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Arthritis & Rheumatology

Shefali K Sharma, M B Adarsh, Preksha Dwivedi, Manod, Mini P Singh, Varun Dhir, Shobha Sehgal, Sanjay Jain
Chang et al. need to be congratulated to show that Chikungunya (CHIK) is a public health issue that is not only limited to Asia and Africa but even a threat in the Americas. It is emerging as a global pandemic. We had 366 CHIK positive cases reported in and around Chandigarh from September 2016 to January 2017 as per the records of National Vector Disease Control Programme. We share our experience of 99 serologically confirmed cases of CHIK patients by NIV Chikungunya IgM Capture ELISA Kit, followed up for one year...
July 17, 2018: Arthritis & Rheumatology
Min Sun Shin, Youna Kang, Elizabeth R Wahl, Hong-Jai Park, Rossitza Lazova, Lin Leng, Mark Mamula, Smita Krishnaswamy, Richard Bucala, Insoo Kang
OBJECTIVE: High expression alleles of macrophage migration inhibitory factor (MIF) are linked genetically to SLE disease severity. The U1-snRNP (snRNP) immune complex containing U1-snRNP and anti-U1-snRNP antibodies, which are found in SLE, activates the NLRP3 inflammasome comprised of NLRP3, ASC, and procaspase-1 in human monocytes, leading to the production of IL-1β. The role of the snRNP immune complex in upregulating the MIF and its interface with the NLRP3 inflammasome were investigated...
July 15, 2018: Arthritis & Rheumatology
Cynthia Louis, Devi Ngo, Damian B D'Silva, Jacinta Hansen, Louisa Phillipson, Helene Jousset, Patrizia Novello, David Segal, Kate E Lawlor, Christopher J Burns, Ian P Wicks
OBJECTIVE: The production of class-switched high-affinity autoantibodies derived from organised germinal centers (GC) is a hallmark of many autoimmune inflammatory diseases, including rheumatoid arthritis (RA). TANK-binding kinase 1 (TBK1) is a serine-threonine kinase involved in the maturation of GC T follicular B helper cells (TFH ) downstream of inducible T cell costimulator (ICOS) signalling. We therefore assessed the therapeutic potential of TBK1 inhibition using a small molecule inhibitor - known as WEHI-112 - in antibody dependent models of inflammatory arthritis...
July 15, 2018: Arthritis & Rheumatology
Joseph D Croft
Herbert Kaplan died peacefully with his family by his side in his home at Loomis Village, South Hadley, MA on June 23, 2018 at the age of 88. He was the son of a high school math teacher and a mother who remained at home to care for three children. He graduated with honors from the University of Oklahoma and received his MD degree from Albany Medical College and his post graduate training at Duke University Hospital and Yale-New Haven Hospital. This article is protected by copyright. All rights reserved.
July 15, 2018: Arthritis & Rheumatology
Jaime A Cardona-Ospina, Alfonso J Rodríguez-Morales, Maria G Teixeira, Patrick Gérardin
We read with interest the manuscript by Chang et al entitled "Frequency of Chronic Joint Pain Following Chikungunya Virus Infection" (1). Although it was previously commented by Mogami et al (2), we want to underline the enrollment of the patients and the definition of acute and chronic chikungunya virus (CHIKV) disease. Patients were recruited after healthcare referral because of suspected CHIKV infection, and confirmed cases were considered if either CHIKV-specific IgM or CHIKV-specific IgG were positive...
July 13, 2018: Arthritis & Rheumatology
Tomasz Janczi, Böhm B Beate, Yuliya Fehrl, Pangrazio DeGiacomo, Raimund W Kinne, Harald Burkhardt
OBJECTIVES: To investigate mechanisms underlying the capability of ADAM15 to transform FasL-mediated death inducing signals into pro-survival activation of Src and focal adhesion kinase (FAK) in rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Caspase-3/7 activity and apoptosis rate were determined in RASFs and ADAM15-transfected T/C28a4 cells upon Fas/CD95 triggering using enzyme assays and annexin-V staining. Phosphorylated Src and FAK was analyzed by immunoblotting...
July 13, 2018: Arthritis & Rheumatology
Patrick Gérardin, Jaime A Cardona-Ospina, Alfonso J Rodríguez-Morales
We read the paper by Chang et al demonstrating the absence of detectable virus in the synovial fluid of chikungunya arthritic patients (1). Although tissue biopsies were not performed, the authors provide compelling arguments against the hypothesis of viral persistence in the pathophysiology of chikungunya arthritis (2), based on the negativity of both synovial fluid culture and proteomic analysis. Furthermore, given the presumption of efficacy of DMARDs, the authors conclude, as others before them, that autoimmunity may be the leading contributor to chikungunya arthritis (2)...
July 13, 2018: Arthritis & Rheumatology
Aileen Y Chang, Patrick Reid, Liliana Encinales, Jeffrey M Bethony, Gary L Simon, Gary S Firestein
We thank Gérardin et. al., for sharing their thoughts on potential mechanisms that might contribute to the pathogenesis of chikungunya arthritis. Although, we did not observe anti-citrullinated cyclic peptide (anti-CCP) antibodies in our cohort, post-translational modifications including citrullination, carbamylation, and malondialdehyde-acetaldehyde are emerging as having important clinical and mechanistic significance in rheumatoid arthritis. Therefore, one can postulate these modifications may have clinical and mechanistic significance in the context of viral-induced arthritis as well and further research into these mechanisms in chikungunya arthritis is needed...
July 13, 2018: Arthritis & Rheumatology
Aileen Y Chang, Liliana Encinales, Gary S Firestein, Gary L Simon, Jeffrey M Bethony
We thank Sharma et al. and Cardona-Ospina et al. for sharing their experience and discussion. One of the limitations of our evaluation of the cohort was that we have not yet determined the incidence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies in all 485 patients. This will be a valuable assessment to perform. However, RF and anti-CCP antibodies were measured in a subset of chikungunya arthritis patients1 and no CHIKV arthritis patients had elevated anti-CCP antibodies, 9% had IgM-RF antibodies, and 12% had IgG-RF antibodies...
July 12, 2018: Arthritis & Rheumatology
Sarah Pringle, Xiaoyan Wang, Gwenny M P J Verstappen, Janneke H Terpstra, Clarence K Zhang, Aiqing He, Vishal Patel, Rhiannon E Jones, Duncan M Baird, Fred K L Spijkervet, Arjan Vissink, Hendrika Bootsma, Robert P Coppes, Frans G M Kroese
OBJECTIVE: A major characteristic of the autoimmune disease primary Sjögren's syndrome (pSS) is salivary gland (SG) hypofunction. Resident salivary gland stem cell (SGSC) inability to maintain homeostasis and saliva production has never been explained, and limits our comprehension of mechanisms underpinning pSS. METHODS: SGSCs were isolated from parotid biopsies of controls and patients classified as pSS or incomplete pSS, according to ACR-EULAR criteria. Self-renewal and differentiation assays determined SGSC regenerative potential, RNA was extracted for RNASeq analysis, STELA analysis employed to determine telomere length, and frozen tissue used for immunohistochemical analysis...
July 9, 2018: Arthritis & Rheumatology
Jun Won Park, Minjung Kim, Jeong Seok Lee, You-Jung Ha, Jin Kyun Park, Eun Ha Kang, Yunjong Lee, Yeong Wook Song, Eun Young Lee
OBJECTIVE: To investigate the impact tumour necrosis factor inhibitor (TNFi) treatment and inflammation control on radiographic progression in early ankylosing spondylitis (AS) over 4 years. METHODS: In total, 215 early AS patients (symptom duration < 10 years) treated with TNFi (TNFi group, n = 135) or nonsteroidal anti-inflammatory drugs (NSAIDs) (control group, n = 80) were included. Two blinded readers assessed radiographic progression using modified Stoke Ankylosing Spondylitis Spine Scores (mSASSS)...
July 8, 2018: Arthritis & Rheumatology
Heather Evans-Marin, Rebecca Rogier, Sergei B Koralov, Julia Manasson, Debbie Roeleveld, Peter M van der Kraan, Jose U Scher, Marije I Koenders, Shahla Abdollahi-Roodsaz
OBJECTIVE: The intestinal microbiota has been associated with the development of inflammatory arthritis. The aim of this study was to dissect intestinal mucosal immune responses in the preclinical phase of arthritis and determine the requirement of Th17 cells, beyond the cytokine interleukin-17 (IL-17), for arthritis development. We further examined whether the involvement of Th17 cells in arthritis depends on the host microbiota. METHODS: We analyzed mucosal T cell production of IL-17, IFNγ, TNFα, IL-22 and GM-CSF by flow cytometry and Luminex in mice immunized for the induction of collagen-induced arthritis (CIA) before arthritis onset...
July 5, 2018: Arthritis & Rheumatology
Katie Streicher, Sriram Sridhar, Mike Kuziora, Christopher A Morehouse, Brandon W Higgs, Yinong Sebastian, Christopher J Groves, Fernanda Pilataxi, Philip Z Brohawn, Ronald Herbst, Koustubh Ranade
OBJECTIVES: B cells impact systemic sclerosis (SSc) progression through multiple pathogenic mechanisms. CD19 inhibition in mice reduced skin thickness, collagen production, and autoantibody levels, consistent with CD19 expression on plasma cells (PCs), the source of antibody production. Plasma cell depletion could effectively reduce collagen deposition and inflammation in SSc; therefore, we investigated effects on SSc disease activity. METHODS: A PC gene signature was evaluated in SSc skin biopsies in two phase I clinical trials...
June 29, 2018: Arthritis & Rheumatology
Antoine G Sreih, Rana Ezzedine, Lin Leng, Juan Fan, Jie Yao, Duncan Reid, Marta Piecychna, Simon Carette, David Cuthbertson, Paul Dellaripa, Gary S Hoffman, Nader A Khalidi, Curry L Koening, Carol A Langford, Alfred Mahr, Carol A McAlear, Kathleen Maksimowicz-Mckinnon, Paul A Monach, Philip Seo, Ulrich Specks, William St Clair, John H Stone, Steven R Ytterberg, Jeffrey Edberg, Peter A Merkel, Richard Bucala
OBJECTIVE: This study examined the association between Macrophage Migration Inhibitory Factor (MIF) promoter polymorphisms and granulomatosis with polyangiitis (GPA), and MIF's role in a murine model of granulomatous vasculitis. METHODS: The human study involved 1077 patients with GPA and controls. Genotyping for the MIF -794 CATT5-8 promoter microsatellite (rs5844572) was performed by capillary electrophoresis. MIF promoter CATT-length dependent expression in response to β-glucan was assessed by gene reporter assays...
June 28, 2018: Arthritis & Rheumatology
Daniel Toro-Domínguez, Jordi Martorell-Marugán, Daniel Goldman, Michelle Petri, Pedro Carmona-Sáez, Marta E Alarcón-Riquelme
OBJECTIVES: The highly heterogeneous clinical presentation of lupus is characterized by the unpredictable appearance of flares of disease activity and important organ damage. Attempts to stratify lupus patients have been limited to clinical information, leading to unsuccessful clinical trials and controversial research results. Our aim was to develop and validate a robust method to stratify patients with lupus according to longitudinal disease activity and whole-genome gene expression data in order to establish subgroups of patients who share disease progression mechanisms...
June 25, 2018: Arthritis & Rheumatology
Yumi Tsuchida, Shuji Sumitomo, Kazuyoshi Ishigaki, Mineto Ota, Haruka Tsuchiya, Kensuke Yamaguchi, Yasuo Nagafuchi, Hirofumi Shoda, Akari Suzuki, Yuta Kochi, Keishi Fujio, Kazuhiko Yamamoto
In "CD4+ and B lymphocyte expression quantitative traits at rheumatoid arthritis risk loci in untreated early arthritis: implications for causal gene identification," Thalayasingam et al (1) reported that the 6p23 locus, associated with rheumatoid arthritis (RA), has a B cell-specific eQTL effect on CD83. The B cell-specific eQTL effect at this locus is robust and has also been reported in other studies (2), and this locus presumably contributes to the pathogenesis of RA by decreasing the expression of CD83 on B cells...
June 25, 2018: Arthritis & Rheumatology
Eva C Schwaneck, Regina Renner, Lara Junker, Hermann Einsele, Ottar Gadeholt, Eva Geissinger, Stefan Kleinert, Michael Gernert, Hans-Peter Tony, Marc Schmalzing
OBJECTIVE: Up to one third of patients with T-cell large granular lymphocyte leukemia (T-LGL-leukemia) display symptoms of rheumatoid arthritis (RA). In Crohn's disease and in psoriasis treatment with TNFα-inhibitors is associated with hepatosplenic γδT-cell-lymphoma and with clonal expansion of γδT-cells, respectively. Here, we determine the prevalence of clonal T-LGL cells in patients with RA and define risk factors for this rare hematologic malignancy. METHODS: 529 RA-patients were recruited between November, 2013 and August, 2015...
June 25, 2018: Arthritis & Rheumatology
John G Hanly, Elizabeth Kozora, Steven Beyea, Julius Birnbaum
The American College of Rheumatology (ACR) case definitions for 19 neuropsychiatric syndromes constitute a comprehensive classification of nervous system events in SLE patients. However, additional strategies are needed to determine whether a neurological syndrome is attributable to SLE versus a competing co-morbidity. Cognitive function is a clinical surrogate of overall brain health with applications in both diagnosis and determination of clinical outcomes. Ischemic and inflammatory mechanisms are both key components of the immunopathogenesis of NPSLE, including abnormalities of the blood-brain-barrier and autoantibody mediated production of pro-inflammatory cytokines...
June 21, 2018: Arthritis & Rheumatology
Philip J Titcombe, Gustaf Wigerblade, Natalie Sippl, Na Zhang, Anna K Shmagel, Peter Sahlström, Yue Zhang, Laura O Barsness, Yogita Ghodke-Puranik, Azar Baharpoor, Monika Hansson, Lena Israelsson, Karl Skriner, Timothy B Niewold, Lars Klareskog, Camilla I Svensson, Khaled Amara, Vivianne Malmström, Daniel L Mueller
OBJECTIVE: Anti-citrullinated protein antibodies (ACPA) have proven highly useful as biomarkers in rheumatoid arthritis (RA). However, the composition and functionality of the associated autoreactive B cell repertoire have not been directly assessed. We aimed to selectively investigate citrullinated autoantigen-specific B cell receptors (BCRs) involved in RA and initiate studies on their pathogenicity. METHODS: A University of Minnesota ACPA+ RA cohort (n = 89 subjects) provided blood samples...
June 21, 2018: Arthritis & Rheumatology
Serra E Elliott, Sarah Kongpachith, Nithya Lingampalli, Julia Z Adamska, Bryan J Cannon, Rong Mao, Lisa K Blum, William H Robinson
OBJECTIVE: Rheumatoid arthritis (RA) is characterized by anti-citrullinated protein antibodies (ACPAs), nevertheless, the origin, specificity, and functional properties of ACPAs remain poorly understood. To characterize the evolution of ACPAs, we sequenced the plasmablast antibody repertoire at serial timepoints in subjects with established RA. METHODS: Blood samples were obtained at up to four timepoints from eight anti-CCP+ individuals with established RA. We single-cell sorted CD19+CD3-IgD-CD14-CD20-CD27+CD38++ plasmablasts and co-stained with citrullinated-peptide tetramers to identify ACPA-expressing plasmablasts...
June 21, 2018: Arthritis & Rheumatology
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