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By Wei No
Bernadette M Lynch, Edward P Stern, Voon Ong, Mark Harber, Aine Burns, Christopher P Denton
The UK Scleroderma Study Group developed guidelines on the diagnosis and management of scleroderma renal crisis (SRC) based on best available evidence and clinical experience. SRC is characterised by the acute onset of severe hypertension and acute kidney injury. Current strategies to reduce the associated morbidity and mortality include identifying at risk patients to aid early diagnosis. ACE inhibitor therapy should be lifelong in all patients, regardless of whether they require renal replacement therapy...
September 2016: Clinical and Experimental Rheumatology
Eleonora Bellucci, Riccardo Terenzi, Giuliana Maria Concetta La Paglia, Stefano Gentileschi, Alessandra Tripoli, Chiara Tani, Alessia Alunno
Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic synovial inflammation leading to joint destruction and bone erosions. Although the pathogenic mechanisms underlying the disease are not fully elucidated, it is known that genetic susceptibility and environmental factors trigger an abnormal autoimmune response. Potentially, any organ and tissue could be affected by RA and the increased cardiovascular (CV) risk represents the major complication responsible for a worse prognosis. In this setting, the shared pathogenic mechanisms between RA pathogenesis and accelerated atherosclerosis further strengthen the rationale for a treat-to-target strategy with synthetic and biologic disease modifying anti-rheumatic drugs...
September 2016: Clinical and Experimental Rheumatology
Sheikh Fayaz Ahmad, Mushtaq Ahmad Ansari, Ahmed Nadeem, Khairy M A Zoheir, Saleh A Bakheet, Abdulaziz M S Alsaad, Othman A Al-Shabanah, Sabry M Attia
We set out to investigate the influence of STA-21, a dynamic STAT-3 inhibitor, on the expansion and progression of rheumatoid arthritis (RA), and to determine its potential mechanisms of action in a mouse model of collagen antibody-induced arthritis (CAIA). To this end, arthritis was induced via intravenous (IV) injection of Balb/c mice with a cocktail of antibodies directed against type II collagen (1.5μg/mouse, IV), followed by lipopolysaccharide (LPS) at a dose of (25μg/mouse, i.p.) on day 3. Mice were then left untreated or were simultaneously treated with STA-21 (0...
October 3, 2016: Immunobiology
María-José Barrera, Sergio Aguilera, Isabel Castro, Juan Cortés, Verónica Bahamondes, Andrew F G Quest, Claudio Molina, Sergio González, Marcela Hermoso, Ulises Urzúa, Cecilia Leyton, María-Julieta González
Salivary gland (SG) acinar-cells are susceptible to endoplasmic reticulum (ER) stress related to their secretory activity and the complexity of synthesized secretory products. SGs of Sjögren's syndrome patients (SS)-patients show signs of inflammation and altered proteostasis, associated with low IRE1α/XBP-1 pathway activity without avert increases in apoptosis. Acinar-cells may avoid apoptosis by activation of the ATF6α pathway and ER-associated protein degradation (ERAD). The aim of this study was to evaluate the role of pro-inflammatory cytokines in ATF6α pathway/ERAD activation and cell viability in labial salivary glands (LSG) of SS-patients...
July 23, 2016: Journal of Autoimmunity
Patrick Verschueren, Diederik De Cock, Luk Corluy, Rik Joos, Christine Langenaken, Veerle Taelman, Frank Raeman, Isabelle Ravelingien, Klaas Vandevyvere, Jan Lenaerts, Elke Geens, Piet Geusens, Johan Vanhoof, Anne Durnez, Jan Remans, Bert Vander Cruyssen, Els Van Essche, An Sileghem, Griet De Brabanter, Johan Joly, Sabrina Meyfroidt, Kristien Van der Elst, Rene Westhovens
OBJECTIVES: Combining disease-modifying antirheumatic drugs (DMARDs) with glucocorticoids (GCs) is an effective treatment strategy for early rheumatoid arthritis (ERA), yet the ideal schedule and feasibility in daily practice are debated. We evaluated different DMARD combinations and GC remission induction schemes in poor prognosis patients; and methotrexate (MTX) with or without GC remission induction in good prognosis patients, during the first treatment year. METHODS: The Care in ERA (CareRA) trial is a 2-year investigator-initiated randomised pragmatic open-label superiority trial comparing remission induction regimens in a treat-to-target approach...
July 18, 2016: Annals of the Rheumatic Diseases
Florenzo Iannone, Marilina Tampoia, Margherita Giannini, Giuseppe Lopalco, Luca Cantarini, C Danilo Villalta, Mauro Galeazzi, Giovanni Lapadula
OBJECTIVES: Anti-cyclic citrullinated peptide antibodies (anti-CCP) are a serological marker of rheumatoid arthritis (RA), and also have a prognostic value for more aggressive disease. Whether anti-CCP levels may change during treatment according to clinical response is matter of debate. Likewise, it is unknown whether different biological drugs have peculiar effects on anti-CCP levels. This study aimed to investigate changes in anti-CCP serum levels in RA patients on biological drugs with different mechanism of action...
May 2016: Clinical and Experimental Rheumatology
Astrid Rasmussen, Lida Radfar, David Lewis, Kiely Grundahl, Donald U Stone, C Erick Kaufman, Nelson L Rhodus, Barbara Segal, Daniel J Wallace, Michael H Weisman, Swamy Venuturupalli, Biji T Kurien, Christopher J Lessard, Kathy L Sivils, R Hal Scofield
OBJECTIVE: The diagnosis of SS is often difficult and many patients are symptomatic for years with other diagnoses before confirmation of SS. Our aim was to determine whether overlapping clinical and serologic features with RA and SLE may in part drive the misdiagnoses. METHODS: A total of 1175 sicca patients were evaluated in a multidisciplinary clinic and classified as having SS based on the American-European Consensus Group Criteria. They were interrogated for a past history of suspicion or diagnosis of RA, SLE or SSc...
July 2016: Rheumatology
Alain Saraux, Jacques-Olivier Pers, Valérie Devauchelle-Pensec
Primary Sjögren syndrome (pSS) is a progressive autoimmune disease characterized by sicca and systemic manifestations. In this Review, we summarize the available data on topical and systemic medications, according to clinical signs and disease activity, and we describe the ongoing studies using biologic drugs in the treatment of pSS. Expanding knowledge about the epidemiology, classification criteria, systemic activity scoring (ESSDAI) and patient-reported outcomes (ESSPRI) is driving active research. Treatment decisions are based on the evaluation of symptoms and extraglandular manifestations...
August 2016: Nature Reviews. Rheumatology
Anna K Bird, Nida Meednu, Jennifer H Anolik
PURPOSE OF REVIEW: Our understanding of the physiological and pathogenic functions of B cells in systemic lupus erythematosus (SLE) and Primary Sjögren's syndrome (pSS) continues to expand. In this review, we discuss novel insights published in the last 18 months into the roles of B cells in systemic autoimmunity. RECENT FINDINGS: Data have continued to expand regarding the diverse mechanisms by which innate immune signals including Toll-like receptors (TLRs) regulate the B cell compartment...
September 2015: Current Opinion in Rheumatology
Takashi Maehara, Hamid Mattoo, Miho Ohta, Vinay S Mahajan, Masafumi Moriyama, Masaki Yamauchi, Jefte Drijvers, Seiji Nakamura, John H Stone, Shiv S Pillai
OBJECTIVES: IgG4-related disease (IgG4-RD) is a chronic, systemic, inflammatory condition of unknown aetiology. We have recently described clonally expanded circulating CD4(+) cytotoxic T lymphocytes (CTLs) in IgG4-RD that infiltrate affected tissues where they secrete interleukin (IL)-1β and transforming growth factor -β1 (TGF-β1). In this study, we sought to examine the role of CD4(+) CTLs in the pathogenesis of IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) and to determine whether these cells secrete interferon-gamma (IFN-γ) at lesional sites...
June 29, 2016: Annals of the Rheumatic Diseases
Margherita Sisto, Loredana Lorusso, Sabrina Lisi
Toll-like receptors (TLRs) are pattern recognition receptors linking innate and adaptive immune responses, which resulted overexpressed in primary Sjögren's syndrome (pSS). Interleukin-15 (IL-15) is a pro-inflammatory cytokine which was recently demonstrated to be involved in pSS pathogenesis. The study was undertaken to clarify whether TLR2 is involved in the production of IL-15 in human salivary gland epithelial cells (SGEC) from pSS patients. SGEC primary cell cultures were established from pSS minor salivary gland tissues explanted from patients with a sure diagnosis of SS...
June 3, 2016: Clinical and Experimental Medicine
Sarah Benchabane, Abdelhalim Boudjelida, Ryma Toumi, Houda Belguendouz, Pierre Youinou, Chafia Touil-Boukoffa
Sjögren's syndrome (SS) is an autoimmune epithelitis characterized by mononuclear cell (MNC) infiltration of the lacrimal and salivary glands (SG), as well as the presence of serum autoantibodies. This condition is a growing public health concern in Algeria. Herein, we sought to determine if the levels of interleukin (IL)-6, IL-17A, and nitric oxide (NO), were correlated with the extent of MNC infiltration. The expression of inducible NO synthase (NOS2) and CD68 was measured in the SG of all patients, but not in those of the normal controls (NCs)...
September 2016: International Journal of Immunopathology and Pharmacology
Lilian Vasaitis, Christer Sundström, Carin Backlin, Gunnel Nordmark, Eva Baecklund
BACKGROUND: IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder, which may affect many organs, and often comes to clinical attention due to tumor-like organ swelling or is identified incidentally by specific biopsy findings. Typical histopathology of IgG4-RD is lymphoplasmacytic infiltration rich in IgG4 + plasma cells (PCs), storiform fibrosis, and obliterative phlebitis. Patients with sicca symptoms can be misdiagnosed as primary Sjögren's syndrome (pSS) instead of IgG4-RD because of clinical and histopathological similarities...
May 19, 2016: Acta Oncologica
M Hifinger, M Hiligsmann, S Ramiro, V Watson, J L Severens, B Fautrel, T Uhlig, R van Vollenhoven, P Jacques, J Detert, J Canas da Silva, C A Scirè, F Berghea, L Carmona, M Péntek, A Keat, A Boonen
OBJECTIVE: To compare the value that rheumatologists across Europe attach to patients' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis. METHODS: In a discrete choice experiment, European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity. Treatments differed in five attributes: efficacy (improvement and achieved state on disease activity), safety (probability of serious adverse events), patient's preference (level of agreement), medication costs and cost-effectiveness (incremental cost-effectiveness ratio (ICER))...
May 17, 2016: Annals of the Rheumatic Diseases
Ryan W Gan, M Kristen Demoruelle, Kevin D Deane, Michael H Weisman, Jane H Buckner, Peter K Gregersen, Ted R Mikuls, James R O'Dell, Richard M Keating, Tasha E Fingerlin, Gary O Zerbe, Michael J Clare-Salzler, V Michael Holers, Jill M Norris
OBJECTIVES: Previously, we found that omega-3 fatty acids (n-3 FAs) were inversely associated with anti-cyclic citrullinated peptide (anti-CCP) positivity in participants at risk for future rheumatoid arthritis (RA). We investigated whether n-3 FAs were also associated with rheumatoid factor (RF) positivity and whether these associations were modified by shared epitope (SE) positivity. METHODS: The Studies of the Etiology of RA (SERA) cohort includes RA-free participants who are at increased risk for RA...
May 17, 2016: Annals of the Rheumatic Diseases
Lena Bugge Nordberg, Siri Lillegraven, Elisabeth Lie, Anna-Birgitte Aga, Inge Christoffer Olsen, Hilde Berner Hammer, Till Uhlig, Maria Karolina Jonsson, Désirée van der Heijde, Tore K Kvien, Espen Andre Haavardsholm
OBJECTIVES: To compare the presentation of seropositive and seronegative early rheumatoid arthritis (RA) in disease-modifying antirheumatic drug (DMARD)-naïve patients classified according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria. METHODS: All patients had symptom duration from first swollen joint <2 years and were DMARD naïve with an indication for DMARD treatment. Patients were stratified as seropositive (positive rheumatoid factor (RF)+ and/or anticitrullinated peptide antibody (ACPA)+) or seronegative (RF- and ACPA-), and disease characteristics were compared between groups...
April 19, 2016: Annals of the Rheumatic Diseases
O Alvarez-Garcia, M Olmer, R Akagi, Y Akasaki, K M Fisch, T Shen, A I Su, M K Lotz
OBJECTIVE: Aging is a main risk factor for the development of osteoarthritis (OA) and the molecular mechanisms underlying the aging-related changes in articular cartilage include increased mammalian target of rapamycin (mTOR) signaling and defective autophagy. REDD1 is an endogenous inhibitor of mTOR that regulates cellular stress responses. In this study we measured REDD1 expression in normal, aged and OA cartilage and assessed REDD1 function in human and mouse articular chondrocytes...
September 2016: Osteoarthritis and Cartilage
Melissa E Munroe, Rufei Lu, Yan D Zhao, Dustin A Fife, Julie M Robertson, Joel M Guthridge, Timothy B Niewold, George C Tsokos, Michael P Keith, John B Harley, Judith A James
OBJECTIVES: The relationship of immune dysregulation and autoantibody production that may contribute to systemic lupus erythematosus (SLE) pathogenesis is unknown. This study evaluates the individual and combined contributions of autoantibodies, type I interferon (IFN-α) activity, and IFN-associated soluble mediators to disease development leading to SLE. METHODS: Serial serum specimens from 55 individuals collected prior to SLE classification (average timespan=4...
January 25, 2016: Annals of the Rheumatic Diseases
Michael Hughes, Ariane L Herrick
Digital ulcers (DUs) are a common visible manifestation of the progressive vascular disease that characterizes the SSc disease process. DUs not only impact significantly on patients' quality of life and hand function, but are also a biomarker of internal organ involvement and of disease severity. The aetiology of (digital) vascular disease in SSc is multifactorial, and many of these factors are potentially amenable to therapeutic intervention. The management of DU disease in SSc is multifaceted. Patient education and non-pharmacological interventions (e...
April 19, 2016: Rheumatology
Guangyong Peng, Zhong Guo, Yukiko Kiniwa, Kui Shin Voo, Weiyi Peng, Tihui Fu, Daniel Y Wang, Yanchun Li, Helen Y Wang, Rong-Fu Wang
CD4+ regulatory T (Treg) cells have a profound ability to suppress host immune responses, yet little is understood about how these cells are regulated. We describe a mechanism linking Toll-like receptor (TLR) 8 signaling to the control of Treg cell function, in which synthetic and natural ligands for human TLR8 can reverse Treg cell function. This effect was independent of dendritic cells but required functional TLR8-MyD88-IRAK4 signaling in Treg cells. Adoptive transfer of TLR8 ligand-stimulated Treg cells into tumor-bearing mice enhanced anti-tumor immunity...
August 26, 2005: Science
2016-05-01 23:17:59
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