Dysregulated NUB1 and Neddylation Enhances Rheumatoid Arthritis Fibroblast‐Like Synoviocyte Inflammatory Responses
Wiley Online Library » Arthritis & Rheumatology
by Sho Sendo, Camilla R. L. Machado, David L. Boyle, Robert J. Benschop, Narayanan B. Perumal, Eunice Choi, Wei Wang, Gary S. Firestein
1w ago
Objective Fibroblast-like synoviocytes (FLS) contribute to the pathogenesis of rheumatoid arthritis (RA), in part due to activation of the proinflammatory transcription factor NF-κB. Neddylation is modulated by the negative regulator of ubiquitin-like protein (NUB) 1. We determined whether NUB1 and neddylation are aberrant in the models with RA FLS, thereby contributing to their aggressive phenotype. Methods Models with RA or osteoarthritis (OA) FLS were obtained from arthroplasty synovia. Real-time quantitative polymerase chain reaction and Western blot analysis assessed gene and protein exp ..read more
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Amplified Type I Interferon Response in Sjögren's Disease via Ectopic Toll‐Like Receptor 7 Expression in Salivary Gland Epithelial Cells Induced by Lysosome‐Associated Membrane Protein 3
Wiley Online Library » Arthritis & Rheumatology
by Hiroyuki Nakamura, Tsutomu Tanaka, Changyu Zheng, Sandra A. Afione, Tatsuya Atsumi, Masayuki Noguchi, Fabiola Reis Oliveira, Ana Carolina F. Motta, Fernando Chahud, Eduardo M. Rocha, Blake M. Warner, John A. Chiorini
1w ago
Objective Lysosome-associated membrane protein 3 (LAMP3) misexpression in salivary gland epithelial cells plays a causal role in the development of salivary gland dysfunction and autoimmunity associated with Sjögren's disease (SjD). This study aimed to clarify how epithelial LAMP3 misexpression is induced in SjD. Methods To explore upstream signaling pathways associated with LAMP3 expression, we conducted multiple RNA sequencing analyses of minor salivary glands from patients with SjD, submandibular glands from a mouse model of SjD, and salivary gland epithelial cell lines. A hypothesis gener ..read more
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American College of Rheumatology White Paper: The Effects of Climate Change on Rheumatic Conditions—An Evolving Landscape and a Path Forward
Wiley Online Library » Arthritis & Rheumatology
by Paul F. Dellaripa, Lily H. Sung, Paul A. Bain, Cristina Lanata, Ashira Blazar, Frederick W. Miller, Candace H. Feldman, for the American College of Rheumatology Committee on Research
1w ago
Objective Increases in global temperatures and extreme weather events associated with climate change have complex yet poorly understood detrimental impacts on human health. We reviewed the current published literature on climate change–related effects and rheumatic conditions. Methods To summarize our current understanding of the likely effects of climate change, including increased air pollution, on rheumatic disease, we searched the published, peer-reviewed English-language literature from January 2000 to December 2022. Articles were reviewed by a team of rheumatologists and clinical and tra ..read more
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Hydroxychloroquine Dose and Hospitalizations for Active Lupus
Wiley Online Library » Arthritis & Rheumatology
by Jacquelyn Nestor, Hyon Choi, Christian Mancini, Baijun Zhou, Yuqing Zhang, Karen H. Costenbader, April Jorge
1w ago
Objectives We sought to determine the impact of hydroxychloroquine (HCQ) dose on the risk of hospitalizations for systemic lupus erythematosus (SLE). Methods We conducted a case-crossover study within an academic health system, including patients with SLE who used HCQ and had ≥ 1 hospitalization for active SLE between January 2011 and December 2021. Case periods ended in hospitalization for SLE, whereas control periods did not. The exposures were the average weight-based HCQ dose, categorized as ≤5 or >5 mg/kg/day, and non-weight-based HCQ dose, categorized as <400 or 400 mg/day, assesse ..read more
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Unique Interplay Between Antinuclear Antibodies and Nuclear Molecules in the Pathogenesis of Systemic Lupus Erythematosus
Wiley Online Library » Arthritis & Rheumatology
by David S. Pisetsky
1w ago
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that primarily affects young women and causes a wide range of inflammatory manifestations. The hallmark of SLE is the production of antibodies to components of the cell nucleus (antinuclear antibodies [ANAs]). These antibodies can bind to DNA, RNA, and protein complexes with nucleic acids. Among ANAs, antibodies to DNA (anti-DNA) are markers for classification and disease activity, waxing and waning disease activity in many patients. In the blood, anti-DNA antibodies can bind to DNA to form immune complexes with two distinct ..read more
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In This Issue
Wiley Online Library » Arthritis & Rheumatology
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1w ago
Arthritis &Rheumatology, Volume 76, Issue 6, June 2024 ..read more
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Predisposal of Interferon Regulatory Factor 1 Deficiency to Accumulate DNA Damage and Promote Osteoarthritis Development in Cartilage
Wiley Online Library » Arthritis & Rheumatology
by Yongsik Cho, Hyeonkyeong Kim, Geunho Yook, Sangmin Yong, Soy Kim, Narae Lee, Yi‐Jun Kim, Jin‐Hee Kim, Tae Woo Kim, Moon Jong Chang, Kyoung Min Lee, Chong Bum Chang, Seung‐Baik Kang, Jin‐Hong Kim
1w ago
Objective Interferon regulatory factor 1 (IRF1) is a transcriptional regulator conventionally associated with immunomodulation. Recent molecular analyses mapping DNA binding sites of IRF1 have suggested its potential function in DNA repair. However, the physiologic significance of this noncanonical function remains unexplored. Here, we investigated the role of IRF1 in osteoarthritis (OA), a condition marked by senescence and chronic joint inflammation. Methods OA progression was examined in wild-type and Irf1 −/− mice using histologic assessments and microcomputed tomography analysis of whole ..read more
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Screening of Environmental Chemicals to Characterize Exposures in Participants With Systemic Lupus Erythematosus
Wiley Online Library » Arthritis & Rheumatology
by Cristina M. Lanata, Kimberly E. Taylor, James Hurst‐Hopf, Joanne Nititham, Ashira Blazer, Laura Trupin, Patricia Katz, Maria Dall'Era, Jinoos Yazdany, Sharon A. Chung, Dimitri Abrahamsson, Roy Gerona, Lindsey A. Criswell
1w ago
Objective There is a need to characterize exposures associated with the pathogenesis of systemic lupus erythematosus (SLE). In this pilot study, we explore a hypothesis-free approach that can measure thousands of exogenous chemicals in blood (“exposome”) in patients with SLE and unaffected controls. Methods This cross-sectional study analyzed a cohort of patients with prevalent SLE (n = 285) and controls (n = 106). Plasma was analyzed by liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Mass spectrometry features present in at least 25% of all ..read more
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Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis–Associated Lymphoproliferative Disorders
Wiley Online Library » Arthritis & Rheumatology
by Yoshihiko Hoshida, Atsuko Tsujii, Shiro Ohshima, Yukihiko Saeki, Masato Yagita, Tomoya Miyamura, Masao Katayama, Tomonori Kawasaki, Yasushi Hiramatsu, Hisaji Oshima, Toshihiko Murayama, Shinji Higa, Kazuya Kuraoka, Fuminori Hirano, Kenji Ichikawa, Mitsutoshi Kurosawa, Hiroaki Suzuki, Noriyuki Chiba, Takao Sugiyama, Yuko Minami, Hitoshi Niino, Atsushi Ihata, Ikuo Saito, Akiko Mitsuo, Toshitaka Maejima, Atsuhiro Kawashima, Hiroshi Tsutani, Koichiro Takahi, Takahiko Kasai, Yoko Shinno, Yoshiro Tachiyama, Norihiro Teramoto, Kenichi Taguchi, Shinji Naito, Shigeru Yoshizawa, Masahiro Ito, Yasuo Suenaga, Shunsuke Mori, Shoichi Nagakura, Norie Yoshikawa, Mitsuharu Nomoto, Atsuhisa Ueda, Shouhei Nagaoka, Yukio Tsuura, Keigo Setoguchi, Shoji Sugii, Asami Abe, Toshiaki Sugaya, Hiroyuki Sugahara, Shigeki Fujita, Yasuo Kunugiza, Norishige Iizuka, Ryosuke Yoshihara, Hiroki Yabe, Tomoaki Fujisaki, Eiichi Morii, Morishige Takeshita, Masakazu Sato, Kazuyoshi Saito, Kiyoshi Matsui, Yasuhiko Tomita, Hiroshi Furukawa, Shigeto Tohma
1w ago
Objective In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). Methods In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. Results Overall, 752 patients with RA-associated ..read more
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VEXAS‐Defining UBA1 Somatic Variants in 245,368 Diverse Individuals in the NIH All Of Us Cohort
Wiley Online Library » Arthritis & Rheumatology
by Robert W. Corty, James Brogan, Kevin Byram, Jason Springer, Peter C. Grayson, Alexander G. Bick
1w ago
Objective Somatic variants in UBA1 cause VEXAS, a recently described, systemic autoinflammatory disease. Research on VEXAS has largely focused on highly symptomatic patients. We sought to determine the prevalence of canonical, VEXAS-associated somatic variants and their disease penetrance in a diverse, unselected population. Methods We analyzed clinical-grade whole genome sequencing data from 245,368 participants in the All of Us Research Program. We compared persons carrying a canonical VEXAS-associated somatic variant to age, sex, and ancestry matched controls across the domains of diagnose ..read more
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