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Arthritis Research & Therapy

James Bluett, Jamie C Sergeant, Alex J MacGregor, Jacqueline R Chipping, Tarnya Marshall, Deborah P M Symmons, Suzanne M M Verstappen
BACKGROUND: Oral methotrexate (MTX) is the first-line therapy for patients with rheumatoid arthritis (RA). However, approximately one quarter of patients discontinue MTX within 12 months. MTX failure, defined as MTX cessation or the addition of another anti-rheumatic drug, is usually due adverse event(s) and/or inefficacy. The aims of this study were to evaluate the rate and predictors of oral MTX failure. METHODS: Subjects were recruited from the Norfolk Arthritis Register (NOAR), a primary care-based inception cohort of patients with early inflammatory polyarthritis (IP)...
March 20, 2018: Arthritis Research & Therapy
Beatrice Bergström, Hans Carlsten, Anna-Karin Hultgård Ekwall
BACKGROUND: A key feature of joints in rheumatoid arthritis (RA) is the formation of hyperplastic destructive pannus tissue, which is orchestrated by activated fibroblast-like synoviocytes (FLS). We have demonstrated that the RA risk gene and tumor suppressor Limb bud and heart development (LBH) regulates cell cycle progression in FLS. Methotrexate (MTX) is the first-line treatment for RA, but its mechanisms of action remain incompletely understood. Here, we studied the effects of MTX on mitogen-induced FLS proliferation and expression of cell cycle regulators in vitro...
March 20, 2018: Arthritis Research & Therapy
Vu Huy Luong, Takenao Chino, Noritaka Oyama, Takashi Matsushita, Yoko Sasaki, Dai Ogura, Shin-Ichiro Niwa, Tanima Biswas, Akiyuki Hamasaki, Mikako Fujita, Yoshinari Okamoto, Masami Otsuka, Hironobu Ihn, Minoru Hasegawa
BACKGROUND: Transforming growth factor-β (TGF-β)/Smad signaling is well known to play a critical role in the pathogenesis of systemic sclerosis (SSc). We previously developed an artificial molecule, the histidine-pyridine-histidine ligand derivative HPH-15, which may have an antifibrotic effect. The purpose of the present study was to clarify the effects of this drug in human skin fibroblasts and in a preclinical model of SSc. METHODS: The effects of HPH-15 on expression of extracellular matrix components and TGF-β signaling in human dermal fibroblasts were analyzed...
March 15, 2018: Arthritis Research & Therapy
Monika Löfgren, Christina H Opava, Ingrid Demmelmaier, Cecilia Fridén, Ingrid E Lundberg, Birgitta Nordgren, Eva Kosek
BACKGROUND: We aimed to explore pressure pain sensitivity and the function of segmental and plurisegmental exercise-induced hypoalgesia (EIH) in persons with rheumatoid arthritis (RA) compared with healthy control subjects (HC). METHODS: Forty-six participants with RA (43 female, 3 male) and 20 HC (16 female, 4 male) participated in the study. Pressure pain thresholds, suprathreshold pressure pain at rest, and segmental and plurisegmental EIH during standardised submaximal contractions were assessed by algometry...
March 15, 2018: Arthritis Research & Therapy
Peter Nash, Philip J Mease, Iain B McInnes, Proton Rahman, Christopher T Ritchlin, Ricardo Blanco, Eva Dokoupilova, Mats Andersson, Radhika Kajekar, Shephard Mpofu, Luminita Pricop
BACKGROUND: The study aimed to assess 52-week efficacy and safety of secukinumab self-administration by autoinjector in patients with active psoriatic arthritis (PsA) in the FUTURE 3 study ( NCT01989468). METHODS: Patients (≥ 18 years of age; N = 414) with active PsA were randomized 1:1:1 to subcutaneous (s.c.) secukinumab 300 mg, 150 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and every 4 weeks thereafter. Per clinical response, placebo-treated patients were re-randomized to s...
March 15, 2018: Arthritis Research & Therapy
Quan-Bo Zhang, Yu-Feng Qing, Cong-Cong Yin, Li Zhou, Xian-Shuang Liu, Qing-Sheng Mi, Jing-Guo Zhou
BACKGROUND: MicroRNAs (miRNAs) serve as important regulators of inflammatory and immune responses and are implicated in several immune disorders including gouty arthritis. The expression of miR-146a is upregulated in the peripheral blood mononuclear cells of patients with inter-critical gout when compared to normouricemic and hyperuricemic controls and those patients with acute gout flares. However, the role of miR-146a in the development of gout remains unknown. Here, we used miR-146a knockout (KO) mice to test miR-146a function in a monosodium urate (MSU)-induced gouty arthritis model...
March 15, 2018: Arthritis Research & Therapy
Christian Schwedler, Thomas Häupl, Ulrich Kalus, Véronique Blanchard, Gerd-Rüdiger Burmester, Denis Poddubnyy, Berthold Hoppe
BACKGROUND: Galactosylation of immunoglobulin G (IgG) is reduced in rheumatoid arthritis (RA) and assumed to correlate with inflammation and altered humoral immunity. IgG hypogalactosylation also increases with age. To investigate dependencies in more detail, we compared IgG hypogalactosylation between patients with RA, patients with axial spondyloarthritis (axSpA), and healthy control subjects (HC), and we studied it in RA on the background of HLA-DRB1 shared epitope (SE), anticitrullinated protein antibodies (ACPA), and/or rheumatoid factor (RF) status...
March 14, 2018: Arthritis Research & Therapy
Kai Wang, Dongmei Zhang, Yan Liu, Xuan Wang, Jiantong Zhao, Tingting Sun, Tingting Jin, Baoli Li, Janak L Pathak
BACKGROUND: Traditional Chinese medicine (TCM) formula Bi-Qi capsule (Bi-Qi) is a commonly prescribed drug to treat rheumatoid arthritis (RA). However, the mechanism of Bi-Qi-mediated amelioration of RA pathogenesis is still a mystery. Collagen induced arthritis (CIA) in rats is an established model that shares many similarities with RA in humans. In this study we investigated the effect of Bi-Qi on the pathogenesis of CIA in rats. METHODS: CIA was developed in Sprague-Dawley (S...
March 14, 2018: Arthritis Research & Therapy
Tsutomu Takeuchi, Hisashi Yamanaka, Masayoshi Harigai, Ryo Tamamura, Yuichi Kato, Yoshifumi Ukyo, Toshikazu Nakano, Benjamin Hsu, Yoshiya Tanaka
BACKGROUND: Sirukumab, a high-affinity human monoclonal antibody that selectively binds to interleukin-6, has demonstrated efficacy in the treatment of rheumatoid arthritis (RA) in global phase 1 and phase 2 studies. The present study evaluated the safety and efficacy of sirukumab, as monotherapy in Japanese patients with RA refractory to methotrexate or sulfasalazine. METHODS: In this phase 3, double-blind study, 122 patients (age ≥ 20 years) were randomized (1:1, 61 patients in each arm) to sirukumab administered subcutaneously: 50 mg once every 4 weeks (q4w) or 100 mg once every 2 weeks (q2w) through 52 weeks...
March 7, 2018: Arthritis Research & Therapy
Yan Wen, Ping Li, Jingcan Hao, Chen Duan, Jing Han, Awen He, Yanan Du, Li Liu, Xiao Liang, Feng Zhang, Xiong Guo
BACKGROUND: Kashin-Beck disease (KBD) is an endemic osteochondropathy of unknown etiology. Osteoarthritis (OA) is a form of degenerative joint disease sharing similar clinical manifestations and pathological changes to articular cartilage with KBD. METHODS: A genome-wide DNA methylation profile of articular cartilage from five KBD patients and five OA patients was first performed using the Illumina Infinium HumanMethylation450 BeadChip. Together with a previous gene expression profiling dataset comparing KBD cartilage with OA cartilage, an integrative pathway enrichment analysis of the genome-wide DNA methylation and the mRNA expression profiles conducted in articular cartilage was performed by InCroMAP software...
March 7, 2018: Arthritis Research & Therapy
Janneke J de Winter, Marleen G van de Sande, Niklas Baerlecken, Inger Berg, Roberta Ramonda, Désirée van der Heijde, Floris A van Gaalen, Torsten Witte, Dominique L Baeten
BACKGROUND: Anti-CD74 IgG antibodies are reported to be elevated in patients with axial spondyloarthritis (axSpA). This study assessed the diagnostic value of anti-CD74 antibodies in patients with early axSpA. METHODS: Anti-CD74 IgG and IgA antibodies were first measured in an exploratory cohort of patients with radiographic axSpA (138 patients with ankylosing spondyloarthritis (AS)) and 57 healthy controls and then were measured in patients with early axSpA (n = 274) and with non-SpA chronic back pain (CBP) (n = 319), participating in the spondyloarthritis caught early (SPACE) prospective cohort study of patients under 45 years old with early back pain (for ≥ 3 months, but ≤ 2 years)...
March 1, 2018: Arthritis Research & Therapy
Jean-Pierre Pelletier, Jean-Pierre Raynauld, François Abram, Marc Dorais, Philippe Delorme, Johanne Martel-Pelletier
BACKGROUND: The weight of recommendation for intra-articular therapies such as hyaluronic acid injections varies from one set of guidelines to another, and they have not yet reached unanimity with respect to the usefulness of intra-articular hyaluronic acid (IAHA) injections for the symptomatic treatment of knee osteoarthritis (OA). Among the reasons for the controversy is that the current literature provides inconsistent results and conclusions about such treatment. This study aimed at identifying determinants associated with a better response to IAHA treatment in knee OA...
March 1, 2018: Arthritis Research & Therapy
Gianfranco Caselli, Albino Bonazzi, Marco Lanza, Flora Ferrari, Daniele Maggioni, Cristian Ferioli, Roberto Giambelli, Eleonora Comi, Silvia Zerbi, Marco Perrella, Ornella Letari, Elena Di Luccio, Milena Colovic, Stefano Persiani, Tiziano Zanelli, Laura Mennuni, Tiziana Piepoli, Lucio Claudio Rovati
BACKGROUND: Prostaglandin E2 (PGE2 ) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play a key role in the onset and progression of rheumatoid arthritis (RA). We present the pharmacological characterisation of CR6086, a novel EP4 receptor antagonist, and provide evidence for its potential as a disease-modifying anti-rheumatic drug (DMARD). METHODS: CR6086 affinity and pharmacodynamics were studied in EP4-expressing HEK293 cells by radioligand binding and cyclic adenosine monophosphate (cAMP) production, respectively...
March 1, 2018: Arthritis Research & Therapy
Tanya L Hoskin, Mary O Whipple, Sanjeev Nanda, Ann Vincent
BACKGROUND: Using self-report questionnaires of key fibromyalgia symptom domains (pain, fatigue, sleep disturbance, function, stiffness, dyscognition, depression, and anxiety), we previously identified four unique symptom clusters. The purpose of this study was to examine the stability of fibromyalgia symptom clusters between baseline and 2-year follow-up. METHODS: Women with a diagnosis of fibromyalgia completed the Brief Pain Inventory, Profile of Mood States, Medical Outcomes Study Sleep measure, Multidimensional Fatigue Inventory, Multiple Ability Self-Report Questionnaire, Revised Fibromyalgia Impact Questionnaire, and the 36-Item Short Form Survey Instrument at baseline...
February 27, 2018: Arthritis Research & Therapy
Janine S Hähnlein, Reza Nadafi, Tineke de Jong, Tamara H Ramwadhdoebe, Johanna F Semmelink, Karen I Maijer, IJsbrand A Zijlstra, Mario Maas, Danielle M Gerlag, Teunis B H Geijtenbeek, Paul P Tak, Reina E Mebius, Lisa G M van Baarsen
BACKGROUND: Systemic autoimmunity can be present years before clinical onset of rheumatoid arthritis (RA). Adaptive immunity is initiated in lymphoid tissue where lymph node stromal cells (LNSCs) regulate immune responses through their intimate connection with leucocytes. We postulate that malfunctioning of LNSCs creates a microenvironment in which normal immune responses are not properly controlled, possibly leading to autoimmune disease. In this study we established an experimental model for studying the functional capacities of human LNSCs during RA development...
February 26, 2018: Arthritis Research & Therapy
Emma C de Moel, Veerle F A M Derksen, Gerrie Stoeken, Leendert A Trouw, Holger Bang, Robbert J Goekoop, Irene Speyer, Tom W J Huizinga, Cornelia F Allaart, René E M Toes, Diane van der Woude
BACKGROUND: The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. It is yet unknown whether this varying breadth of the autoantibody profile is associated with treatment outcomes. Therefore, we investigated whether the composition of the autoantibody profile in RA, as a marker of the underlying immunopathology, influences initial and long-term treatment outcomes. METHODS: In serum from 399 seropositive patients with RA in the IMPROVED study, drawn at baseline and at the moment of drug tapering, we measured IgG, IgM, and IgA isotypes for anti-cyclic citrullinated peptide-2 and anti-carbamylated protein antibodies, IgM and IgA rheumatoid factor, and reactivity against four citrullinated and two acetylated peptides (anti-modified protein antibodies (AMPAs))...
February 26, 2018: Arthritis Research & Therapy
Teng Ma, Xiao Liu, Zhifu Cen, Chuan Xin, Mingfeng Guo, Chaoyu Zou, Wenpeng Song, Rou Xie, Kailun Wang, Hong Zhou, Jun Zhang, Zhen Wang, Ce Bian, Kaijun Cui, Jiong Li, Yu-Quan Wei, Jing Li, Xikun Zhou
BACKGROUND: Interleukin-1β (IL-1β) is a pivotal proinflammatory cytokine that is strongly associated with the inflammation of gout. However, the underlying mechanism through which the production of IL-1β is regulated has not been fully elucidated. Our previous work identified that miR-302b had an important immune regulatory role in bacterial lung infections. This study was conducted to evaluate the function of miR-302b on monosodium urate (MSU) crystal-induced inflammation and its mechanism...
February 26, 2018: Arthritis Research & Therapy
Uta Hardt, Anders Larsson, Iva Gunnarsson, Robert M Clancy, Michelle Petri, Jill P Buyon, Gregg J Silverman, Elisabet Svenungsson, Caroline Grönwall
BACKGROUND: Immunoglobulin M (IgM) autoreactivity to malondialdehyde (MDA) protein modifications is part of the natural antibody repertoire in health and may have beneficial functions. In contrast, IgG anti-MDA are increased in chronic inflammation and autoimmunity and may instead have pathogenic properties. METHODS: Herein, we investigated serum IgG anti-MDA levels by enzyme-linked immunosorbent assay (ELISA) in 398 systemic lupus erythematosus (SLE) patients in the Swedish Karolinska SLE cohort and compared these to findings in 225 US SLE patients from New York University and Johns Hopkins University...
February 26, 2018: Arthritis Research & Therapy
Anh Hoang, Susan M Goodman, Iris Y Navarro-Millán, Lisa A Mandl, Mark P Figgie, Mathias P Bostrom, Douglas E Padgett, Peter K Sculco, Alexander S McLawhorn, Jasvinder A Singh
Unfortunately, after publication of this article [1], it was noticed that Table 2 was not correctly formatted during the production process. The corrected Table 2 can be seen below and the original article has been updated to match.
February 14, 2018: Arthritis Research & Therapy
Deborah R Winter
High-throughput sequencing assays have become an increasingly common part of biological research across multiple fields. Even as the resulting sequences pile up in public databases, it is not always obvious how to make use of these data sets. Functional genomics offers approaches to integrate these "big" data into our understanding of rheumatic diseases. This review aims to provide a primer on thinking about big data from functional genomics in the context of rheumatology, using examples from the field's literature as well as the author's own work to illustrate the execution of functional genomics research...
February 12, 2018: Arthritis Research & Therapy
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