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Rheumatoid Arthritis: HELP
Articles from University of Athens
Based on 180 articles published since 2009
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These are the 180 published articles about Arthritis, Rheumatoid that originated from University of Athens during 2009-2019.
 
+ 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 / Anonymous451201. ·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 Variation in primary Sjögren's syndrome care among European countries. 2019

Seghieri, Chiara / Lupi, Enrico / Exarchos, Themis P / Ferro, Francesco / Tzioufas, Athanasios G / Baldini, Chiara. ·Institute of Management and Department EMbeDS, Scuola Superiore Sant'Anna, Pisa, Italy. chiara.seghieri@santannapisa.it. · Institute of Management and Department EMbeDS, Scuola Superiore Sant'Anna, Pisa, Italy. · Unit of Medical Technology and IntelligentInformation Systems, University of Ioannina, Greece. · Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy. · Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Greece. ·Clin Exp Rheumatol · Pubmed #31464679.

ABSTRACT: -- No abstract --

3 Editorial The necessity of novel biomarkers in primary Sjögren's syndrome. 2019

Tzioufas, Athanasios G / Goules, Andreas V. ·Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Greece. agtzi@med.uoa.gr. · Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Greece. ·Clin Exp Rheumatol · Pubmed #31464672.

ABSTRACT: -- No abstract --

4 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 --

5 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 --

6 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 --

7 Review One year in review 2019: Sjögren's syndrome. 2019

Cafaro, Giacomo / Croia, Cristina / Argyropoulou, Ourania D / Leone, Maria Comasia / Orlandi, Martina / Finamore, Francesco / Cecchettini, Antonella / Ferro, Francesco / Baldini, Chiara / Bartoloni, Elena. ·Rheumatology Unit, Department of Medicine, University of Perugia, Italy. · Immuno-Allergology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy. · Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Greece. · Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Florence, Italy. · Laboratorio Proteomica, CNR Pisa, Italy. · Department of Clinical and Experimental Medicine, University of Pisa, Italy. · Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy. · Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy. chiara.baldini74@gmail.com. ·Clin Exp Rheumatol · Pubmed #31464675.

ABSTRACT: Primary Sjögren's syndrome (pSS) is a complex and heterogeneous disorder characterised by a wide spectrum of glandular and extra-glandular features. Novel insights into disease pathogenesis and the discovery of novel biomarkers are allowing us to characterise the disease not only phenotypically on the basis of clinical presentation, but also on the basis of the endotype. Ultimately, a better stratification of patients may pave new avenues for novel targeted therapies, opening new possibilities for the application of personalised medicine in pSS.

8 Review Sjögren's syndrome towards precision medicine: the challenge of harmonisation and integration of cohorts. 2019

Goules, Andreas V / Exarchos, Themis P / Pezoulas, Vasilis C / Kourou, Konstadina D / Venetsanopoulou, Aliki I / De Vita, Salvatore / Fotiadis, Dimitrios I / Tzioufas, Athanasios G. ·Pathophysiology Department, Athens School of Medicine, National and Kapodistrian University of Athens, Greece. · Unit of Medical Technology and Intelligent Information Systems, University of Ioannina, Greece. · Rheumatology Clinic, DSMB, AOU Santa Maria della Misericordia, University of Udine, Italy. · Pathophysiology Department, Athens School of Medicine, National and Kapodistrian University of Athens, Greece. agtzi@med.uoa.gr. ·Clin Exp Rheumatol · Pubmed #31464663.

ABSTRACT: Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease with diverse clinical picture and outcome. The disease affects primarily middle-aged females and involves the exocrine glands leading to dry mouth and eyes. When the disease extends beyond the exocrine glands (systemic form), certain extraglandular manifestations involving liver, kidney, lungs, peripheral nervous system and the skin may occur. Primary SS is considered the crossroad between autoimmunity and lymphoproliferation, since approximately 5% of patients develop NHL associated lymphomas. As with every chronic disease with complex aetiopathogenesis and clinical heterogeneity, pSS has certain unmet needs that have to be addressed: a) classification and stratification of patients; b) understanding the distinct pathogenetic mechanisms and clinical phenotypes; c) defining and interpreting the real needs of patients regarding the contemporary diagnostic and therapeutic approaches; d) physician and patients' training regarding the wide spectrum of the disease; e) creating common policies across European countries to evaluate and manage SS patients. To achieve these goals, an intense effort is being currently undertaken by the HarmonicSS consortium in order to harmonise and integrate the largest European cohorts of pSS patients. In this review, we present an overview of our perception and vision, as well as new issues arising from this project such as harmonisation protocols and procedures, data sharing principles and various ethical and legal issues originating from these approaches.

9 Review Type I interferon signature in Sjögren's syndrome: pathophysiological and clinical implications. 2019

Marketos, Nikolaos / Cinoku, Ilir / Rapti, Anna / Mavragani, Clio P. ·Department of Physiology, National and Kapodistrian University of Athens, Greece. · Departments of Physiology and Pathophysiology, Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Greece. kmauragan@med.uoa.gr. ·Clin Exp Rheumatol · Pubmed #31376268.

ABSTRACT: Type I interferons (IFN) have long been recognised as mediators of innate immune defense mechanisms against viral threats. Robust evidence over the last 15 years revealed their significant role in the pathogenesis of systemic autoimmune diseases, including systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). Despite the progress, methods of detection, initial triggers, biological functions and clinical associations in the setting of autoimmunity remain to be fully clarified. As therapeutic options for SS are currently limited, neutralising specific targets of the type I IFN pathway seems a promising option. In this review we summarise the current evidence regarding the role of type I IFN in SS.

10 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.

11 Review Bone erosions in rheumatoid arthritis: recent developments in pathogenesis and therapeutic implications. 2018

Panagopoulos, Panagiotis K / Lambrou, George I. ·Graduate Programme "Metabolic Bone Diseases", National and Kapodistrian University of Athens, Medical School. ·J Musculoskelet Neuronal Interact · Pubmed #30179207.

ABSTRACT: Bone erosions develop early in the course of rheumatoid arthritis (RA) and deteriorate progressively, causing joint damage and resulting in impaired functional capacity of patients. During the last years, considerable number of studies has increased our understanding of the pathogenetic mechanisms mediating the development of bone erosions in RA. Increased production of RANKL and other cytokines, dysregulation of innate immune mechanisms, autoantibodies specific to RA and alterations of microRNA expression stimulate differentiation and function of osteoclasts, which are responsible for the development of bone erosions. Besides, increased levels of cytokines, overproduction of antagonists of the canonical Wnt signaling pathway and deficient production of bone morphogenetic proteins result in impaired osteoblast differentiation and function, undermining the capacity of bone erosions to repair. Disease-modifying antirheumatic drugs, synthetic or biological, currently used in the treatment of RA, can halt the progression of bone erosions and may even lead to partial repair, although complete repair is unattainable. Targeting pathogenetic mechanisms participating in the erosive process may add to the therapeutic effect of DMARDs and help in the prevention or repair of bone erosions. However, more studies are still needed to confirm whether such therapeutic strategies are effective.

12 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.

13 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.

14 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.

15 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.

16 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.

17 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.

18 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.

19 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.

20 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.

21 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.

22 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.

23 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.

24 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.

25 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.

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