Pathogenesis of Sjögren's syndrome (original) (raw)
Related papers
Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy
Journal of Clinical Medicine
Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune rheumatic disease characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands, whereby sicca syndrome and/or systemic manifestations are the clinical hallmarks, associated with a particular autoantibody profile. pSS is the most frequent connective tissue disease after rheumatoid arthritis, affecting 0.3–3% of the population. Women are more prone to develop pSS than men, with a sex ratio of 9:1. Considered in the past as innocent collateral passive victims of autoimmunity, the epithelial cells of the salivary glands are now known to play an active role in the pathogenesis of the disease. The aetiology of the “autoimmune epithelitis” still remains unknown, but certainly involves genetic, environmental and hormonal factors. Later during the disease evolution, the subsequent chronic activation of B cells can lead to the development of systemic manifestations or non-Hodgkin’s lymphoma. The aim of th...
Update on Pathogenesis of Sjögren's syndrome
Current rheumatology reviews, 2016
Sjögren's syndrome is a common autoimmune disease that presents with sicca symptoms and extraglandular features. Sjögren's syndrome is presumably as common as RA; yet it is poorly understood, underdiagnosed and undertreated. From the usual identity as an autoimmune exocrinopathy to its most recent designate as an autoimmune epithelitis - the journey of SS is complex. We herein review some of the most important milestones that have shed light on different aspects of pathogenesis of this enigmatic disease. This includes role of salivary gland epithelial cells, and their interaction with cells of innate and adaptive immune system. Non-immune factors acting in concert or in parallel with immune factors may also be important. The risk genes identified so far have only weak association, nevertheless advances in genetics have enhanced understanding of disease mechanisms .Role of epigenetic and environmental factors are also being explored. SS has also some unique features such as c...
Proceedings of the National Academy of Sciences, 1998
The NOD (nonobese diabetic) mouse has been studied as an animal model for autoimmune insulindependent diabetes and Sjögren's syndrome. NOD.Ig null mice, which lack functional B lymphocytes, develop progressive histopathologic lesions of the submandibular and lachrymal glands similar to NOD mice, but in the absence of autoimmune insulitis and diabetes. Despite the focal appearance of T cells in salivary and lachrymal tissues, NOD.Ig null mice fail to lose secretory function as determined by stimulation of the muscarinic͞cholinergic receptor by the agonist pilocarpine, suggesting a role for B cell autoantibodies in mediating exocrine dryness. Infusion of purified serum IgG or F(ab) 2 fragments from parental NOD mice or human primary Sjögren's syndrome patients, but not serum IgG from healthy controls, alters stimulated saliva production, an observation consistent with antibody binding to neural receptors. Furthermore, human patient IgG fractions competitively inhibited the binding of the muscarinic receptor agonist, [ 3 H]quinuclidinyl benzilate, to salivary gland membranes. This autoantibody activity is lost after preadsorption with intact salivary cells. These findings indicate that autoantibodies play an important part in the functional impairment of secretory processes seen in connection with the autoimmune exocrinopathy of Sjögren's syndrome.
Sjögren’s syndrome: still not fully understood disease
Rheumatology International, 2014
hyper-reactivity and polyclonal production of immunoglobulins, and as a consequence, autoantibodies against pSS affected exocrine glands, especially lacrimal glands and salivary glands, but also other external glands such as the pancreas, mucous glands of the gastrointestinal and respiratory tract or bile secretion. In some patients, abnormal H+ secretion in the distal tubules has also been observed and caused distal renal tubular acidosis (type 1 RTA). In connection with the clinical symptoms which will result from the degree of attachment of these glands and epithelial injury, the pSS often uses the term "autoimmune epithelitis" or "autoimmune exocrinopathy" for better imaging of primary initiation sites of inflammation and autoimmunization. A brief history First lacrimal and salivary glands enlargement was described in a lecture of a Polish surgeon Jan Mikulicz-Radecki in 1888. In 1925, French dermatologists Henri Gougerot described a few cases of atrophy of the salivary glands with dryness of eyes, mouth and vagina. Later in 1933, Swedish ophthalmologists Henrik Sjögren in his doctoral thesis described keratoconjunctivitis sicca, and his description became a basis for pSS picture. Epidemiology It is estimated that primary Sjögren's syndrome occurs from 0.1 to 3.0 % in general population. The disease is more common for women (female/male ratio 9:1), mainly between the ages of 40-60, with the disease most frequently occurring around 50 years of age. Pathogenesis of pSS is not clear, nowadays several factors responsible for the development of the disease, such as Abstract Primary Sjögren's syndrome is an autoimmune disorder with external exocrine glands dysfunction and multiorgan involvement. The pathogenesis of primary Sjogren's syndrome is still unclear; however, our knowledge of the involvement of different cells (e.g., B and T cells, macrophages and dendritic cells) and pathways (BAFF/APRIL and interferons) leading to the development of autoimmunity is continually expanding. For clinicians, the most frequent symptoms are dryness of eyes and mouth, but often the patients have musculoskeletal symptoms and systemic manifestations. However, the increased risk of lymphoproliferative disorders in this group of patients, most commonly B-cell marginal zone lymphoma, is particularly important. Recent separation of IgG4-related diseases and attempts to create further diagnostic criteria for pSS testify to the difficulties, and at the same time a large interest, in understanding the disease so as to allow the effective treatment. This article draws attention to the problems faced by the clinician wishing to securely identify pSS by using accurate laboratory biomarkers and useful imaging tools and predict the development of complications associated with this, still not fully understood, autoimmune disease.
Contribution to the diagnosis and pathophysiology of Sjögren's syndrome
2012
Le syndrome de Sjogren (SS) est une maladie auto-immunitaire caracterisee par une infiltration lymphocytaire des glandes exocrines menant le plus souvent, a une xerophtalmie et a une xerostomie. La physiopathologie de la maladie est complexe et malgre les progres realises, il existe beaucoup de questions a repondre. Classiquement, le syndrome sec qui caracterise la maladie resulterait d’un double processus ou dans un premier temps, la glande serait envahie par des cellules lymphoplasmocytaires puis secondairement detruite. Des avancees recentes dans la physiopathologie de la maladie ont demontre le role de nouvelles molecules, Aquaporine 5 (AQP5) et anticorps muscariniques, qui peuvent contribuer au syndrome sec. Dans ce travail, nous avons etudie des marqueurs diagnostiques de la maladie. Nous avons montre que 2 alarmines, HMGB1 et S100A8/A9 sont augmentes mais ne presentent pas de correlation avec le score d’activite de la maladie. Utilisant differents modeles animaux de SS, nous ...
Sjögren’s syndrome: a systemic autoimmune disease
Clinical and Experimental Medicine, 2021
Sjögren's syndrome is a chronic autoimmune disease characterized by ocular and oral dryness resulting from lacrimal and salivary gland dysfunction. Besides, a variety of systemic manifestations may occur, involving virtually any organ system. As a result, the disease is characterized by pleomorphic clinical manifestations whose characteristics and severity may vary greatly from one patient to another. Sjögren's syndrome can be defined as primary or secondary, depending on whether it occurs alone or in association with other systemic autoimmune diseases, respectively. The pathogenesis of Sjögren's syndrome is still elusive, nevertheless, different, not mutually exclusive, models involving genetic and environmental factors have been proposed to explain its development. Anyhow, the emergence of aberrant autoreactive B-lymphocytes, conducting to autoantibody production and immune complex formation, seems to be crucial in the development of the disease. The diagnosis of Sjögren's syndrome is based on characteristic clinical signs and symptoms, as well as on specific tests including salivary gland histopathology and autoantibodies. Recently, new classification criteria and disease activity scores have been developed primarily for research purposes and they can also be useful tools in everyday clinical practice. Treatment of Sjögren's syndrome ranges from local and symptomatic therapies aimed to control dryness to systemic medications, including disease-modifying agents and biological drugs. The objective of this review paper is to summarize the recent literature on Sjögren's syndrome, starting from its pathogenesis to current therapeutic options.