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Haralampos M Moutsopoulos - One of the best experts on this subject based on the ideXlab platform.
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Sjögren's syndrome: Old and new therapeutic targets
Journal of autoimmunity, 2019Co-Authors: Clio P. Mavragani, Haralampos M MoutsopoulosAbstract:Sjogren's syndrome (SS) is a prototype autoimmune disease characterized by oral and ocular Mucosal Dryness following chronic inflammation of salivary and lachrymal glands, respectively. Profound B cell hyperactivity along with systemic manifestations including fatigue, musculoskeletal complaints, features related to hepatic, pulmonary, renal and nervous system involvement, as well as lymphoma development can be also present. Despite that activation of both innate and adaptive immune pathways has been long well documented in SS pathogenesis, systemic immunosuppression in SS, in contrast to other autoimmune diseases, has been largely inefficacious. Biological agents previously implemented in successful therapeutic outcomes in rheumatoid arthritis (RA), such as anti-TNF agents, anakinra, tocilizumab and rituximab failed to reach primary outcomes in randomized double-blind controlled trials in the context of SS. Abatacept and belimumab, already licensed for the treatment of RA and lupus respectively, as well combination regimens of both rituximab and belimumab hold some promise in alleviation of SS-specific complaints, but data from large controlled trials are awaited. Recent advances in dissecting the molecular pathways underlying SS pathogenesis led to an expanding number of novel biological compounds directed towards type I interferon system, antigen presentation, costimulatory pathways, B and T cell activation, as well as germinal center formation. While targeting of cathepsin-S (Petesicatib), inducible costimulator of T cells ligand (prezalumab), and lymphotoxin beta receptor (baminercept) failed to fulfil the primary outcome measures, preliminary results from two randomized placebo controlled trials on CD40 blockade (Iscalimab) and B-cell activating factor receptor (Ianalumab) inhibition resulted in significant reduction of SS disease activity, with a favorable so far safety profile. Results from administration of other kinase inhibitors, a transmembrane activator and calcium-modulator and cytophilin ligand interactor TACI fusion protein (RC18), as well as low dose recombinant interleukin-2 to expand T-regulatory cells are currently awaited.
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Primary versus Secondary Sjögren Syndrome: Is It Time To Reconsider These Terms?
The Journal of rheumatology, 2019Co-Authors: Clio P. Mavragani, Haralampos M MoutsopoulosAbstract:Classification of systemic autoimmune diseases on the basis of clinical, serological, and genetic characteristics has long been considered a necessary approach to determine disease prognosis and institute appropriate therapeutic strategies1. Has this, however, truly been pursued by the scientific community? Probably not, because similar disease-modifying agents and several immunosuppressants are implemented as baseline therapy for combating arthritis, pleurisy, or nephritis, irrespective of the character of the underlying disease. Despite our better understanding of molecular patho-biology, which eventually led to development of targeted therapies, seropositive and seronegative arthritis are still similarly treated with tumor necrosis factor inhibitors, while certain vasculitic syndromes are managed with B cell depletion therapy in the same way as rheumatoid arthritis (RA). The responses, even to those new therapies, are not uniform because these syndromes are highly polymorphic in both clinical phenotypes and underlying pathogenetic pathways. A prototype autoimmune disorder characterized by a wide spectrum of clinical, serological, and genetic features is Sjogren syndrome (SS). It may extend from sicca symptoms and complications of Mucosal Dryness as a result of exocrine gland involvement, to a systemic disease or to malignant B cell lymphoproliferation in about one-fourth and one-tenth of patients, respectively. Nevertheless, sicca manifestations may also occur in several other systemic autoimmune disorders at variable frequencies ranging from 8.3% … Address correspondence to Dr. C.P. Mavaragani, Department of Physiology, 75 Mikras Asias St., 11527 Athens, Greece. E-mail: kmauragan{at}med.uoa.gr
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Classification criteria of Sjogren's syndrome.
Journal of autoimmunity, 2014Co-Authors: Andreas V Goules, Athanasios G Tzioufas, Haralampos M MoutsopoulosAbstract:Sjogren's syndrome (SS) is a chronic, systemic autoimmune disease that affects typically the exocrine glands causing Mucosal Dryness. Dry eyes and mouth are considered by far the most common and early symptoms of the disease but systemic complications may also occur. In 1993, the preliminary European criteria were proposed and widely accepted, consisting of both subjective and objective criteria. Almost ten years later, these classification criteria were revised by introducing more stringent rules and precise diagnostic procedures leading to the currently used American-European Consensus Group (AECG) criteria. The AECG criteria have been largely employed to conduct epidemiologic and clinical studies of patients with SS and proved to be more specific compared to the preliminary European criteria. The recent American College of Rheumatology/Sjogren's International Collaborative Clinical Alliance (ACR/SICCA) criteria that are based exclusively on objective tests, the stringency of the AECG criteria and the potential therapeutic use of biologic agents in SS clearly set the need for new classification criteria. Whether the new diagnostic approach will further encompass subclinical and early forms of the disease remains to be addressed by the scientific community.
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Sjögren's Syndrome and the Lung
Pulmonary involvement in systemic autoimmune diseases, 2007Co-Authors: Spyros Papiris, Haralampos M MoutsopoulosAbstract:Publisher Summary This chapter explains Sjogren's syndrome and the lung. Sjogren's syndrome, an autoimmune epithelitis, is a chronic, slowly progressive inflammatory autoimmune disease, characterized by lymphocytic infiltration of the exocrine glands and epithelia in multiple sites, leading to diminished or absent glandular secretions and to a more or less generalized, Mucosal Dryness. Sjogren's syndrome presents with a wide spectrum: from lacrimal and salivary exocrinopathy to systemic disease (lungs, liver, kidneys, and other organs or tissues), and, later in the illness and in a small number of patients (≈5%), an associated B-cell lymphoid malignancy. The chapter illustrates that Sjogren's syndrome can occur alone (primary Sjogren's syndrome) or in association with almost all of the other rheumatic autoimmune disorders (secondary Sjogren's syndrome). The co-existing rheumatic disease may be already present at the time of diagnosis of Sjogren's syndrome, or may later become apparent.
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Central nervous system involvement in Sjögren’s syndrome
Annals of the rheumatic diseases, 2004Co-Authors: Fotini C. Soliotis, Clio P. Mavragani, Haralampos M MoutsopoulosAbstract:Still an unresolved issue—multicentre studies are needed Sjogren’s syndrome (SS) is a relatively common autoimmune disorder, affecting 2–3% of the adult population. It is characterised by lymphocytic infiltration and destruction of the exocrine glands. The salivary and lachrymal glands are primarily affected, leading to a dry mouth and dry eyes, the hallmark of the disease. Other exocrine glands, which may be affected, include those of the pancreas, bronchial tree, and gastrointestinal tract. SS may occur alone (primary) or in association with other connective tissue diseases (secondary). The spectrum of clinical manifestations of SS is wide, ranging from Mucosal Dryness, directly related to exocrine dysfunction, to more systemic complaints, affecting mainly the musculoskeletal, pulmonary, renal, and vascular systems.1 Peripheral nervous system disease, manifested commonly as peripheral sensory neuropathy or more rarely as mononeuritis multiplex, is a well established feature of the disease, occurring in approximately a quarter of patients.2 However, involvement of the central nervous system (CNS) in patients with SS is a matter of serious controversy between different research groups, with a prevalence ranging from “undetectable” to “quite common”. This discrepancy was previously attributed possibly to differences in the diagnostic criteria, selection of populations, special interests of different teams of investigators, or referral bias.3,4 The prevalence of CNS disease in SS is a controversial topic. Tables 1 and 2 list the prevalence of CNS manifestations in patients with SS reported since 1985. The numbers quoted in publications range between 0 and 100%.2,5–21 View this table: Table 1 CNS involvement in SS: reported prevalence View this table: Table 2 Psychiatric involvement in SS: reported prevalence Why is there is such a huge variability in the reported prevalence of CNS disease in SS? Firstly, there is no consensus on the definition of CNS involvement. Some authors include psychiatric disease, but some do not. Also there …
Jacques-eric Gottenberg - One of the best experts on this subject based on the ideXlab platform.
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Early diagnosis of primary Sjögren’s syndrome: EULAR-SS task force clinical recommendations
Expert review of clinical immunology, 2015Co-Authors: Pilar Brito-zerón, Simon J. Bowman, Elke Theander, Chiara Baldini, Raphaèle Seror, Soledad Retamozo, Luca Quartuccio, Hendrika Bootsma, Thomas Dörner, Jacques-eric GottenbergAbstract:Sjogren'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.
Simon J. Bowman - One of the best experts on this subject based on the ideXlab platform.
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Early diagnosis of primary Sjögren’s syndrome: EULAR-SS task force clinical recommendations
Expert review of clinical immunology, 2015Co-Authors: Pilar Brito-zerón, Simon J. Bowman, Elke Theander, Chiara Baldini, Raphaèle Seror, Soledad Retamozo, Luca Quartuccio, Hendrika Bootsma, Thomas Dörner, Jacques-eric GottenbergAbstract:Sjogren'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.
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Patient-reported outcomes including fatigue in primary Sjögren's syndrome.
Rheumatic diseases clinics of North America, 2008Co-Authors: Simon J. BowmanAbstract:The hallmark of Sjogren's syndrome is focal lymphocytic infiltration of exocrine glands leading to Mucosal Dryness, particularly of the eyes and mouth. In addition, approximately 70% of patients report fatigue as a particularly prominent and disabling feature associated with reduced health-related quality of life. Other key patient-reported extraglandular symptoms include arthralgia, myalgia, and Raynaud's phenomenon. This article reviews these patient-reported features, their relationships with objective assessment of the disease, potential therapies for these symptoms, and how measurements of these symptoms are relevant to outcome assessment in clinical therapeutic trials.
Pilar Brito-zerón - One of the best experts on this subject based on the ideXlab platform.
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Early diagnosis of primary Sjögren’s syndrome: EULAR-SS task force clinical recommendations
Expert review of clinical immunology, 2015Co-Authors: Pilar Brito-zerón, Simon J. Bowman, Elke Theander, Chiara Baldini, Raphaèle Seror, Soledad Retamozo, Luca Quartuccio, Hendrika Bootsma, Thomas Dörner, Jacques-eric GottenbergAbstract:Sjogren'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.
Alessia Alunno - One of the best experts on this subject based on the ideXlab platform.
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The Serological Status Affects the Prognostic Role of Salivary Gland Histology in Primary Sjögren Syndrome.
The Journal of rheumatology, 2020Co-Authors: Francesco Carubbi, Alessia AlunnoAbstract:We read with interest the article by Sharma, et al that evaluated a cohort of patients with symptoms of Mucosal Dryness undergoing diagnostic workup for the suspicion of primary Sjogren syndrome (pSS)1. The assessment also included a minor salivary gland (MSG) biopsy and patients were classified as pSS if fulfilling the histological [focus score (FS) ≥ 1], serological (anti-Ro based on the American College of Rheumatology/European League Against Rheumatism set or either anti-Ro or anti-La based on the American-European Consensus Group set), or both criteria2,3. Among the 229 subjects classified as having pSS, the authors observed a FS = 0 in 51 subjects (22%), between 0 and 1 in 11 subjects (5%), and ≥ 1 in 167 subjects (73%). According to this, patients were divided in 3 groups, and clinical and serological features were compared. In the FS ≥ 1 group, only patients with anti-Ro … Address correspondence to Dr. F. Carubbi, MD, PhD, Rheumatology Unit, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L’Aquila, L’Aquila, Italy; Department of Medicine, ASL1 Avezzano-Sulmona-L’Aquila, L’Aquila, Italy. Email: francescocarubbi{at}libero.it.
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Discrepancy between subjective symptoms, objective measures and disease activity indexes: the lesson of primary Sjögren's syndrome.
Clinical and experimental rheumatology, 2018Co-Authors: Alessia Alunno, Maria Comasia Leone, Giacomo Cafaro, Valentina Valentini, Elisa Marcucci, Elena Bartoloni, Giuliana Maria Concetta La Paglia, Eleonora Valentini, Angelo Francesco Bonifacio, Filippo LuccioliAbstract:Mucosal Dryness is a key clinical feature in primary Sjogren's syndrome (pSS) and its assessment relies on both objective measurement of residual secretion and subjective symptoms reported by patients. However, while the objective assessment and grading of glandular dysfunction can be easily performed, the spectrum of clinical symptoms encompassed by the terms 'dry eye' and 'dry mouth' is wide and heterogeneous. Therefore, patient reported outcomes (PROs) for Dryness in pSS poorly correlate with the amount of glandular secretion. In addition, subjective Dryness is not correlated with the severity of systemic disease and severely affects the patient quality of life even in presence of active extraglandular manifestations. The purpose of this review article is to provide an overview of glandular dysfunction in pSS as well as the impact of discrepancy between objective assessment, subjective symptom and extraglandular disease activity on disease management.
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Lymphoma and Lymphomagenesis in Primary Sjögren's Syndrome.
Frontiers in medicine, 2018Co-Authors: Alessia Alunno, Maria Comasia Leone, Roberto Gerli, Roberto Giacomelli, Francesco CarubbiAbstract:Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease mainly affecting exocrine glands and leading to impaired secretory function. The clinical picture is dominated by signs and symptoms of Mucosal Dryness and the course of the disease is mild and indolent in the majority of cases. However, a subgroup of patients can also experience extraglandular manifestations that worsen the disease prognosis. pSS patients are consistently found to have a higher risk of developing non-Hodgkin lymphoma (NHL) compared with patients with other autimmune disorders and to the general population. NHL is the most severe comorbidity that can occur in pSS, therefore recent research has aimed to identify reliable clinical, serological, and histological biomarkers able to predict NHL development in these subjects. This review article encompasses the body of evidence published so far in this field highlighting the challenges and pitfalls of different biomarkers within clinical practice. We also provide an overview of epidemiological data, diagnostic procedures, and evidence-based treatment strategies for NHL in pSS.
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Lymphoma and Lymphomagenesis in Primary Sjögren’s Syndrome
Frontiers Media S.A., 2018Co-Authors: Alessia Alunno, Maria Comasia Leone, Roberto Gerli, Roberto Giacomelli, Francesco CarubbiAbstract:Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease mainly affecting exocrine glands and leading to impaired secretory function. The clinical picture is dominated by signs and symptoms of Mucosal Dryness and the course of the disease is mild and indolent in the majority of cases. However, a subgroup of patients can also experience extraglandular manifestations that worsen the disease prognosis. pSS patients are consistently found to have a higher risk of developing non-Hodgkin lymphoma (NHL) compared with patients with other autimmune disorders and to the general population. NHL is the most severe comorbidity that can occur in pSS, therefore recent research has aimed to identify reliable clinical, serological, and histological biomarkers able to predict NHL development in these subjects. This review article encompasses the body of evidence published so far in this field highlighting the challenges and pitfalls of different biomarkers within clinical practice. We also provide an overview of epidemiological data, diagnostic procedures, and evidence-based treatment strategies for NHL in pSS
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the clinical spectrum of primary sjogren s syndrome beyond exocrine glands
Reumatismo, 2017Co-Authors: Maria Comasia Leone, Alessia Alunno, Giacomo Cafaro, Valentina Valentini, Elisa Marcucci, Elena Bartoloni, Roberto GerliAbstract:Although primary Sjogren's syndrome (pSS) is a mild indolent chronic disease mainly characterized by Mucosal Dryness in the majority of cases, a consistent subgroup of patients display extra-glandular manifestations. Virtually any organs and systems can be affected, leading to a more serious disease prognosis. Therefore, the prompt identification of patients at higher risk of extra-glandular manifestations is necessary to start a thorough follow up and an aggressive treatment. The aim of this review article is to provide an overview of epidemiological, clinical and serological features of extra-glandular manifestations in pSS as well as current knowledge about putative biomarkers useful in clinical practice.