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Arthritis & Rheumatology

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https://www.readbyqxmd.com/read/29342508/features-treatment-and-outcomes-of-macrophage-activation-syndrome-in-childhood-onset-systemic-lupus-erythematosus
#1
R Ezequiel Borgia, Maya Gerstein, Deborah M Levy, Earl D Silverman, Linda T Hiraki
OBJECTIVE: To describe the features and treatment of macrophage activation syndrome (MAS) in a childhood-onset systemic lupus erythematosus (cSLE) single centre cohort, and compare the cSLE manifestations and outcomes between those with and without MAS. METHODS: We included all cSLE patients followed at SickKids Hospital from 2002-12, and identified those also diagnosed with MAS. Demographic, clinical and laboratory features of MAS and SLE, medication use, hospital and PICU admissions as well as damage indices and mortality were extracted from the Lupus database...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29342507/the-role-of-autophagy-in-the-degradation-of-misfolded-hla-b27-heavy-chains
#2
Fatemeh Navid, Gerlinde Layh-Schmitt, Keith A Sikora, Antony Cougnoux, Robert A Colbert
OBJECTIVE: To determine whether autophagy is involved in the degradation of misfolded HLA-B27 in experimental spondyloarthritis. METHODS: Bone marrow derived macrophages from HLA-B27 and human β2 m (hβ2 m) transgenic rats were examined with and without IFNγ and proteasome or autophagy inhibitors. Immunoprecipitation, western blotting, and immunofluorescence were used to measure HLA-B27 heavy chains and autophagy. Autophagy was induced using rapamycin. HLA-B7/hβ2 m transgenic and wild type rat macrophages were used as controls...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29342505/reply-to-does-rheumatoid-arthritis-cause-an-obesity-paradox
#3
Jeffrey A Sparks, Elizabeth W Karlson
We are grateful to Dr. Baker and colleagues for their interest in our recent work and agree with their interpretation of our study that investigated weight change in the early rheumatoid arthritis (RA) period among women diagnosed with RA and matched comparators. As they point out, any weight loss and severe weight loss in the early RA or matched index period were both more common among those with RA than matched comparators. The authors suggest that this increased frequency of weight loss may exacerbate the obesity paradox for mortality among patients with RA...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29342503/the-molecular-basis-for-dysregulated-activation-of-nkx2-5-in-vascular-remodelling-of-systemic-sclerosis
#4
Athina Dritsoula, Ioannis Papaioannou, Sandra G Guerra, Carmen Fonseca, Javier Martin, Ariane L Herrick, David J Abraham, Christopher P Denton, Markella Ponticos
OBJECTIVE: NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling. In this study, we sought to investigate mechanisms that activate NKX2-5 expression in diseased vessels, such as scleroderma associated pulmonary hypertension (SSc-PH), and identify genetic variability that potentially underlies susceptibility to specific vascular complications...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29342502/antiphospholipid-antibodies-inhibit-trophoblast-toll-like-receptor-and-inflammasome-negative-regulators
#5
Melissa J Mulla, Ingrid C Weel, Julie A Potter, Stefan M Gysler, Jane E Salmon, Maria T S Peraçoli, Carla V Rothlin, Lawrence W Chamley, Vikki M Abrahams
OBJECTIVE: Women with antiphospholipid antibodies (aPL) are at risk for pregnancy complications associated with poor placentation and placental inflammation. While these antibodies are heterogeneous, some anti-β2 GPI antibodies can activate human first trimester trophoblast TLR4 and NLRP3. The objective of this study was to determine the role of negative regulators of TLR and inflammasome function in aPL-induced trophoblast inflammation. METHODS: Human trophoblast cells were treated with or without anti-β2 GPI aPL or control IgG in the presence or absence of the common TAM receptor ligand, GAS6, or the autophagy inducer, rapamycin...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29342501/selective-activation-of-tumor-necrosis-factor-receptor-2-induces-anti-inflammatory-responses-and-alleviates-experimental-arthritis
#6
Roman Fischer, Marcel Proske, Maëlle Duffey, Hubert Stangl, George F Martinez, Nathalie Peters, Alexandra Kraske, Rainer H Straub, John R Bethea, Roland E Kontermann, Klaus Pfizenmaier
OBJECTIVES: Regulatory T cells (Tregs) modulate immune responses and can suppress the development of autoimmune diseases. Tumor necrosis factor receptor 2 (TNFR2) has been recognized as a key receptor on these cells that facilitates expansion and stabilization of CD4+ Tregs. Here, we investigated the therapeutic activity of a novel TNFR2 agonist in experimental arthritis and the role of different Treg subsets. METHODS: A novel mouse TNFR2-selective fusion protein (EHD2-sc-mTNFR2 ) was generated by genetic engineering...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29342500/does-rheumatoid-arthritis-cause-an-obesity-paradox-comment-on-the-study-by-sparks-et%C3%A2-al
#7
LETTER
Joshua F Baker, Gail Kerr, Ted R Mikuls
We read with interest the article by Sparks et al. evaluating the association between weight changes in the peri-diagnosis period with mortality among patients with rheumatoid arthritis (1). In this study, the investigators clearly show that weight loss is an important predictor of early mortality both in RA and non-RA patients. Indeed, and perhaps not surprisingly, unintentional weight loss is likely to be a poor prognostic sign regardless of its cause. This article is protected by copyright. All rights reserved...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29342499/efficacy-and-safety-of-cyclophosphamide-treatment-in-severe-juvenile-dermatomyositis-shown-by-marginal-structural-modelling
#8
Claire T Deakin, Raquel Campanilho-Marques, Stefania Simou, Elena Moraitis, Lucy R Wedderburn, Eleanor Pullenayegum, Clarissa A Pilkington
OBJECTIVE: In patients with severe or refractory juvenile dermatomyositis (JDM), second-line treatments may be required. Cyclophosphamide (CYC) is used to treat some connective tissue diseases, but evidence of efficacy in JDM is limited. This study aimed to describe clinical improvement in JDM patients treated with CYC and model efficacy of CYC compared to patients not treated with CYC. METHODS: Clinical data on skin, global and muscle disease were analyzed from patients recruited to the Juvenile Dermatomyositis Cohort and Biomarker Study...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29333701/the-childhood-arthritis-rheumatology-research-alliance-consensus-treatment-plans-towards-comparative-effectiveness-in-the-pediatric-rheumatic-diseases
#9
REVIEW
Sarah Ringold, Peter A Nigrovic, Brian M Feldman, George A Tomlinson, Emily von Scheven, Carol A Wallace, Adam M Huber, Laura E Schanberg, Suzanne C Li, Pamela F Weiss, Robert C Fuhlbrigge, Esi M Morgan, Yukiko Kimura
The pediatric rheumatic diseases are a heterogeneous group of rare diseases, posing a number of challenges for the use of traditional clinical and translational research approaches. Innovative comparative effectiveness approaches are needed to efficiently study treatment approaches and disease outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed the consensus treatment plan (CTP) approach as a comparative effectiveness tool for research in pediatric rheumatology. CTPs are treatment strategies, developed by consensus methods among CARRA members, intended to reduce variation in treatment approaches, standardize outcome measurements, and allow for comparison of the effectiveness of different approaches with the goal of improving disease outcomes...
January 15, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29316374/switched-memory-b-cells-are-increased-in-oligoarticular-and-polyarticular-juvenile-idiopathic-arthritis-and-their-change-over-time-is-related-to-response-to-tnf-inhibitors
#10
Emiliano Marasco, Angela Aquilani, Simona Cascioli, Gian Marco Moneta, Ivan Caiello, Chiara Farroni, Ezio Giorda, Valentina D'Oria, Denise Pires Marafon, Silvia Magni-Manzoni, Rita Carsetti, Fabrizio De Benedetti
OBJECTIVES: To investigate if abnormalities in B-cell subsets in JIA patients correlated with clinical features and response to treatment. METHODS: 109 patients diagnosed with oligo-JIA or poly-JIA were enrolled in the study. B-cell subsets in peripheral blood and synovial fluid were analyzed by flow cytometry. RESULTS: Switched memory B-cells (SwM B-cells) were significantly (p<0.0001) increased in patients compared to age- matched healthy controls (HC)...
January 5, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29316369/x-chromosome-short-arm-involvement-in-autoimmune-diseases-comment-on-the-report-by-sharma-et-al
#11
LETTER
Wesley Brooks
Sharma, et al. reported associations of X chromosome abnormalities with systemic lupus erythematosus (SLE) and Sjogren's syndrome (SjS).1 They proposed that genes located on the X chromosome short arm (Xp) mediate the sex bias of SLE and/or SjS. We had been thinking along these lines too and would like to add that, in X-linked chronic granulomatous disease (X-CGD) in which chromatin is duplicated from Xp21.2 to the Xp terminus, some of the mothers, who are X-CGD carriers, exhibit lupus-like symptoms.2 This article is protected by copyright...
January 5, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29316339/reply-x-chromosome-short-arm-involvement-in-autoimmune-diseases-comment-on-the-report-by-sharma-et-al
#12
R Hal Scofield, Rohan Sharma, Valerie M Harris
Studying Klinefelter's syndrome (male 47,XXY) and triple X (female 4,7XXX), we propose that the number of X chromosomes mediates the female bias of systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). Our recent paper described SLE and SS patients with extremely rare X chromosome aneuploides in which distal Xp was triplicated, implicating genes lying on the short arm of X1 . Brooks points out that X-linked chronic granulomatosus disease (X-CGD) can also have gene duplication from Xp21.2 to Xp terminus, and some female carriers of X-CDG have a cutaneous lupus-like illness...
January 5, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29287312/hip-and-knee-arthroplasty-utilization-and-outcomes-in-the-united-states-and-canada-an-analysis-of-new-york-and-ontario-administrative-data
#13
Peter Cram, Bruce E Landon, John Matelski, Vicki Ling, Therese A Stukel, J Michael Paterson, Rajiv Gandhi, Gillian A Hawker, Bheeshma Ravi
OBJECTIVE: Total knee and total hip arthroplasty (TKA and THA) are common and effective surgical procedures. We compared utilization and short-term outcomes of primary TKA and THA in adjacent regions of Canada and the United States. METHODS: Retrospective cohort study of patients who underwent primary TKA or THA using administrative data from New York (NY) and Ontario in 2012-2013. We compared TKA and THA patient demographics, per-capita utilization, and short-term outcomes between jurisdictions...
December 29, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29287311/hypomethylation-of-cyp2e1-and-dusp22-promoters-associated-with-disease-activity-and-erosive-disease-among-rheumatoid-arthritis-patients
#14
Amanda Mok, Brooke Rhead, Calliope Holingue, Xiaorong Shao, Hong L Quach, Diana Quach, Elizabeth Sinclair, Jonathan Graf, John Imboden, Thomas Link, Ruby Harrison, Vladimir Chernitskiy, Lisa F Barcellos, Lindsey A Criswell
OBJECTIVE: Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). This study aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with four clinical outcomes among RA patients. METHODS: Peripheral blood samples were taken from 63 patients in the University of California, San Francisco RA cohort (all satisfied ACR classification criteria; 57 were seropositive). Cells were FACS-sorted into four immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naïve T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips...
December 29, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29287308/chikungunya-virus-arthritis-implications-of-acute-and-chronic-inflammation-mechanisms-on-patient-management
#15
REVIEW
Ali Zaid, Patrick Gérardin, Adam Taylor, Helen Mostafavi, Denis Malvy, Suresh Mahalingam
In the past decade, arboviruses - arthropod-borne viruses - have been the focus of public health institutions worldwide following a spate of devastating outbreaks. Chikungunya virus (CHIKV), an arbovirus that belongs to the alphavirus genus, is a re-emerging arthritogenic virus that has caused explosive outbreaks since 2006, notably in the Reunion Island, and more recently in the Caribbean, South America, India and South-East Asia. The severity of arthritic disease caused by CHIKV has prompted public health authorities of affected countries to develop specific guidelines to tackle this pathogen...
December 29, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29287307/effects-of-hla-b27-on-gut-microbiota-in-experimental-spondyloarthritis-implicate-an-ecological-model-of-dysbiosis
#16
Tejpal Gill, Mark Asquith, Stephen R Brooks, James T Rosenbaum, Robert A Colbert
OBJECTIVES: We investigated whether HLA-B27-mediated experimental spondyloarthritis (SpA) is associated with a common gut microbial signature to identify potential drivers of pathogenesis. METHODS: Effects of HLA-B27 on three genetic backgrounds, Dark Agouti (DA), Lewis, and Fischer were compared, using wild-type littermates and HLA-B7 transgenic Lewis rats as controls. At 2, 3-4, and 6-8 months of age, cecal and colonic tissue or contents were analyzed by histology for inflammation, RNA-Seq for gene expression differences, and 16S rRNA gene sequencing for microbiota differences...
December 29, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29287304/the-tumor-like-phenotype-of-rheumatoid-synovium-molecular-profiling-and-prospects-for-precision-medicine
#17
REVIEW
Sungyong You, Jung Hee Koh, Lin Leng, Wan-Uk Kim, Richard Bucala
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by a destructive hyperplasia of synovium. Fibroblast-like synoviocytes (FLS) are a major component of synovial pannus and actively participate in the pathologic progression of RA. How rheumatoid FLS acquire and sustain such a uniquely aggressive phenotype remains poorly understood. We describe the current state of knowledge of the molecular alterations in rheumatoid FLS at the genomic, epigenomic, transcriptomic, proteomic, and metabolomic levels, which offers a comprehensive and complementary reconstruction of the potential pathways leading to rheumatoid pannus...
December 29, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29287303/high-levels-of-dek-autoantibodies-in-sera-of-polyarticular-jia-patients-and-in-early-flare-following-cessation-of-anti-tnf-therapy
#18
Nirit Mor-Vaknin, Miguel Rivas, Maureen Legendre, Smriti Mohan, Ye Yuanfan, Theresa Mau, Anne Johnson, Bin Huang, Lili Zhao, Yukiko Kimura, Steven J Spalding, Paula W Morris, Beth S Gottlieb, Karen Onel, Judyann C Olson, Barbara S Edelheit, Michael Shishov, Lawrence K Jung, Elaine A Cassidy, Sampath Prahalad, Murray H Passo, Timothy Beukelman, Jay Mehta, Edward H Giannini, Barbara S Adams, Daniel J Lovell, David M Markovitz
OBJECTIVE: The nuclear oncoprotein DEK is an autoantigen associated with juvenile idiopathic arthritis (JIA), especially the oligoarticular subtype. DEK is a secreted chemoatactic factor. Abundant DEK and DEK autoantibodies are found in the inflamed JIA synovium. In screening sera samples from two different JIA patient cohorts for DEK autoantibodies, we now further characterize the nature of DEK autoantibodies. METHODS: DEK autoantibody levels were analyzed in sera from 33 JIA patients, 13 patients with other inflammatory conditions, and 11 healthy controls and 89 sera samples from JIA patients undergoing anti-TNF therapy...
December 29, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29266879/differences-in-safety-of-non-steroidal-anti-inflammatory-drugs-in-patients-with-osteoarthritis-and-rheumatoid-arthritis-a-randomized-clinical-trial
#19
Daniel H Solomon, M Elaine Husni, Katherine E Wolski, Lisa M Wisniewski, Jeffrey S Borer, David Y Graham, Peter Libby, A Michael Lincoff, Thomas F Lüscher, Venu Menon, Neville D Yeomans, Qiuqing Wang, Weihang Bao, Manuela F Berger, Steven E Nissen
OBJECTIVE: To determine relative cardiovascular, gastrointestinal and renal safety of celecoxib, compared with ibuprofen and naproxen during chronic use in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: 24,081 patients with OA or RA at moderate or high cardiovascular risk enrolled internationally in a double-blind randomized controlled trial. Interventions included celecoxib 100-200mg bid, ibuprofen 600-800mg tid, or naproxen 375-500mg bid...
December 20, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29266856/a-cross-sectional-analysis-of-chikungunya-arthritis-patients-22-months-post-infection-demonstrate-no-detectable-viral-persistence-in-synovial-fluid
#20
Aileen Y Chang, Karen A O Martins, Liliana Encinales, St Patrick Reid, Marlon Acuña, Carlos Encinales, Christian B Matranga, Nelly Pacheco, Carlos Cure, Bhavarth Shukla, Teofilo Ruiz Arteta, Richard Amdur, Lisa H Cazares, Melissa Gregory, Michael D Ward, Alexandra Porras, Alejandro Rico Mendoza, Lian Dong, Tara Kenny, Ernie Brueggemann, Lydia G Downey, Priyanka Kamalapathy, Paola Lichtenberger, Orlando Falls, Gary L Simon, Jeffrey Bethony, Gary S Firestein
OBJECTIVE: Determine if chikungunya virus (CHIKV) persists in synovial fluid post-infection, potentially serving as a causative mechanism of persistent arthritis. METHODS: This is a cross-sectional study of 38 Colombian participants with clinical CHIKV infection during the 2014-2015 epidemic who reported chronic arthritis and ten location-matched CHIKV- and arthritis-negative controls. Prior CHIKV infection status was serologically confirmed and the presence of synovial fluid CHIKV, viral RNA, and viral proteins was measured by viral culture, quantitative reverse transcription PCR (qRT-PCR), and mass spectrometry...
December 20, 2017: Arthritis & Rheumatology
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