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Arthritis & Rheumatology

Jyun-Pei Jhou, I-Shing Yu, Haw Hwai, Chih-Shan Chen, Pei-Lung Chen, Shiang-Jong Tzeng
OBJECTIVE: FcγRIIB is an essential negative regulator of B cells to block BCR signaling and to trigger c-Abl-dependent apoptosis of B cells. FcγRIIB-deficient mice display splenomegaly with expansion of B cells, leading to lupus. FcγRIIB-I232T is a hypo-functional polymorphism associated with lupus susceptibility in humans, an autoimmune disease linked to diminished deletion of autoreactive B cells. In the context of FcγRIIB-I232T polymorphism, we investigated the role of FcγRIIB in the deletion of low-affinity germinal center (GC) B cells, an important mechanism for preventing autoimmunity...
May 17, 2018: Arthritis & Rheumatology
Évelyne Vinet, Cristiano De Moura, Christian A Pineau, Michal Abrahamowicz, Jeffrey R Curtis, Sasha Bernatsky
OBJECTIVE: To evaluate the risk of serious infections in rheumatoid arthritis (RA) offspring exposed to tumour necrosis factor α inhibitors (TNFi) in the gestational period compared to unexposed RA offspring, as well as to children from the general population. METHODS: We used US claim data (2011-2015) to identify 2 989 RA offspring and a randomly selected group of 14 596 control children, matched ≥4:1 for maternal age, year of delivery, and state of residence...
May 17, 2018: Arthritis & Rheumatology
Harry Karmouty-Quintana, Jose G Molina, Kemly Philip, Chiara Bellocchi, Brent Gudenkauf, Minghua Wu, Ning-Yuan Chen, Scott D Collum, Junsuk Ko, Sandeep K Agarwal, Shervin Assassi, Hongyan Zhong, Michael R Blackburn, Tingting Weng
OBJECTIVE: Systemic sclerosis (SSc - scleroderma) is a chronic disease that affects the skin and various internal organs. Dermal fibrosis is a major component of this disease. The mechanisms that promote dermal fibrosis remain elusive. Elevations in tissue adenosine levels and the subsequent engagement of the pro-fibrotic A2B adenosine receptor (ADORA2B) have been shown to regulate fibrosis in multiple organs including the lung, kidney and penis; however, the role of the ADORA2B in dermal fibrosis has not been investigated...
May 17, 2018: Arthritis & Rheumatology
Yvonne C Lee, Vitaly Napadow, Marco L Loggia
No abstract text is available yet for this article.
May 15, 2018: Arthritis & Rheumatology
Jian-Lu Wei, Wenyu Fu, Aubryanna Hettinghouse, Wen-Jun He, Kenneth E Lipson, Chuan-Ju Liu
OBJECTIVE: It has been reported that a disintegrin and metalloproteinase with thrombospondin motifs-12 (ADAMTS-12) is a susceptibility gene for rheumatoid arthritis (RA) development, and its level is significantly increased in RA patients. In addition, ADAMTS-12 was also reported to be required for normal inflammation. This study aims to determine the role of ADAMTS-12 and the underlying mechanisms in the pathogenesis of inflammatory arthritis. METHODS: The collagen-induced arthritis (CIA) model was established in ADAMTS-12-deficient mice and their control littermates to determine the role of ADAMTS-12 in vivo; microCT scanning was used to demonstrate the destruction of ankle joint; histological analysis illustrated synovitis, pannus formation, as well as bone and cartilage destruction; ELISA was performed to measure serum levels of inflammatory cytokines; Protein-protein interaction assays were performed to detect the interactions of ADAMTS-12 and its various deletion mutants with connective tissue growth factor (CTGF)...
May 11, 2018: Arthritis & Rheumatology
Julius Birnbaum, Ahmet Hoke, Aliya Lalji, Peter Calabresi, Pavan Bhargava, Livia Casciola-Rosen
OBJECTIVE: Autoantibodies are clinically useful for phenotyping patients across the spectrum of autoimmune rheumatic diseases. Using serum from a patient with Sjögren's Syndrome (SS), we detected a new specificity by immunoblotting. The purpose of this study was to identify this autoantibody and to evaluate its disease specificity. METHODS: A prominent 40 kDa band was detected when immunoblots were performed using a SS patient serum and lysate from rat dorsal root ganglia (DRG)...
May 11, 2018: Arthritis & Rheumatology
An Tran-Duy, Marjan Ghiti Moghadam, Martijn A H Oude Voshaar, Harald E Vonkeman, Annelies Boonen, Philip Clarke, Geoff McColl, Peter M Ten Klooster, T R Zijlstra, Willem F Lems, N Riyazi, E N Griep, J M W Hazes, Robert Landewé, Hein J Bernelot Moens, Piet L C M van Riel, Mart A F J van de Laar, T L Jansen
OBJECTIVE: To evaluate, from a societal perspective, the incremental cost-effectiveness of withdrawing tumor necrosis factor inhibitors (TNFis) compared to continuation of these drugs within a one-year randomized trial among patients with rheumatoid arthritis (RA) having longstanding stable disease activity or remission. METHODS: Data were collected from a pragmatic, open label trial. Cost-utility analysis was performed using the non-parametric bootstrapping method and a cost-effectiveness acceptability curve was constructed using the net-monetary benefit (NMB) framework, where a willingness-to-accept threshold (WTA) was defined as the minimal cost saved that a patient accepted for each quality-adjusted life year (QALY) lost...
May 9, 2018: Arthritis & Rheumatology
Gaëlle Varkas, Nathan Vastesaeger, Heleen Cypers, Roos Colman, Thomas Renson, Liesbet Van Praet, Philippe Carron, F Raeman, Mieke Devinck, Lieve Gyselbrecht, Luc Corluy, Yves Piette, Jan Lenaerts, Kristof Thevissen, Benedicte Vanneuville, Filip Van den Bosch, Dirk Elewaut
OBJECTIVE: To determine the link between extra-articular manifestations (EAMs) and baseline patient characteristics, and to define their potentially differential prognostic value in two large nation-wide and independent AxSpA cohorts with distinct recruitment periods. METHODS: The analyzed data originate from the (Be-)Giant cohort which includes consecutive patients with AxSpA since 2010, whereas ASPECT which includes information on consecutive patients with ankylosing spondylitis (AS) and probable AS between February 2004 and 2005...
May 9, 2018: Arthritis & Rheumatology
Markus Bredemeier
We read with interest the study by Coburn et al. (1), a methodologically sound propensity-score matched cohort study evaluating the effect of dose escalation of allopurinol on cardiovascular (CV) and overall mortality. The results indicate that increasing doses carry a higher risk of mortality, but the authors comment that failure in achieving doses up to 600 mg may have contributed to the absence of protective effect. This article is protected by copyright. All rights reserved.
May 9, 2018: Arthritis & Rheumatology
Brian W Coburn, Kaleb Michaud, Debra A Bergman, Ted R Mikuls
We thank Dr. Bredemeier for his comments regarding our manuscript on allopurinol dose escalation and mortality. He raises important evidence to consider in support of an interesting hypothesis that dose escalation may be unnecessary for allopurinol's cardiovascular (CV) protection and may actually be related to adverse CV outcomes. While we agree that evidence exists suggesting that low doses of allopurinol may be sufficient for CV protection, we believe that the studies cited highlight a number of areas where knowledge gaps remain which preclude any definitive conclusions about the effect of dose escalation...
May 8, 2018: Arthritis & Rheumatology
Cristina Redondo, Ana Martínez-Feito, Chamaida Plasencia-Rodríguez, Victoria Navarro-Compán, Laura Nuño-Nuño, Diana Peiteado, Alejandro Villalba, Andrea Jochems, Dora Pascual-Salcedo, Alejandro Balsa
Golimumab (GLM) is a tumor necrosis factor inhibitor (TNFi) used as Spondyloarthritis (SpA) treatment(1) . There is increasing evidence of the feasibility of using TNFi levels as a guide for clinicians to an optimized strategy(2-4) . Up to now, a few studies have investigated the predictive value of GLM-levels in the clinical response of several inflammatory diseases(5-8) , but none concerning GLM reduction therapy in SpA based on drug-levels measurement is available. This article is protected by copyright...
May 7, 2018: Arthritis & Rheumatology
Janet E Pope
Nearly half of all pregnancies are not planned so inadvertent drug exposure is a reality in women with chronic inflammatory diseases (1). Patients taking medications for their rheumatic diseases during pregnancy, and their physicians may perceive the stakes to be high. There are two patients to consider. We need to accurately advise our pregnant patients with the most updated information weighing trade-offs of disease flares from stopping medications where disease activity can result in prematurity vs. potential drug effects which can also be associated with negative pregnancy outcomes This article is protected by copyright...
May 7, 2018: Arthritis & Rheumatology
Yannick Allanore, Oliver Distler, Alexandre Jagerschmidt, Stephane Illiano, Laetitia Ledein, Eric Boitier, Inoncent Agueusop, Christopher P Denton, Dinesh Khanna
BACKGROUND: Preclinical studies suggest a role for lysophosphatidic acid (LPA) in the pathogenesis of systemic sclerosis (SSc). OBJECTIVES: SAR100842, a potent selective oral antagonist of LPA1 receptor, was assessed for safety, biomarkers and clinical efficacy in patients with diffuse cutaneous SSc (dcSSc). METHODS: An 8-week double-blind, randomized, placebo-controlled study followed by a 16-week open label extension with SAR100842 was performed in patients with early dcSSc and a baseline Rodnan skin score (mRSS) of at least 15...
May 6, 2018: Arthritis & Rheumatology
Colin Shepherd, Dongxing Zhu, Andrew J Skelton, Jennifer Combe, Harrison Threadgold, Linyi Zhu, Tonia L Vincent, Paul Stuart, Louise N Reynard, John Loughlin
OBJECTIVE: To identify the functional single nucleotide polymorphisms (SNPs) and mechanisms conferring increased hand osteoarthritis (OA) risk at the ALDH1A2 locus, which is a retinoic acid (RA) regulatory gene. METHODS: Tissues from 247 knee, hip or hand OA patients who had undergone joint surgery were included. RNA-sequencing was used to investigate differential expression of ALDH1A2 and other RA signalling pathway genes in cartilage. ALDH1A2 expression in multiple joint tissues was quantified by qPCR...
May 6, 2018: Arthritis & Rheumatology
Pravitt Gourh, Elaine F Remmers, Steven E Boyden, Theresa Alexander, Nadia D Morgan, Ami A Shah, Maureen D Mayes, Ayo Doumatey, Amy R Bentley, Daniel Shriner, Robyn T Domsic, Thomas A Medsger, Virginia D Steen, Paula S Ramos, Richard M Silver, Benjamin Korman, John Varga, Elena Schiopu, Dinesh Khanna, Vivien Hsu, Jessica K Gordon, Lesley Ann Saketkoo, Heather Gladue, Brynn Kron, Lindsey A Criswell, Chris T Derk, S Louis Bridges, Victoria K Shanmugam, Kathleen D Kolstad, Lorinda Chung, Reem Jan, Elana J Bernstein, Avram Goldberg, Marcin Trojanowski, Suzanne Kafaja, Kathleen M Maksimowicz-McKinnon, James C Mullikin, Adebowale Adeyemo, Charles Rotimi, Francesco Boin, Daniel L Kastner, Fredrick M Wigley
OBJECTIVE: Whole-exome sequencing (WES) studies in systemic sclerosis (SSc) patients of European American (EA) ancestry have identified variants in the ATP8B4 gene and enrichment of variants in genes in the extracellular matrix (ECM)-related pathway increasing SSc susceptibility. Our goal was to evaluate the association of the ATP8B4 gene and the ECM-related pathway with SSc in a cohort of African Americans (AA). METHODS: SSc patients of AA ancestry were enrolled from 23 academic centers across the United States under the Genome Research in African American Scleroderma Patients (GRASP) consortium...
May 6, 2018: Arthritis & Rheumatology
Christoph Tappeiner, Jens Klotsche, Claudia Sengler, Martina Niewerth, Ina Liedmann, Karoline Walscheid, Miha Lavric, Dirk Foell, Kirsten Minden, Arnd Heiligenhaus
PURPOSE: To analyze the prognostic value of demographic, clinical, and therapeutic factors and laboratory biomarkers, and to assess their role in predicting uveitis occurrence in patients with JIA. METHODS: Patients with JIA were enrolled within the first year after JIA diagnosis. Demographic and clinical parameters were documented. Serum samples were collected at study enrollment, at 3-month follow-up visits within the first year, and then 6-monthly. A multivariable Cox regression analysis was performed to evaluate the impact of demographic, clinical, laboratory, and therapeutic parameters on uveitis onset...
May 6, 2018: Arthritis & Rheumatology
Philippe Mertz, Mathilde Herber, Juliette Jeannel, Anne-Sophie Korganow, Aurélien Guffroy
A 69-year-old woman with asthenia, anorexia and weight loss lasting for several weeks was referred for a subacute onset of painful permanent acrocyanosis of the four extremities without Raynaud's phenomenon. She also had concomitantly developed grade I/IV (NYHA) dyspnea. A physical examination revealed livedoid acrocyanosis of distal phalanges of the hands (Fig. 1A), which was associated with flame-shaped hemorrhages (Fig. 1B, arrow-head), dilated capillaries at the proximal nailfolds (Fig. 1B, arrow), Gottron's sign over the MCP and PIP joints and a discrete heliotrope rash with a palpable V-shaped rash of the upper chest and forehead...
May 6, 2018: Arthritis & Rheumatology
Chan Kim, Michael Nevitt, Ali Guermazi, Jingbo Niu, Margaret Clancy, Irina Tolstykh, Pia M Jungmann, Nancy E Lane, Neil A Segal, Wiiliam F Harvey, Cora E Lewis, David T Felson
OBJECTIVE: Studies suggest that persons with a 2 cm shorter limb have an increased risk of knee osteoarthritis (OA) in that limb. We examined whether leg length inequality (LLI) confers an increased risk of hip OA. METHODS: Using long limb radiographs from MOST and the Osteoarthritis Initiative, we measured LLI and scored hip radiographs which were obtained at baseline and 3-5 year follow-up. We examined the association of >1 cm LLI and >2 cm of LLI with radiographic hip OA cross-sectionally and longitudinally, assessing risk in shorter limbs and longer limbs compared with limbs with no LLI...
April 26, 2018: Arthritis & Rheumatology
Jing J Wang, Joanne H Reed, Alex D Colella, Amanda J Russell, William Murray-Brown, Tim K Chataway, Katherine J L Jackson, Christopher C Goodnow, Tom P Gordon
OBJECTIVE: Rheumatoid factors (RFs) are associated with systemic disease in primary Sjögren's syndrome (SS) and may be pathogenic as mixed cryoglobulins. Current detection methods cannot resolve RFs at a molecular level. Here, we perform the first proteomic and transcriptomic analysis of secreted and membrane-bound RF IgM in primary SS and identify unique heavy (H)-chain peptide signatures for RF clonotype tracking. METHODS: Purified H-chains of serum RFs (IgH-RF) from 15 primary SS patients were subjected to de novo mass spectrometric sequencing...
April 26, 2018: Arthritis & Rheumatology
Sung Kweon Cho, Yoosoo Chang, Inah Kim, Seungho Ryu
OBJECTIVE: In addition to the controversy regarding the association between hyperuricemia and cardiovascular disease (CVD) mortality, few studies have examined the impact of low uric acid level on mortality. The present study evaluated the relationship of both low and high uric acid level with the risk of all-cause and cause-specific mortality in a large sample of Korean adults over a full range of uric acid levels. METHODS: A cohort study was performed for 375,163 South Korean men and women who underwent a health checkup from 2002 to 2012...
April 25, 2018: Arthritis & Rheumatology
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