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Arthritis & Rheumatology

Carolyn J Kushner, Josef Symon S Concha, David R Pearson, Victoria P Werth
A 77-year old Caucasian woman presented with a 10-year history of discoid, scaly, pigmented, telangiectatic and atrophic patches on the upper cheeks (Figure 1), and gradually progressive alopecia of the frontal scalp (Figure 2). A biopsy of the cheek demonstrated interface dermatitis, epidermal hyperkeratosis and atrophy, dyskeratotic keratinocytes, and a superficial perivascular lymphohistiocytic infiltrate with pigment incontinence. She had a low-titer ANA (1:80, nucleolar), negative SS-A and SS-B, and unremarkable blood counts/chemistry...
November 14, 2018: Arthritis & Rheumatology
Ronald van Vollenhoven, Eun Bong Lee, Sander Strengholt, Christopher Mojcik, Hernan Valdez, Sriram Krishnaswami, Pinaki Biswas, Irina Lazariciu, Anasuya Hazra, James D Clark, Jennifer Hodge, Lisy Wang, Ernest Choy
OBJECTIVE: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Altered lymphocyte cell counts, and a potential association with increased infection rates, have been reported in patients with RA treated with JAK inhibitors. We evaluated the short-, mid-, and long-term effects of tofacitinib on lymphocytes and infection rates in patients with RA. METHODS: In this post-hoc analysis, absolute lymphocyte counts (ALCs) were obtained from Phase (P)3 (12-24 months) and P1/2/3/long-term extension (LTE) ('All RA' population; ≤117 months) studies of tofacitinib; lymphocyte subset counts (LSCs) were from P2 studies (1...
November 14, 2018: Arthritis & Rheumatology
Seerapani Gopaluni, Oliver Flossmann, Mark A Little, Paul O'Hara, Pirow Bekker, David Jayne
INTRODUCTION: The treatment of ANCA associated vasculitis (AAV) aims to suppress disease activity and prevent subsequent disease flare. We explored the association of early disease control with long-term outcomes to validate early disease control as end-points for future clinical trials. METHODS: Data from four inception trials (CYCAZAREM, NORAM, MEPEX & CYCLOPS) and subsequent long-term registry data were studied. Clinical parameters at baseline, three and six months were assessed to study the risk of death and end stage renal failure (ESRF)...
November 12, 2018: Arthritis & Rheumatology
Riechers Elke, Niklas Baerlecken, Xenofon Baraliakos, Katrin Achilles-Mehr Bakhsh, Peer Aries, Bettina Bannert, Klaus Becker, Jan Brandt-Jürgens, Jürgen Braun, Boris Ehrenstein, Hans-Hartwig Euler, Martin Fleck, Reinhard Hein, Kirsten Karberg, Lars Köhler, Torsten Matthias, Regina Max, Adelheid Melzer, Dirk Meyer-Olson, Jürgen Rech, Karin Rockwitz, Martin Rudwaleit, Reinhold E Schmidt, Eva Schweikhard, Joachim Sieper, Carsten Stille, Ulrich von Hinüber, Peter Wagener, Heike-Franziska Weidemann, Silke Zinke, Torsten Witte
OBJECTIVES: Autoantibodies against CD74 (anti-CD74) are associated with ankylosing spondylitis. InterSpA is a multicenter study conducted to compare sensitivity and specificity of anti-CD74 and HLA-B27 in patients with non-radiographic axial spondyloarthritis (nr-axSpA). METHODS: Patients aged 18-45 years with inflammatory back pain of ≤2 years duration and clinical suspicion of axSpA were recruited. HLA-B27 genotyping and MRI of sacroiliac joints were performed in all patients...
November 12, 2018: Arthritis & Rheumatology
Ankit Mahendra, Xingyu Yang, Shaza Abnouf, Jay R T Adolacion, Daechan Park, Sanam Soomro, Jason Roszik, Cristian Coarfa, Gabrielle Romain, Keith Wanzeck, S Louis Bridges, Amita Aggarwal, Peng Qiu, Sandeep K Agarwal, Chandra Mohan, Navin Varadarajan
OBJECTIVE: To obtain the comprehensive transcriptome profile of human citrulline-specific B cells from patients diagnosed with rheumatoid arthritis (RA). METHODS: Citrulline and hemagglutinin (HA) specific B cells were flow-sorted using peptide-streptavidin conjugates from peripheral blood of RA patients and healthy individuals respectively. Transcriptome profile of the sorted cells was obtained by RNA-sequencing, and expression of key protein molecules was evaluated by aptamer-based SOMAscan assay and flow cytometry...
November 8, 2018: Arthritis & Rheumatology
David A Horwitz, Sean Bickerton, Michael Koss, Tarek M Fahmy, Antonio La Cava
OBJECTIVE: To develop a nanoparticle platform that can expand both CD4+ and CD8+ T regulatory cells (Tregs) in vivo for the suppression of autoimmune responses in systemic lupus erythematosus (SLE). METHODS: Poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IL-2 and TGF-β were coated with anti-CD2/CD4 antibodies and administered to mice with lupus-like disease induced by the transfer of DBA/2 T cells into (C57BL/6 x DBA/2)F1 (BDF1) mice. Peripheral frequency of Tregs was monitored ex vivo by flow cytometry...
November 8, 2018: Arthritis & Rheumatology
Isabelle Amigues, Aylin Tugcu, Cesare Russo, Jon T Giles, Rachelle Morgenstein, Afshin Zartoshti, Christian Schulze, Raul Flores, Sabahat Bokhari, Joan M Bathon
OBJECTIVES: To determine the prevalence and correlates of subclinical myocardial inflammation in rheumatoid arthritis (RA). METHODS: RA patients (n=119) without known cardiovascular disease (CVD) underwent cardiac 18-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET-CT). Myocardial FDG uptake was assessed visually and quantitatively by standardized uptake values (SUV). Multivariable linear regression was used to assess the associations of patient characteristics with myocardial SUV...
November 8, 2018: Arthritis & Rheumatology
Melissa N van Tok, Leonie M van Duivenvoorde, Ina Kramer, Peter Ingold, Sabina Pfister, Lukas Roth, Iris C Blijdorp, Marleen G H van de Sande, Joel D Taurog, Frank Kolbinger, Dominique L Baeten
OBJECTIVE: It remains unclear if and how inflammation and new bone formation in spondyloarthritis (SpA), are coupled. Here we assessed the hypothesis that IL-17A is a pivotal driver of both processes. METHODS: The effect of TNF and IL-17A on osteogenesis was tested in an osteoblast-differentiation assay using SpA fibroblast-like synoviocytes (FLS) differentiated with dexamethasone, beta-glycophosphatase and ascorbic acid. IL-17A blockade was performed in HLA-B27/Huβ2m transgenic rats, a model for spondyloarthritis, in a prophylactic and therapeutic setting...
November 2, 2018: Arthritis & Rheumatology
Cliff Rims, Hannes Uchtenhagen, Mariana J Kaplan, Carmelo Carmona-Rivera, Philip Carlucci, Katalin Mikecz, Adrienn Markovics, Jeffrey Carlin, Jane H Buckner, Eddie A James
OBJECTIVE: Recognition of citrullinated antigens such as vimentin, fibrinogen, and alpha-enolase is associated with rheumatoid arthritis (RA). Emerging data suggests that the matrix protein aggrecan is also recognized as a citrullinated antigen. The goal of this study was to directly visualize cit-aggrecan specific T cells and characterize them in subjects with RA. METHODS: Citrullinated aggrecan peptides with likely DRB1*04:01 binding motifs were predicted using a previously published scanning algorithm...
November 2, 2018: Arthritis & Rheumatology
Ioannis Kanakis, Ke Liu, Blandine Poulet, Behzad Javaheri, Rob J van 't Hof, Andrew A Pitsillides, George Bou-Gharios
BACKGROUND: Cartilage destruction in osteoarthritis (OA) is mediated mainly by MMPs and ADAMTSs. The therapeutic candidature of targeting aggrecanases has not yet been defined in joints where spontaneous OA arises due to genetic susceptibility, without a traumatic or load- induced aetiology such as the STR/Ort mouse. Nor do we know the long-term effect of aggrecanase inhibition on bone. METHODS: Using the STR/Ort spontaneously OA background, we have generated transgenic mice that overexpress [-1A]TIMP-3, either ubiquitously or conditionally in chondrocytes...
October 31, 2018: Arthritis & Rheumatology
Anja Schwenzer, Anne-Marie Quirke, Anna B Montgomery, Harlan R Sayles, Wolfgang Schlumberger, Jeffrey B Payne, Ted R Mikuls, Patrick J Venables, Kim S Midwood
Antibodies to citrullinated protein/peptide antigens (ACPA) are part of the diagnostic criteria for rheumatoid arthritis (RA). ACPA can be measured using generic tests, such as the CCP assays, using artificially generated synthetic peptides with no homology to known proteins, which provide good diagnostic sensitivity and specificity. Peptides from real auto-antigens, the so-called "fine specificities", tend to be of lower diagnostic sensitivity and are used primarily for research into disease pathogenesis, rather than clinical management...
October 31, 2018: Arthritis & Rheumatology
John G Hanly, Qiuju Li, Li Su, Murray B Urowitz, Caroline Gordon, Sang-Cheol Bae, Juanita Romero-Diaz, Jorge Sanchez-Guerrero, Sasha Bernatsky, Ann E Clarke, Daniel J Wallace, David A Isenberg, Anisur Rahman, Joan T Merrill, Paul R Fortin, Dafna D Gladman, Ian N Bruce, Michelle Petri, Ellen M Ginzler, M A Dooley, Kristjan Steinsson, Rosalind Ramsey-Goldman, Asad A Zoma, Susan Manzi, Ola Nived, Andreas Jonsen, Munther A Khamashta, Graciela S Alarcón, Ronald F van Vollenhoven, Cynthia Aranow, Meggan Mackay, Guillermo Ruiz-Irastorza, Manuel Ramos-Casals, S Sam Lim, Murat Inanc, Kenneth C Kalunian, Soren Jacobsen, Christine A Peschken, Diane L Kamen, Anca Askanase, Chris Theriault, Vernon Farewell
OBJECTIVES: To determine, in a multi-ethnic/racial, prospective SLE inception cohort, the frequency, attribution, clinical and autoantibody associations with lupus psychosis and the short and long-term outcome as assessed by physicians and patients. METHODS: Patients were evaluated annually for 19 neuropsychiatric (NP) events including psychosis. SLE disease activity 2000, SLICC/ACR damage index and SF-36 scores were collected. Time to event and linear regressions were used as appropriate...
October 30, 2018: Arthritis & Rheumatology
Antoine Néel, Marie Bucchia, Mélanie Néel, Gaelle Tilly, Aurélie Caristan, Michele Yap, Marie Rimbert, Sarah Bruneau, Marion Cadoux, Christian Agard, Maryvonne Hourmant, Pascal Godmer, Sophie Brouard, Céline Bressollette, Mohamed Hamidou, Regis Josien, Fadi Fakhouri, Nicolas Degauque
OBJECTIVE: To compare the effects of rituximab (RTX) and conventional immunosuppressants (CIS) on CD4+ , regulatory (Treg) and CD8+ T cells in ANCA-associated vasculitis (AAV). METHODS: Thorough immunophenotypic analysis of CD4+ , Treg and CD8+ cells of 51 AAV patients. Cytokine/chemokine production of in vitro stimulated CD8+ T cells was assessed using a multiplex immunoassay. AAV B cell impact on CD8+ T cell response was assessed using autologous and heterologous co-cultures...
October 30, 2018: Arthritis & Rheumatology
Elizabeth C Rosser, Hannah Lom, David Bending, Chantal L Duurland, Mona Bajaj-Elliott, Lucy R Wedderburn
OBJECTIVE: Evidence suggests that aberrant function of innate lymphoid cells (ILC), whose functional and transcriptional profile overlap with T helper (Th) cell subsets, contribute to immune-mediated pathologies. To date, analysis of Juvenile Idiopathic Arthritis (JIA) immune-pathology has concentrated on the contribution of CD4+ T-cells; we have previously identified an expansion of Th17 cells within the synovial fluid (SF) of JIA patients. Here, we extend this analysis to investigate a role for ILC and other IL-17 producing T-cell subsets...
October 22, 2018: Arthritis & Rheumatology
Ann E Warner, Kent K Huston
We read with interest the concise communication by Bernstein EJ et al. regarding practice patterns among rheumatologists with regard to screening for interstitial lung disease (ILD) in patients with systemic sclerosis. Referencing Suliman YA et al., they state that pulmonary function tests are "neither sensitive nor specific for the detection of ILD in this population." The primary message in the Suliman article is that PFTs yield a false negative rate of 62.5% for early detection of ILD in systemic sclerosis when HRCT is used as the gold standard...
October 22, 2018: Arthritis & Rheumatology
Elana J Bernstein, Dinesh Khanna, David J Lederer
We thank Drs. Warner and Huston for their interest in our manuscript. We agree that pulmonary function tests (PFTs) should not be "dismiss[ed]" as a screening test for "clinically significant" ILD in SSc. However, we disagree that the "significance of HRCT abnormalities suggestive of ILD in the absence of alterations in lung volumes or gas exchange remains unclear." SSc patients with 'normal' PFT parameters can still experience a clinically significant decline in their lung function over time...
October 22, 2018: Arthritis & Rheumatology
Michael D Lockshin
In this issue of Arthritis and Rheumatology Hanly et al. and the Systemic Lupus International Collaborating Clinics (SLICC) report that 1.5% of patients with systemic lupus erythematosus (SLE) experience an episode of psychosis within three years of diagnosis. Psychosis occurs early and is transient. Patients usually fully recover. They rarely relapse. In presenting this information, the paper shifts no paradigms about central nervous system (CNS) SLE, but it does provide answers to some common questions, and it offers lessons about clinical research that transcend the paper's face message...
October 22, 2018: Arthritis & Rheumatology
Atul Deodhar, Denis Poddubnyy, Cesar Pacheco-Tena, Carlo Salvarani, Eric Lespessailles, Proton Rahman, Pentti Järvinen, Juan Sanchez-Burson, Karl Gaffney, Eun Bong Lee, Eswar Krishnan, Silvia Santisteban, Xiaoqi Li, Fangyi Zhao, Hilde Carlier, John D Reveille
OBJECTIVE: To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (r-axSpA) and prior inadequate response or intolerance to 1 or 2 TNF inhibitors (TNFi). METHODS: In this randomized, double-blind placebo-controlled, Phase 3 trial, adult patients with inadequate response/intolerance to 1 or 2 TNFi and an established diagnosis of axSpA and fulfilling ASAS criteria for r-axSpA with radiographic sacroiliitis defined per modified NY criteria and ≥1 SpA feature were recruited and randomized 1:1:1 to placebo or 80-mg subcutaneous ixekizumab every 2 (IXEQ2W) or 4 (IXEQ4W) weeks, with a 80-mg or 160-mg starting dose...
October 20, 2018: Arthritis & Rheumatology
Lisa C Carlesso, Neil A Segal, Laura Frey-Law, Yuqing Zhang, Na Lu, Michael Nevitt, Core E Lewis, Tuhina Neogi
OBJECTIVES: Why some individuals develop pain with knee osteoarthritis (OA) is not clear. We sought to identify pain susceptibility phenotypes (PSPs) and their relation to incident persistent knee pain (PKP) 2 years later. METHODS: We identified individuals free of PKP from the Multicenter Osteoarthritis Study, a longitudinal cohort of older adults with or at risk of knee OA. Latent class analysis was used to determine PSPs that may contribute to development of PKP apart from structural pathology: widespread pain, poor sleep, psychological factors and quantitative sensory tests (QST) (i...
October 11, 2018: Arthritis & Rheumatology
Rikard Holmdahl
I read with great interest the article by Steen et al demonstrating that human plasma cell-derived monoclonal antibodies to post-translationally modified proteins recognize amino acid motifs rather than specific proteins (1). However, I believe some potentially misleading conclusions are drawn. In their paper, they report the isolation of IgG-secreting synovial plasma cells from one presumably high ACPA responder RA patient, followed by generation of the corresponding recombinant antibodies for evaluating their specificities and functions...
October 10, 2018: Arthritis & Rheumatology
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