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Rheumatoid Arthritis: HELP
Articles from University of Athens
Based on 179 articles published since 2008
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These are the 179 published articles about Arthritis, Rheumatoid that originated from University of Athens during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8
1 Guideline Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren's syndrome. 2017

Fisher, Benjamin A / Jonsson, Roland / Daniels, Troy / Bombardieri, Michele / Brown, Rachel M / Morgan, Peter / Bombardieri, Stefano / Ng, Wan-Fai / Tzioufas, Athanasios G / Vitali, Claudio / Shirlaw, Pepe / Haacke, Erlin / Costa, Sebastian / Bootsma, Hendrika / Devauchelle-Pensec, Valerie / Radstake, Timothy R / Mariette, Xavier / Richards, Andrea / Stack, Rebecca / Bowman, Simon J / Barone, Francesca / Anonymous4170890. ·Rheumatology Research Group and Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), University of Birmingham, Birmingham, UK. · Department of Rheumatology, University Hospitals Birmingham NHS Trust, Birmingham, UK. · Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway. · Department of Rheumatology, Haukeland University Hospital, Bergen, Norway. · Department of Orofacial Sciences, University of California San Francisco, San Francisco California, USA. · Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, London, UK. · Department of Pathology, University Hospitals Birmingham NHS Trust, Birmingham, UK. · Department of Pathology, King's College London, London, UK. · Rheumatology Unit, University of Pisa, Pisa, Italy. · Musculoskeletal Research Group and NIHR Biomedical Research Centre in Ageing and Chronic Diseases, Newcastle University, Newcastle, UK. · Department of Pathophysiology, University of Athens, Athens, Greece. · Section of Rheumatology, Casa di Cura di Lecco, Lecco, Italy. · Department of Oral Medicine, King's College London, London, UK. · Department of Pathology, University of Groningen, Groningen, The Netherlands. · Department of Pathology, Brest University Hospital, Brest, France. · Department of Rheumatology and Clinical Immunology, University of Groningen, Groningen, The Netherlands. · Rheumatology Department, Cavale Blanche Hospital and Brest Occidentale University, ER129, Brest, France. · Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands. · Rheumatology Department, Université Paris-Sud, Assistance Publique-Hôpitaux de Paris, INSERM U1184, Le Kremlin-Bicêtre, France. · Department of Oral Medicine, Dental Hospital, Birmingham, UK. ·Ann Rheum Dis · Pubmed #27965259.

ABSTRACT: Labial salivary gland (LSG) biopsy is used in the classification of primary Sjögren's syndrome (PSS) and in patient stratification in clinical trials. It may also function as a biomarker. The acquisition of tissue and histological interpretation is variable and needs to be standardised for use in clinical trials. A modified European League Against Rheumatism consensus guideline development strategy was used. The steering committee of the ad hoc working group identified key outstanding points of variability in LSG acquisition and analysis. A 2-day workshop was held to develop consensus where possible and identify points where further discussion/data was needed. These points were reviewed by a subgroup of experts on PSS histopathology and then circulated via an online survey to 50 stakeholder experts consisting of rheumatologists, histopathologists and oral medicine specialists, to assess level of agreement (0-10 scale) and comments. Criteria for agreement were a mean score ≥6/10 and 75% of respondents scoring ≥6/10. Thirty-nine (78%) experts responded and 16 points met criteria for agreement. These points are focused on tissue requirements, identification of the characteristic focal lymphocytic sialadenitis, calculation of the focus score, identification of germinal centres, assessment of the area of leucocyte infiltration, reporting standards and use of prestudy samples for clinical trials. We provide standardised consensus guidance for the use of labial salivary gland histopathology in the classification of PSS and in clinical trials and identify areas where further research is required to achieve evidence-based consensus.

2 Editorial Limited efficacy of targeted treatments in Sjögren's syndrome: why? 2018

Tzioufas, Athanasios G / Goules, Andreas V. ·Pathophysiology Department, Athens School of Medicine, Athens, Greece. agtzi@med.uoa.gr. · Pathophysiology Department, Athens School of Medicine, Athens, Greece. ·Clin Exp Rheumatol · Pubmed #29998826.

ABSTRACT: -- No abstract --

3 Editorial Sjögren's syndrome: disease activity indexes! Do they make us better clinicians or technicians? 2018

Moutsopoulos, Haralampos M / Skopouli, Fotini N. ·School of Medicine, National and Kapodistrian University of Athens, Greece. hmoutsop@med.uoa.gr. · Harokopio University of Athens, Greece. ·Clin Exp Rheumatol · Pubmed #29846164.

ABSTRACT: -- No abstract --

4 Editorial Rheumatoid Arthritis and Atherosclerosis: Could Common Pathogenesis Translate Into Common Therapies? 2015

Lazaros, George / Tousoulis, Dimitrios. ·Cardiology Department, University of Athens Medical School, Hippokration General Hospital, Athens, Greece. ·Hellenic J Cardiol · Pubmed #26429370.

ABSTRACT: -- No abstract --

5 Review Lymphomagenesis in Sjögren's syndrome: Predictive biomarkers towards precision medicine. 2019

Goules, Andreas V / Tzioufas, Athanasios G. ·Department of Pathophysiology, School of Medicine, University of Athens, Mikras Asias Str 75, 115 27 Athens, Greece. · Department of Pathophysiology, School of Medicine, University of Athens, Mikras Asias Str 75, 115 27 Athens, Greece. Electronic address: agtzi@med.uoa.gr. ·Autoimmun Rev · Pubmed #30572133.

ABSTRACT: Sjögren's syndrome (SS) is characterized by B cell hyperactivity documented by the production of plethora of autoantibodies and a strong tendency for NHL of B cell origin. Classical predictors of lymphoma have been already proposed and proved their validity, including clinical, serological and histopathologic biomarkers. The process of lymphomagenesis is multistep and encompasses mechanisms of antigen driven selection of the BCR with RF activity and various genetic contributors implicated in B cell proliferation, cell growth and cell cycle control, enhanced by a complex milieu of cytokines and trophic agents that are abundant within the inflammatory lesion of minor salivary glands of SS patients. Extensive efforts in the basic research field have revealed several novel biomarkers for lymphoma prediction while the major cellular and molecular mechanisms of evolutionary transition of B cells towards malignancy are under investigation. In this review, we present the current data regarding the newly proposed biomarkers for SS associated lymphoma prediction and a hypothetical model of lymphomagenesis based on the emerging data.

6 Review One year in review 2018: Sjögren's syndrome. 2018

Argyropoulou, Ourania D / Valentini, Eleonora / Ferro, Francesco / Leone, Maria Comasia / Cafaro, Giacomo / Bartoloni, Elena / Baldini, Chiara. ·Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Greece. · Rheumatology Unit, University of Perugia, Italy. · Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy. · Rheumatology Unit, University of Perugia, Italy. elena.bartolonibocci@unipg.it. ·Clin Exp Rheumatol · Pubmed #30156536.

ABSTRACT: Sjögren's syndrome is a complex and potentially disabling slow progressive, systemic disorder. During the last twelve months several original and important contributions have been published on the pathogenesis, diagnosis and therapy of the disease. This review, following the others of this series is aimed at summarising some of the most significant studies that have been recently published. Regarding the pathogenesis, we will specifically focus on novel insights on miRNA, gut microbiota, adaptive and innate autoimmunity and animal models. Concerning novelties in pSS diagnosis, we will focus on salivary gland ultrasonography and histology. Finally, we will conclude with an update of the clinical manifestations of the disease and with an overview of the future therapies.

7 Review Systemic Inflammatory Response and Atherosclerosis: The Paradigm of Chronic Inflammatory Rheumatic Diseases. 2018

Arida, Aikaterini / Protogerou, Athanasios D / Kitas, George D / Sfikakis, Petros P. ·First Department of Propaedeutic and Internal Medicine and Joint Rheumatology Program, National and Kapodistrian University of Athens Medical School, GR-115 27 Athens, Greece. aridakater@yahoo.gr. · First Department of Propaedeutic and Internal Medicine and Joint Rheumatology Program, National and Kapodistrian University of Athens Medical School, GR-115 27 Athens, Greece. athanprot@gmail.com. · First Department of Propaedeutic and Internal Medicine and Joint Rheumatology Program, National and Kapodistrian University of Athens Medical School, GR-115 27 Athens, Greece. george.kitas@nhs.net. · First Department of Propaedeutic and Internal Medicine and Joint Rheumatology Program, National and Kapodistrian University of Athens Medical School, GR-115 27 Athens, Greece. psfikakis@med.uoa.gr. ·Int J Mol Sci · Pubmed #29954107.

ABSTRACT: Patients with Chronic Inflammatory Rheumatic diseases (CIRD) are at increased risk of cardiovascular disease (CVD), ascribed not only to classical risk factors, but also to the presence of chronic systemic inflammatory response. Αtherosclerosis, the cornerstone of CVD, is known to be accelerated in CIRD; rheumatoid arthritis promotes atheromatosis and associates with preclinical atherosclerosis equivalent to Diabetes Mellitus, which also seems to apply for systemic lupus erythematosus. Data on ankylosing spondylitis and psoriatic arthritis, albeit more limited, also support an increased CV risk in these patients. The association between inflammation and atherosclerosis, has been thoroughly investigated in the last three decades and the role of inflammation in the pathogenesis and progression of atherogenesis has been well established. Endothelial dysfunction, oxidative stress in vascular endothelial cells and macrophage accumulation, toll-like receptor signaling, NLPR-3 formation and subsequent pro-inflammatory cytokine production, such as TNFa, IL-1β, IL-6, and TNF-like cytokine 1A, are few of the mechanisms implicated in the atherogenic process. Moreover, there is evidence that anti-inflammatory biologic drugs, such as anti-TNF and anti-IL1β agents, can decelerate the atherogenic process, thus setting new therapeutic targets for early and effective disease control and suppression of inflammation, in addition to aggressive management of classical CV risk factors.

8 Review Can cardiovascular magnetic resonance prompt early cardiovascular/rheumatic treatment in autoimmune rheumatic diseases? Current practice and future perspectives. 2018

Mavrogeni, Sophie I / Sfikakis, Petros P / Dimitroulas, Theodoros / Koutsogeorgopoulou, Loukia / Katsifis, Gikas / Markousis-Mavrogenis, George / Kolovou, Genovefa / Kitas, George D. ·Onassis Cardiac Surgery Center, 50 Esperou Street, P. Faliro, 175-61, Athens, Greece. soma13@otenet.gr. · First Department of Propaedeutic and Internal Medicine, National and Kapodisstrian University of Athens Medical School, Athens, Greece. · 4th Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. · Pathophysiology Department, National and Kapodisstrian University of Athens Medical School, Athens, Greece. · Naval Hospital, Athens, Greece. · Onassis Cardiac Surgery Center, 50 Esperou Street, P. Faliro, 175-61, Athens, Greece. · Arthritis Research UK Epidemiology Unit, Manchester University, Manchester, UK. ·Rheumatol Int · Pubmed #29516170.

ABSTRACT: Life expectancy in autoimmune rheumatic diseases (ARDs) remains lower compared to the general population, due to various comoborbidities. Cardiovascular disease (CVD) represents the main contributor to premature mortality. Conventional and biologic disease-modifying antirheumatic drugs (DMARDs) have considerably improved long-term outcomes in ARDs not only by suppressing systemic inflammation but also by lowering CVD burden. Regarding atherosclerotic disease prevention, EULAR has recommended tight disease control accompanied by regular assessment of traditional CVD risk factors and lifestyle changes. However, this approach, although rational and evidence-based, does not account for important issues such as myocardial inflammation and the long asymptomatic period that usually proceeds clinical manifestations of CVD disease in ARDs before or after the diagnosis of systemic disease. Cardiovascular magnetic resonance (CMR) can offer reliable, reproducible and operator independent information regarding myocardial inflammation, ischemia and fibrosis. Some studies suggest a role for CMR in the risk stratification of ARDs and demonstrate that oedema/fibrosis visualisation with CMR may have the potential to inform cardiac and rheumatic treatment modification in ARDs with or without abnormal routine cardiac evaluation. In this review, we discuss how CMR findings could influence anti-rheumatic treatment decisions targeting optimal control of both systemic and myocardial inflammation irrespective of clinical manifestations of cardiac disease. CMR can provide a different approach that is very promising for risk stratification and treatment modification; however, further studies are needed before the inclusion of CMR in the routine evaluation and treatment of patients with ARDs.

9 Review Insight into pathogenesis of Sjögren's syndrome: Dissection on autoimmune infiltrates and epithelial cells. 2017

Goules, Andreas V / Kapsogeorgou, Efstathia K / Tzioufas, Athanasios G. ·Department of Pathophysiology & Academic Joint Rheumatology Program, School of Medicine, National University of Athens, Greece; Johns Hopkins University, Department of Medicine, Rheumatology Division, Baltimore, USA. · Department of Pathophysiology & Academic Joint Rheumatology Program, School of Medicine, National University of Athens, Greece. · Department of Pathophysiology & Academic Joint Rheumatology Program, School of Medicine, National University of Athens, Greece. Electronic address: agtzi@med.uoa.gr. ·Clin Immunol · Pubmed #28330683.

ABSTRACT: Sjögren's syndrome (SS) is a chronic autoimmune disease with broad clinical spectrum, extending from benign exocrinopathy to severe systemic disease and lymphoma development. The glandular and extraglandular dysfunction of SS is associated with lymphocytic infiltrates that invade the epithelial structures of affected organs. The in-depth study of autoimmune lesions in the minor salivary glands (MSG), which are the major target-organ of SS responses, revealed that the lymphocytic infiltrates vary in severity and composition among SS-patients, are full-blown at diagnosis and remain unchanged thereafter. Although the pathogenetic pathways underlying SS have not yet elucidated, it is well-established that glandular epithelial cells are central regulators of local autoimmune responses. Moreover, chronic inflammation affects epithelial function and phenotype, which strengthens or weakens their immunoregulatory/secretory function, leading to deterioration of autoimmune phenomena. Herein, the current findings regarding the autoimmune lesions, the role of epithelial cells and their interaction with infiltrating lymphocytic cells are discussed.

10 Review Cadherin-11 as a therapeutic target in chronic, inflammatory rheumatic diseases. 2017

Sfikakis, Petros P / Vlachogiannis, Nikolaos I / Christopoulos, Panagiotis F. ·Rheumatology Unit, First Department of Propaedeutic Internal Medicine and Joint Rheumatology Academic Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: psfikakis@med.uoa.gr. · Rheumatology Unit, First Department of Propaedeutic Internal Medicine and Joint Rheumatology Academic Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. ·Clin Immunol · Pubmed #28115292.

ABSTRACT: Cadherin-11 has been identified as a key regulator of synovial architecture mediating contact between Fibroblast-like Synoviocytes and organization in the lining layer. A central role for cadherin-11 has also been suggested in the formation of the rheumatoid pannus. Therapeutic targeting of cadherin-11 results in amelioration of autoimmune experimental arthritis, as well as of experimental fibrosis. In addition, cadherin-11 expression is upregulated in the synovium of patients with chronic inflammatory arthritis, whereas detection of cadherin-11 mRNA transcripts in the peripheral blood has been associated with more severe disease phenotypes in two prototypic conditions of chronic joint inflammation and fibrosis, namely, rheumatoid arthritis and systemic sclerosis, respectively. Currently, a monoclonal antibody against cadherin-11 is in early phases of clinical trials in patients with rheumatoid arthritis. Herein, we review the current knowledge regarding the potential role of cadherin-11 in pathogenesis, as well as a biomarker and therapeutic target in chronic inflammatory rheumatic diseases.

11 Review Mechanisms and New Strategies for Primary Sjögren's Syndrome. 2017

Mavragani, Clio P. ·Department of Physiology, School of Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece; email: kmauragan@med.uoa.gr. ·Annu Rev Med · Pubmed #28099084.

ABSTRACT: Primary Sjögren's syndrome (SS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, mainly salivary and lacrimal, resulting in oral and ocular dryness, although virtually any organ system can be affected. SS-related systemic manifestations are classified as either related to the presence of periepithelial infiltrates in exocrine and parenchymal organs or resulting from immunocomplex deposition due to B cell hyperactivity with increased risk for B cell lymphoma development. Activation of both innate and adaptive immune pathways contributes to disease pathogenesis, with prominent interferon (IFN) signatures identified in both peripheral blood and affected salivary gland tissues. Recently, LINE-1 genomic repeat elements have been proposed as potential triggers of type I IFN pathway activation in SS through activation of Toll-like receptor-dependent and -independent pathways. In view of the increasingly appreciated variability of SS, elucidation of distinct operating pathways in relation to diverse clinical phenotypes and selection of the optimal therapeutic intervention remain major challenges. Inhibition of cathepsin S molecules, blockade of costimulation through administration of abatacept and inhibitors of B7-related molecules and CD40, blockade of B cell function and B cell survival factors, and disruption of the formation of ectopic germinal centers are considered the main therapeutic targets. Well-controlled multicenter clinical trials are ongoing and data are awaited.

12 Review The autoimmunity-oral microbiome connection. 2017

Nikitakis, N G / Papaioannou, W / Sakkas, L I / Kousvelari, E. ·Department of Oral Pathology and Medicine, Dental School, University of Athens, Athens, Greece. · Dental School, University of Athens, Athens, Greece. · Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece. ·Oral Dis · Pubmed #27717092.

ABSTRACT: To date, there is a major effort in deciphering the role of complex microbial communities, especially the oral and gut microbiomes, in the pathogenesis of various diseases. Increasing evidence indicates a key role for the oral microbiome in autoimmune diseases. In this review article, we discuss links of the oral microbiota to a group of autoimmune diseases, that is, Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), Crohn's disease (CD), and rheumatoid arthritis (RA). We particularly focus on factors that affect the balance between the immune system and the composition of microbiota leading to dysbiosis, loss of tolerance and subsequent autoimmune disease progression and maintenance.

13 Review Impact of non-steroidal anti-inflammatory drugs on cardiovascular risk: Is it the same in osteoarthritis and rheumatoid arthritis? 2017

Bournia, Vasiliki-Kalliopi / Kitas, George / Protogerou, Athanasios D / Sfikakis, Petros P. ·a First Department of Propaedeutic and Internal Medicine and Joined Rheumatology Program , Medical School, National and Kapodistrian University of Athens, Laikon Hospital , Athens , Greece. ·Mod Rheumatol · Pubmed #27659504.

ABSTRACT: Although large-scale population studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of myocardial infarction, this is not confirmed in patients with rheumatoid arthritis (RA). Herein, we review the litterature on the differential effects of NSAIDs on cardiovascular risk in osteoarthritis (OA) versus RA and discuss possible explanations for this discrepancy. To assess a potential additive effect of age in non-RA populations, we compared weighted mean age between RA patients and unselected NSAID users included in cohort and case-control studies that estimate the cardiovascular risk of NSAIDs, assuming that the main indication for NSAID usage in elderly populations is OA. Our hypothesis that advanced age in osteoarthtitis compared to RA patients confounds the effect of NSAIDs on cardiovasular risk was not confirmed. Several other hypotheses that can be proposed to explain this counterintuitive effect of NSAIDs on the cardiovascular risk of RA patients are discussed. We conclude that patients with RA have a lower cardiovascular disease risk associated with the use of NSAIDs, probably due to the nature of their disease per se, until further research indicates differently.

14 Review Primary Sjögren's syndrome: clinical phenotypes, outcome and the development of biomarkers. 2017

Goules, Andreas V / Tzioufas, Athanasios G. ·Department of Pathophysiology, School of Medicine, University of Athens, Mikras Asias Str 75, 115 27, Athens, Greece. · Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. · Department of Pathophysiology, School of Medicine, University of Athens, Mikras Asias Str 75, 115 27, Athens, Greece. agtzi@med.uoa.gr. ·Immunol Res · Pubmed #27444892.

ABSTRACT: Primary Sjögren's syndrome is a complex, autoimmune disease with distinct clinical phenotypes and variable outcomes. The systemic form of the disease is characterized by immune complex-mediated manifestations and is complicated by lymphoma as a result of a polyclonal B cell hyperactivity that is evolving into B cell malignancy. In the past decades, well-established clinical and serological markers have been described in the literature to identify high-risk patients and predict lymphoma development. However, specific biological treatments have proven ineffective to control the disease. Significant research effort has been made to reveal the major underlying biological events in this subgroup and identify biomarkers for early diagnosis, prognosis and response to treatment. In this review, we summarize the current data for the proposed histological, molecular and genetic biomarkers.

15 Review IgG4-related sialadenitis and Sjögren's syndrome. 2017

Fragoulis, G E / Zampeli, E / Moutsopoulos, H M. ·Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK. · Pathophysiology Department, School of Medicine, University of Athens, Athens, Greece. ·Oral Dis · Pubmed #27318181.

ABSTRACT: IgG4-related disease (IgG4-RD) has emerged as a new entity in the last decade. It comprises numerous conditions previously thought to be unrelated. Macroscopically, these diseases cause diffuse organ swelling and formation of pseudotumorous masses. Histopathologically, they are characterized by a lymphoplasmacytic infiltrate with increased IgG4+ plasma cells and storiform fibrosis. Despite rapid progress within the last years, our knowledge on these conditions is still fragmented. To date, more than forty organs have been reported to be included in IgG4-RD, and salivary gland involvement is amongst the most common organs affected [IgG4-related sialadenitis (IgG4-RS)]. Interestingly, IgG4-RS shares commonalities with Sjögren's syndrome (SS), like glandular enlargement, sicca symptoms, arthralgias, hypergammaglobulinemia, hypocomplementemia, and circulating antinuclear antibodies. Nonetheless, they differ in that the incidence of anti-Ro and anti-La reactivity is not frequently found in patients with IgG4-RS, their salivary glands are infiltrated by a large number of IgG4+ plasma cells and IgG4-RS symptoms respond promptly to steroids. The aim of this review was to describe the clinical, serological, histopathological and pathophysiological aspects of IgG4-RS in the context of IgG4-RD and highlight the differences between IgG4-RS and SS.

16 Review Sjögren syndrome. 2016

Brito-Zerón, Pilar / Baldini, Chiara / Bootsma, Hendrika / Bowman, Simon J / Jonsson, Roland / Mariette, Xavier / Sivils, Kathy / Theander, Elke / Tzioufas, Athanasios / Ramos-Casals, Manuel. ·Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA-Sanitas, Barcelona, Spain. · Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Barcelona, Spain. · Department of Autoimmune Diseases, ICMiD, Hospital Clínic, C/Villarroel, 170, 08036 Barcelona, Spain. · Rheumatology Unit, University of Pisa, Pisa, Italy. · Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Rheumatology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. · Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway. · Department of Rheumatology, Haukeland University Hospital, Bergen, Norway. · Université Paris Sud, INSERM, Paris, France. · Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, Paris, France. · Oklahoma Sjögren's syndrome Center of Research Translation, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA. · Department of Rheumatology, Malmö University Hospital, Lund University, Lund, Sweden. · Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece. · Department of Medicine, University of Barcelona, Barcelona, Spain. ·Nat Rev Dis Primers · Pubmed #27383445.

ABSTRACT: Sjögren syndrome (SjS) is a systemic autoimmune disease that primarily affects the exocrine glands (mainly the salivary and lacrimal glands) and results in the severe dryness of mucosal surfaces, principally in the mouth and eyes. This disease predominantly affects middle-aged women, but can also be observed in children, men and the elderly. The clinical presentation of SjS is heterogeneous and can vary from sicca symptoms to systemic disease (characterized by peri-epithelial lymphocytic infiltration of the affected tissue or the deposition of the immune complex) and lymphoma. The mechanism underlying the development of SjS is the destruction of the epithelium of the exocrine glands, as a consequence of abnormal B cell and T cell responses to the autoantigens Ro/SSA and La/SSB, among others. Diagnostic criteria for SjS include the detection of autoantibodies in patient serum and histological analysis of biopsied salivary gland tissue. Therapeutic approaches for SjS include both topical and systemic treatments to manage the sicca and systemic symptoms of disease. SjS is a serious disease with excess mortality, mainly related to the systemic involvement of disease and the development of lymphomas in some patients. Knowledge of SjS has progressed substantially, but this disease is still characterized by sicca symptoms, the systemic involvement of disease, lymphocytic infiltration to exocrine glands, the presence of anti-Ro/SSA and anti-La/SSB autoantibodies and the increased risk of lymphoma in patients with SjS.

17 Review Primary Sjӧgren's syndrome: Clinical phenotypes, outcome and the development of biomarkers. 2016

Goules, Andreas V / Tzioufas, Athanasios G. ·Department of Pathophysiology, School of Medicine, University of Athens, Mikras Asias Str 75, Athens 115 27, Greece. Electronic address: agoules@med.uoa.gr. · Department of Pathophysiology, School of Medicine, University of Athens, Mikras Asias Str 75, Athens 115 27, Greece. Electronic address: agtzi@med.uoa.gr. ·Autoimmun Rev · Pubmed #26970487.

ABSTRACT: Primary Sjӧgren's syndrome (pSS) is a complex autoimmune disease with distinct clinical phenotypes and variable outcomes. The systemic form of the disease is characterized by immune complex mediated manifestations and is complicated by lymphoma as a result of a polyclonal B cell hyperactivity that is evolving into B cell malignancy. In the past decades, well-established clinical and serological markers have been described in the literature to identify high-risk patients and to predict lymphoma development. However, specific biologic treatments have proven ineffective to control the disease. Significant research effort has been made to reveal the major underlying biological events in this subgroup and identify biomarkers for early diagnosis, prognosis and response to treatment. In this review, we summarize the current data for the proposed histological, molecular and genetic biomarkers.

18 Review Early diagnosis of primary Sjögren's syndrome: EULAR-SS task force clinical recommendations. 2016

Brito-Zerón, Pilar / Theander, Elke / Baldini, Chiara / Seror, Raphaèle / Retamozo, Soledad / Quartuccio, Luca / Bootsma, Hendrika / Bowman, Simon J / Dörner, Thomas / Gottenberg, Jacques-Eric / Mariette, Xavier / Bombardieri, Stefano / de Vita, Salvatore / Mandl, Thomas / Ng, Wan-Fai / Kruize, Aike A / Tzioufas, Athanasios / Vitali, Claudio / Buyon, Jill / Izmirly, Peter / Fox, Robert / Ramos-Casals, Manuel / Anonymous7780852. ·a Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, CELLEX-IDIBAPS, Department of Autoimmune Diseases, ICMiD , Hospital Clínic , Barcelona , Spain. · b Department of Rheumatology , Skane University Hospital Malmö, Lund University , Sweden. · c Rheumatology Unit , University of Pisa , Pisa , Italy. · d Department of Rheumatology , Assistance Publique-Hopitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre , Paris , France. · e Department of Rheumatology , Université Paris-Sud, Le Kremlin Bicêtre , Paris , France. · f Hospital Privado Centro Médico , Córdoba , Argentina. · g Clinic of Rheumatology, Department of Medical and Biological Sciences , University Hospital Santa Maria della Misericordia , Udine , Italy. · h Department of Rheumatology and Clinical Immunology , University Medical Center Groningen, University of Groningen , Groningen , the Netherlands. · i Rheumatology Department , University Hospitals Birmingham NHS Foundation Trust , Birmingham , UK. · j Rheumatology Department , Charité, University Hospital , Berlin , Germany. · k Department of Rheumatology , Strasbourg University Hospital, Université de Strasbourg , Strasbourg , France. · l Musculoskeletal Research Group, Institute of Cellular Medicine , Newcastle University , Newcastle upon Tyne , UK. · m Department of Rheumatology and Clinical Immunology , University Medical Center Utrecht , Utrecht , the Netherlands. · n Department of Pathophysiology , School of Medicine, University of Athens , Greece. · o Istituto San Giuseppe , Como and Casa di Cura Lecco , Lecco , Italy. · p Division of Rheumatology, Department of Medicine , New York University School of Medicine , New York , NY , USA. · q Department of Rheumatology , Scripps Memorial Hospital-XiMED , La Jolla , CA , USA. ·Expert Rev Clin Immunol · Pubmed #26691952.

ABSTRACT: Sjögren's syndrome (SjS) is a systemic autoimmune disease that mainly affects the exocrine glands, leading to generalized mucosal dryness. However, primary SjS may initially present with non-sicca (systemic) manifestations. When these features appear before the onset of an overt sicca syndrome, we may talk of an underlying 'occult' SjS. The European League Against Rheumatism (EULAR) has promoted and supported an international collaborative study group (EULAR-SS Task Force) aimed at developing consensual recommendations to provide a homogeneous approach to the patient with primary SjS presenting with systemic involvement. This review summarizes the key factors that should be taken into account in the diagnostic approach in a patient with suspected SjS according to the main clinical patterns of presentation, and is especially focused on organ-specific systemic disease presentations, including a consensus set of recommendations in order to reach an early diagnosis. Close collaboration with the different specialties involved through a comprehensive multidisciplinary approach is essential in SjS patients presenting with systemic involvements.

19 Review Salivaomics for oral diseases biomarkers detection. 2016

Tasoulas, Jason / Patsouris, Efstratios / Giaginis, Constantinos / Theocharis, Stamatios. ·a First Department of Pathology , University of Athens, Medical School , Athens , Greece. · b Department of Food Science and Nutrition , University of the Aegean , Myrina , Lemnos , Greece. ·Expert Rev Mol Diagn · Pubmed #26680995.

ABSTRACT: The variation of saliva composition in different physiological and pathological states is well demonstrated. Several saliva constituents (enzymes, hormones, antibodies, cytokines etc.) are up- or down-regulated in respect to benign, premalignant and malignant conditions in the oral cavity, and several patterns of deregulation are associated with specific disorders. Omics technologies have contributed significantly in the identification of alterations in gene expression, transcription, protein coding and small molecules concentration, in biologic systems. In this aspect, salivaomics integrate these technologies in saliva analysis and represent a novel and holistic approach in oral disease management including diagnosis, prognosis and monitoring. This review summarizes the current research in the discovery of biomarkers and molecular signatures with diagnostic or prognostic utility for oral diseases in saliva. The review also focuses on the emerging issues of the salivaomics technology and saliva diagnostics and the translational potential.

20 Review Is salivary gland ultrasonography a useful tool in Sjögren's syndrome? A systematic review. 2016

Jousse-Joulin, Sandrine / Milic, Vera / Jonsson, Malin V / Plagou, Athena / Theander, Elke / Luciano, Nicoletta / Rachele, Pascale / Baldini, Chiara / Bootsma, Hendrika / Vissink, Arjan / Hocevar, Alojzija / De Vita, Salvatore / Tzioufas, Athanasios G / Alavi, Zarin / Bowman, Simon J / Devauchelle-Pensec, Valerie / Anonymous490852. ·Department of Rheumatology, La Cavale Blanche University Hospital, Department of Rheumatology-ERI 29, Brittany University, Brest, France. · Institute of Rheumatology, School of Medicine, University of Belgrade, Belgrade, Serbia. · Department of Clinical Dentistry, Section for Oral and Maxillofacial Radiology, University of Bergen, Bergen, Norway. · Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece. · Department of Rheumatology, Skåne University Hospital, Malmö, Sweden. · Department of Diagnostic and Interventional Radiology. · Rheumatology Unit, University of Pisa, Pisa, Italy. · Department of Rheumatology and Clinical Immunology. · Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. · Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia. · Rheumatology Clinic, DSMB, Department of Medical and Biological Sciences, University Hospital 'Santa Maria della Misericordia', Udine, Italy. · INSERM, CIC 1412, Brest Medical University Hospital, Brest, France and. · New Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham B15 2WB, UK. · Department of Rheumatology, La Cavale Blanche University Hospital, Department of Rheumatology-ERI 29, Brittany University, Brest, France, valerie.devauchelle-pensec@chu-brest.fr. ·Rheumatology (Oxford) · Pubmed #26667216.

ABSTRACT: OBJECTIVE: Ultrasonography (US) is a sensitive tool in the diagnosis of major salivary gland abnormalities in primary Sjögren's syndrome (pSS). The aim of this systematic review was to assess the metric properties of this technique. METHODS: PUBMED and EMBASE databases were searched. All publications between January 1988 and January 2013 were considered. Data were extracted from the articles meeting the inclusion criteria according to US definition of salivary gland scoring system and metric properties studied. The type and number of glands tested, study design and metric properties according to OMERACT filter (truth, discrimination, feasibility) were assessed. RESULTS: Of 167 publications identified initially with PUBMED and EMBASE, 31 met the inclusion criteria. The number of pSS patients varied among the studies from 16 to 140. The diagnosis of pSS was in line in most of the cases with the American-European Consensus Group (AECG) classification criteria for Sjögren's syndrome. The US examination was performed in suspected pSS only in studies in which the sensitivity ranged from 45.8 to 91.6% and specificity from 73 to 98.1%. There was heterogeneity in regard to the definition of US in B-mode and few studies used US in colour Doppler. Few studies reported reliability of US and sensitivity to change in pSS. CONCLUSION: US is a valuable tool for detecting salivary gland abnormalities in pSS. Its reliability has been poorly investigated and there is considerable variation in the definition of US abnormalities. Further studies are required to validate and standardize the US definition of salivary gland in pSS.

21 Review Immunotherapies for Neurological Manifestations in the Context of Systemic Autoimmunity. 2016

Kampylafka, Eleni I / Alexopoulos, Harry / Dalakas, Marinos C / Tzioufas, Athanasios G. ·Department of Pathophysiology, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, 11527, Greece. · Department of Pathophysiology, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, 11527, Greece. agtzi@med.uoa.gr. ·Neurotherapeutics · Pubmed #26510559.

ABSTRACT: Neurological involvement is relatively common in the majority of systemic autoimmune diseases and may lead to severe morbidity and mortality, if not promptly treated. Treatment options vary greatly, depending on the underlying systemic pathophysiology and the associated neurological symptoms. Selecting the appropriate therapeutic scheme is further complicated by the lack of definite therapeutic guidelines, the necessity to differentiate primary neurological syndromes from those related to the underlying systemic disease, and to sort out adverse neurological manifestations caused by immunosuppressants or the biological agents used to treat the primary disease. Immunotherapy is a sine qua non for treating most, if not all, neurological conditions presenting in the context of systemic autoimmunity. Specific agents include classical immune modulators such as corticosteroids, cyclophosphamide, intravenous immunoglobulin, and plasma exchange, as well as numerous biological therapies, for example anti-tumor necrosis factor agents and monoclonal antibodies that target various immune pathways such as B cells, cytokines, and co-stimulatory molecules. However, experience regarding the use of these agents in neurological complications of systemic diseases is mainly empirical or based on small uncontrolled studies and case series. The aim of this review is to present the state-of-the-art therapies applied in various neurological manifestations encountered in the context of systemic autoimmune diseases; evaluate all treatment options on the basis of existing guidelines; and compliment these data with our personal experience derived from a large number of patients.

22 Review Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. 2016

Smolen, Josef S / Breedveld, Ferdinand C / Burmester, Gerd R / Bykerk, Vivian / Dougados, Maxime / Emery, Paul / Kvien, Tore K / Navarro-Compán, M Victoria / Oliver, Susan / Schoels, Monika / Scholte-Voshaar, Marieke / Stamm, Tanja / Stoffer, Michaela / Takeuchi, Tsutomu / Aletaha, Daniel / Andreu, Jose Louis / Aringer, Martin / Bergman, Martin / Betteridge, Neil / Bijlsma, Hans / Burkhardt, Harald / Cardiel, Mario / Combe, Bernard / Durez, Patrick / Fonseca, Joao Eurico / Gibofsky, Alan / Gomez-Reino, Juan J / Graninger, Winfried / Hannonen, Pekka / Haraoui, Boulos / Kouloumas, Marios / Landewe, Robert / Martin-Mola, Emilio / Nash, Peter / Ostergaard, Mikkel / Östör, Andrew / Richards, Pam / Sokka-Isler, Tuulikki / Thorne, Carter / Tzioufas, Athanasios G / van Vollenhoven, Ronald / de Wit, Martinus / van der Heijde, Desirée. ·Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria. · Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. · Department of Rheumatology, Clinical Immunology Free University and Humboldt University, Charité-University Medicine, Berlin, Germany. · Division of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, Cornell University, New York, USA. · Department of Rheumatology B, Cochin Hospital, René Descartes University, Paris, France. · Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Susan Oliver Associates, North Devon, UK. · 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria. · EULAR Standing Committee of People with Arthritis/Rheumatism in Europe (PARE), Zurich, Switzerland. · Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · Division of Rheumatology, Department of internal Medicine, Keio University School of Medicine, Tokyo, Japan. · Rheumatology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain. · Department of Medicine III, University Medical Center TU Dresden, Dresden, Germany. · Drexel University College of Medicine, Philadelphia, Pennsylvania, USA. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, and VU University Medical Center, Amsterdam, The Netherlands. · Division of Rheumatology, Department of Medicine, Johann-Wolfgang-Goethe University Frankfurt, German. · Centro de Investigación Clínica de Morelia, Morelia, Michoacán, Mexico. · Service d'Immuno-Rhumatologie, Montpellier University, Lapeyronie Hospital, Montpellier, France. · Pôle de Recherche en Rhumatologie, Institut de Recherche Experimentale et Clinique, Université Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels, Belgium. · Rheumatology Research Unit, Instituto de de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal Rheumatology Department, Lisbon Academic Medical Centre, Lisbon, Portugal. · Weill Medical College, Cornell University Hospital for Special Surgery, New York, USA. · Rheumatology Unit, Santiago University Clinical Hospital, Santiago de Compostela, Spain. · Division of Rheumatology, Medical University of Graz, Graz, Austria. · Department of Medicine, Central Hospital, Jyväskylä, Finland. · Institut de Rhumatologie de Montréal, Quebec, Canada. · Academic Medical Center, University of Amsterdam, Amsterdam, and Atrium Medical Center, Heerlen, The Netherlands. · University Hospital La Paz, Madrid, Spain. · University of Queensland, Brisbane, Queensland, Australia. · Department of Clinical Medicine, Faculty of Health Sciences, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet and Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark. · Rheumatology Clinical Research Unit, School of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge University Hospitals, NHS Foundation Trust, Cambridge, UK. · Department of Rheumatology, Central Hospital, Jyväskylä, Finland. · Division of Rheumatology, Southlake Regional Health Centre, Newarket, Ontario, Canada. · Department of Pathophysiology, School of Medicine, University of Athens, Greece. · Rheumatology Clinic, Karolinska University Hospital, Stockholm, Sweden. · Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK. ·Ann Rheum Dis · Pubmed #25969430.

ABSTRACT: BACKGROUND: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. OBJECTIVE: To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. METHODS: A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. RESULTS: The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1-3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10). CONCLUSIONS: The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA.

23 Review Contribution of Genetic Factors to Sjögren's Syndrome and Sjögren's Syndrome Related Lymphomagenesis. 2015

Nezos, Adrianos / Mavragani, Clio P. ·Department of Physiology, Medical School, University of Athens, Mikras Asias 75, 11527 Athens, Greece. ·J Immunol Res · Pubmed #26550578.

ABSTRACT: We aimed to summarize the current evidence related to the contributory role of genetic factors in the pathogenesis of Sjögren's syndrome (SS) and SS-related lymphoma. Genes within the major histocompatibility complex (MHC) locus previously considered conferring increased susceptibility to SS development have been also revealed as important contributors in recent genome wide association studies. Moreover, genetic variations outside the MHC locus involving genes in type I interferon pathway, NF-κB signaling, B- and T-cell function and methylation processes have been shown to be associated with both SS and SS-related lymphoma development. Appreciating the functional implications of SS-related genetic variants could provide further insights into our understanding of SS heterogeneity, allowing the design of tailored therapeutic interventions.

24 Review Treatment of rheumatoid arthritis: Unraveling the conundrum. 2015

Zampeli, Evangelia / Vlachoyiannopoulos, Panayiotis G / Tzioufas, Athanasios G. ·Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece. · Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece. Electronic address: agtzi@med.uoa.gr. ·J Autoimmun · Pubmed #26515757.

ABSTRACT: Rheumatoid arthritis (RA) is a heterogeneous disease with a complex and yet not fully understood pathophysiology, where numerous different cell-types contribute to a destructive process of the joints. This complexity results into a considerable interpatient variability in clinical course and severity, which may additionally involve genetics and/or environmental factors. After three decades of focused efforts scientists have now achieved to apply in clinical practice, for patients with RA, the "treat to target" approach with initiation of aggressive therapy soon after diagnosis and escalation of the therapy in pursuit of clinical remission. In addition to the conventional synthetic disease modifying anti-rheumatic drugs, biologics have greatly improved the management of RA, demonstrating efficacy and safety in alleviating symptoms, inhibiting bone erosion, and preventing loss of function. Nonetheless, despite the plethora of therapeutic options and their combinations, unmet therapeutic needs in RA remain, as current therapies sometimes fail or produce only partial responses and/or develop unwanted side-effects. Unfortunately the mechanisms of 'nonresponse' remain unknown and most probable lie in the unrevealed heterogeneity of the RA pathophysiology. In this review, through the effort of unraveling the complex pathophysiological pathways, we will depict drugs used throughout the years for the treatment of RA, the current and future biological therapies and their molecular or cellular targets and finally will suggest therapeutic algorithms for RA management. With multiple biologic options, there is still a need for strong predictive biomarkers to determine which drug is most likely to be effective, safe, and durable in a given individual. The fact that available biologics are not effective in all patients attests to the heterogeneity of RA, yet over the long term, as research and treatment become more aggressive, efficacy, toxicity, and costs must be balanced within the therapeutic equation to enhance the quality of life in patients with RA.

25 Review An update of neurological manifestations of vasculitides and connective tissue diseases: a literature review. 2015

Bougea, Anastasia / Anagnostou, Evangelos / Spandideas, Nikolaos / Triantafyllou, Nikolaos / Kararizou, Evangelia. ·University of Athens Medical School, Athens, Greece. ·Einstein (Sao Paulo) · Pubmed #26313435.

ABSTRACT: Vasculitides comprise a heterogeneous group of autoimmune disorders, occurring as primary or secondary to a broad variety of systemic infectious, malignant or connective tissue diseases. The latter occur more often but their pathogenic mechanisms have not been fully established. Frequent and varied central and peripheral nervous system complications occur in vasculitides and connective tissue diseases. In many cases, the neurological disorders have an atypical clinical course or even an early onset, and the healthcare professionals should be aware of them. The purpose of this brief review was to give an update of the main neurological disorders of common vasculitis and connective tissue diseases, aiming at accurate diagnosis and management, with an emphasis on pathophysiologic mechanisms.

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