
Objectives Prompt diagnosis of giant cell arteritis (GCA) is important to avert visual loss. False-negative temporal artery biopsy (TAB) can occur. Without vascular imaging, GCA may be overdiagnosed in TAB-negative cases, but it is unclear how often this occurs. An unbiased test is a way to address an imperfect reference standard. We used the known Human Leukocyte Antigen (HLA) region genetic association
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Rheumatoid Arthritis and Sarcopenia - a Prospective Single Center Cohort Study of Postmenopausal Women medRxiv. Rheumatol. Pub Date : 2023-04-23 Simeon Schietzel, Matthias B. Moor, Flurina Roos, Odile Stalder, Daniel Aeberli
Objectives The individual and socioeconomic burden of sarcopenia in rheumatoid arthritis (RA) is most relevant. However, longitudinal cohort data are scarce.
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Inflammation induced epigenetic activation of bivalent genes in osteoarthritic cartilage medRxiv. Rheumatol. Pub Date : 2023-04-20 Hao Du, Yao Zhang, Xi Yu, Xuanhe You, Diwei Wu, Zhenyu Luo, Yongrui Cai, Hanpeng Lu, Zhixin Liao, Bi-Sen Ding, Ya Zhao, Yan Wang, Ke Xiao, Fan Yang, Fangji Gan, Ning Ning, Jiancheng Zeng, Zongke Zhou, Shishu Huang
Osteoarthritis (OA) is the most prevalent joint disorder occurring with articular cartilage degradation, which includes a switch from an articular to a growth-plate chondrocyte phenotype. Epigenetics serves as a new therapeutic target but histone modification changes in OA remain elusive. Here, we investigated the profiles of four histone modifications in normal and OA chondrocytes. The repressive