Materiały źródłowe

• #1 Pathophysiology of Sjögren’s syndrome – PubMed

  https://pubmed.ncbi.nlm.nih.gov/17045106/

  The term Sjgren’s syndrome refers to keratoconjunctivitis sicca and xerostomia due to lymphocytic infiltrates of lachrymal and salivary glands. […] Primary Sjgren’s syndrome is an autoimmune disorder characterized by lymphocytic infiltrates and destruction of the salivary and lachrymal glands and systemic production of autoantibodies to the ribonucleoprotein particles SS-A/Ro and SS-B/La. […] The infiltrating cells (T- and B-cells, dendritic cells) interfere with glandular function at several points: destruction of glandular elements by cell-mediated mechanisms; secretion of cytokines that activate pathways bearing the signature of type 1 and 2 interferons; production of autoantibodies that interfere with muscarinic receptors; and secretion of metalloproteinases (MMPs) that interfere with the interaction of the glandular cell with its extracellular matrix, which is necessary for efficient glandular function. […] Despite extensive study of the underlying cause of Sjgren’s syndrome, the pathogenesis remains obscure. In broad terms, pathogenesis is multifactorial; environmental factors are thought to trigger inflammation in individuals with a genetic predisposition to the disorder.

• #2 Sjogren Syndrome: Practice Essentials, Etiology, Epidemiology

  https://emedicine.medscape.com/article/332125-overview

  Sjgren syndrome is a systemic chronic inflammatory disorder characterized by lymphocytic infiltrates in exocrine organs. […] The etiology of Sjgren syndrome is not well understood. The presence of activated salivary gland epithelial cells expressing major histocompatibility complex (MHC) class II molecules and the identification of inherited susceptibility markers suggest that environmental or endogenous antigens trigger a self-perpetuating inflammatory response in susceptible individuals. In addition, the continuing presence of active interferon pathways in Sjgren syndrome suggests ongoing activation of the innate immune system. […] Current studies have also focused on the role of apoptotic mechanisms in the pathogenesis of primary Sjgren syndrome. A defect in Fas-mediated apoptosis, which is necessary for down-regulation of the immune response, can result in a chronic inflammatory destruction of the salivary gland, resembling Sjgren syndrome.

• #3 Sjögren Syndrome: New Insights in the Pathogenesis and Role of Nuclear Medicine

  https://www.mdpi.com/2077-0383/11/17/5227

  The pathogenesis of SS is complex, some fundamental concepts are in construction and are still a matter of controversy; the lack of hard evidence has not been a barrier for different authors to approach the subject through theoretical models, which have been based on the results of observational studies in humans and in preclinical data. […] Several factors have been implicated in the etiology of SS, as follows: […] The importance of type I interferon has been recognized in the pathogenesis of SS. In pSS, labial salivary gland and peripheral blood gene expression microarray studies, have demonstrated dysregulation of type I interferon-inducible genes. […] SS pathophysiology includes concurrent dysregulation of an innate and adaptative immune pathway involving cell-mediated and humoral disease processes that are incompletely understood.

• #4 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  Enhanced activity of the type-1 IFN system has been linked to multiple autoimmune diseases, including Sjgren’s syndrome. […] The presence of IFN signature was confirmed in both PBMCs and whole blood in a study that analyzed peripheral blood gene expression profiles in Sjgren’s syndrome. […] One of the cytokines upregulated by IFN is BAFF. […] Autonomic nervous system (ANS) abnormalities are common in Sjgren’s syndrome and may play an etiologic role in its pathogenesis. […] Sjgren’s syndrome mimics several ANS failure syndromes. […] Antimuscarinic acetylcholine receptor autoantibodies, or antibodies interfering with the other neurotransmitters and their receptors, would provide a link between autoimmunity and exocrine dysfunction in Sjgren’s syndrome. […] Recent discoveries from studies in patients with Sjgren’s syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the ANS. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjgren’s syndrome.

• #5 Pathogenesis of Sjögren’s disease – UpToDate

  https://www.uptodate.com/contents/pathogenesis-of-sjogrens-disease

  Pathogenesis of Sjögren’s disease […] The pathogenesis of SjD is thought to be a multistep process, triggered by an environmental factor, most likely viral, in a genetically predisposed individual. An immune response involving innate and adaptive immunity, leading to autoimmunity and chronic inflammation, are central components of the disease process. […] The pathogenesis of SjD is typically modeled as a multistep process, triggered by an environmental factor, most likely viral, in a genetically predisposed individual. The initial events engage the innate immune system, but propagation and perpetuation of the autoimmune process require a continual interplay between the innate and adaptive immune systems. […] The result is autoreactive B-cell stimulation, autoantibody production, and chronic inflammation of the salivary and lacrimal glands and other tissues. Extraglandular manifestations may arise from autoimmune exocrinopathy akin to that in the salivary glands (eg, interstitial nephritis, biliary cholangitis), immune-complex deposition (eg, cryoglobulinemic vasculitis), and extranodal lymphoproliferation (eg, lymphocytic interstitial pneumonitis). Chronic stimulation of B cells in the target tissue may promote lymphomagenesis, again through a multistep process in a genetically susceptible individual.

• #6 Pathogenesis of Sjögren’s disease – UpToDate

  https://www.uptodate.com/contents/pathogenesis-of-sjogrens-disease

  Pathogenesis of Sjögren’s disease […] The pathogenesis of SjD is thought to be a multistep process, triggered by an environmental factor, most likely viral, in a genetically predisposed individual. An immune response involving innate and adaptive immunity, leading to autoimmunity and chronic inflammation, are central components of the disease process. […] The pathogenesis of SjD is typically modeled as a multistep process, triggered by an environmental factor, most likely viral, in a genetically predisposed individual. The initial events engage the innate immune system, but propagation and perpetuation of the autoimmune process require a continual interplay between the innate and adaptive immune systems. […] The result is autoreactive B-cell stimulation, autoantibody production, and chronic inflammation of the salivary and lacrimal glands and other tissues. Extraglandular manifestations may arise from autoimmune exocrinopathy akin to that in the salivary glands (eg, interstitial nephritis, biliary cholangitis), immune-complex deposition (eg, cryoglobulinemic vasculitis), and extranodal lymphoproliferation (eg, lymphocytic interstitial pneumonitis). Chronic stimulation of B cells in the target tissue may promote lymphomagenesis, again through a multistep process in a genetically susceptible individual.

• #7

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  Interestingly, some authors found a correlation between EBV presence, disease severity and extra-glandular manifestations. […] Genetic factors are supposed to play an important role in SS pathogenesis. […] Familial association studies showed that about one-third of SS patients have a relative with another connective tissue disease. […] More recently, associations between certain Human Leukocyte Antigen (HLA) alleles (e.g., HLA DRB1*03:01, DQA1*05:01, DQB1*02:01) and SS susceptibility have been demonstrated by genomic studies. […] It is widely accepted that epigenetic factors play an important role in autoimmune disorders. […] Nowadays, epithelial cells are considered major players in the pathogenesis of SS, so that the term autoimmune „epithelitis” is increasingly used to describe this condition.

• #8

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  Interestingly, some authors found a correlation between EBV presence, disease severity and extra-glandular manifestations. […] Genetic factors are supposed to play an important role in SS pathogenesis. […] Familial association studies showed that about one-third of SS patients have a relative with another connective tissue disease. […] More recently, associations between certain Human Leukocyte Antigen (HLA) alleles (e.g., HLA DRB1*03:01, DQA1*05:01, DQB1*02:01) and SS susceptibility have been demonstrated by genomic studies. […] It is widely accepted that epigenetic factors play an important role in autoimmune disorders. […] Nowadays, epithelial cells are considered major players in the pathogenesis of SS, so that the term autoimmune „epithelitis” is increasingly used to describe this condition.

• #9

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  Interestingly, some authors found a correlation between EBV presence, disease severity and extra-glandular manifestations. […] Genetic factors are supposed to play an important role in SS pathogenesis. […] Familial association studies showed that about one-third of SS patients have a relative with another connective tissue disease. […] More recently, associations between certain Human Leukocyte Antigen (HLA) alleles (e.g., HLA DRB1*03:01, DQA1*05:01, DQB1*02:01) and SS susceptibility have been demonstrated by genomic studies. […] It is widely accepted that epigenetic factors play an important role in autoimmune disorders. […] Nowadays, epithelial cells are considered major players in the pathogenesis of SS, so that the term autoimmune „epithelitis” is increasingly used to describe this condition.

• #10 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  This study included data from a discovery cohort of 395 patients of European ancestry with primary Sjgren’s disease, and 1,975 healthy control individuals, and from a replication study that comprised 1,234 cases and 4,779 healthy controls. […] Associations with polymorphisms located at six independent loci were also detected; IRF5, STAT4, BLK, IL12A, TNIP1, and CXCR5. […] This also suggested the activation of the innate immune system, notably through the IFN system, B-cell activation through CXCR5-directed recruitment to lymphoid follicles and B-cell receptor (BCR) activation involving BLK, and T-cell activation owing to HLA susceptibility and the IL-12-IFN–axis. […] Beyond genetics, epigenetic abnormality related to DNA methylation, histone acetylation, or microRNA expression probably has a key role in the pathogenesis of autoimmune diseases, including Sjgren’s disease, though research in this area is very limited.

• #11 Sjogren’s Syndrome – Rheumatology Advisor

  https://www.rheumatologyadvisor.com/ddi/sjogrens-syndrome/

  Sjogrens syndrome is a chronic autoimmune condition caused by lymphocytic infiltration into the exocrine glands and other organs. It is characterized by dry mouth and dry eyes from involvement of the salivary and lacrimal glands as well as a variety of extraglandular manifestations. […] Infectious agents, particularly viruses, may play a role in Sjogrens syndrome etiology. Viruses are hypothesized to increase autoantibody formation by molecular mimicry, which results in tissue damage. […] Certain viruses such as HCV, HIV, Epstein-Barr virus, cytomegalovirus, human T-lymphotropic virus type 1, human herpesvirus 6, and coxsackievirus are proposed as possible inducers of Sjogrens syndrome given that they may cause persistent infection of the salivary glands, leading to organ damage. […] The presence of Sjgrens syndrome is considered a high-risk category in pregnancy, because the disease can cause complications resulting in premature deliveries and spontaneous abortions.

• #12 Sjogren’s Syndrome – Rheumatology Advisor

  https://www.rheumatologyadvisor.com/ddi/sjogrens-syndrome/

  Sjogrens syndrome is a chronic autoimmune condition caused by lymphocytic infiltration into the exocrine glands and other organs. It is characterized by dry mouth and dry eyes from involvement of the salivary and lacrimal glands as well as a variety of extraglandular manifestations. […] Infectious agents, particularly viruses, may play a role in Sjogrens syndrome etiology. Viruses are hypothesized to increase autoantibody formation by molecular mimicry, which results in tissue damage. […] Certain viruses such as HCV, HIV, Epstein-Barr virus, cytomegalovirus, human T-lymphotropic virus type 1, human herpesvirus 6, and coxsackievirus are proposed as possible inducers of Sjogrens syndrome given that they may cause persistent infection of the salivary glands, leading to organ damage. […] The presence of Sjgrens syndrome is considered a high-risk category in pregnancy, because the disease can cause complications resulting in premature deliveries and spontaneous abortions.

• #13 Sjogren’s Syndrome – Rheumatology Advisor

  https://www.rheumatologyadvisor.com/ddi/sjogrens-syndrome/

  Sjogrens syndrome is a chronic autoimmune condition caused by lymphocytic infiltration into the exocrine glands and other organs. It is characterized by dry mouth and dry eyes from involvement of the salivary and lacrimal glands as well as a variety of extraglandular manifestations. […] Infectious agents, particularly viruses, may play a role in Sjogrens syndrome etiology. Viruses are hypothesized to increase autoantibody formation by molecular mimicry, which results in tissue damage. […] Certain viruses such as HCV, HIV, Epstein-Barr virus, cytomegalovirus, human T-lymphotropic virus type 1, human herpesvirus 6, and coxsackievirus are proposed as possible inducers of Sjogrens syndrome given that they may cause persistent infection of the salivary glands, leading to organ damage. […] The presence of Sjgrens syndrome is considered a high-risk category in pregnancy, because the disease can cause complications resulting in premature deliveries and spontaneous abortions.

• #14 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  Environmental factors, such as glandular viral infection, could prompt epithelial cells to activate the HLA-independent innate immune system through toll-like receptors. […] Although several infectious, exogenous agents have been implicated in the pathogenesis of Sjgren’s disease, such as Epstein-Barr virus (EBV), human T-lymphotropic virus 1, and hepatitis C virus, their association with Sjgren’s disease appears weak. […] While EBV is present in the salivary glands of normal individuals, a high incidence of EBV reactivation in Sjgren’s patients has been reported with increased levels of EBV DNA. […] This indicates viral reactivation and the inability of lymphoid infiltrates to control EBV replication in Sjgren’s disease, leading to the initiation or perpetuation of an immune response in target organs.

• #15

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  More specifically, a derangement of the innate immune barriers has a pivotal role in SS pathogenesis, especially in the early phases of the disease, through a mechanism involving the interferon (IFN) pathway. […] On the other hand, the adaptive immune system has a central role in SS development. […] Indeed, persistent B-cells activation and the proliferation of Th1 and Th17 cells contribute to the progression of the disease. […] Finally, in recent years, researchers focused on epithelial cells functioning, which demonstrated to be relevant factors of this complex pathogenetic scenario. […] Different infectious agents, especially viruses, have been considered potential SS pathogenetic triggers. […] Among them, Epstein-Barr virus (EBV) was found in lacrimal gland biopsies, as well as in saliva and salivary gland specimens.

• #16

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  Interestingly, some authors found a correlation between EBV presence, disease severity and extra-glandular manifestations. […] Genetic factors are supposed to play an important role in SS pathogenesis. […] Familial association studies showed that about one-third of SS patients have a relative with another connective tissue disease. […] More recently, associations between certain Human Leukocyte Antigen (HLA) alleles (e.g., HLA DRB1*03:01, DQA1*05:01, DQB1*02:01) and SS susceptibility have been demonstrated by genomic studies. […] It is widely accepted that epigenetic factors play an important role in autoimmune disorders. […] Nowadays, epithelial cells are considered major players in the pathogenesis of SS, so that the term autoimmune „epithelitis” is increasingly used to describe this condition.

• #17 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  Environmental factors, such as glandular viral infection, could prompt epithelial cells to activate the HLA-independent innate immune system through toll-like receptors. […] Although several infectious, exogenous agents have been implicated in the pathogenesis of Sjgren’s disease, such as Epstein-Barr virus (EBV), human T-lymphotropic virus 1, and hepatitis C virus, their association with Sjgren’s disease appears weak. […] While EBV is present in the salivary glands of normal individuals, a high incidence of EBV reactivation in Sjgren’s patients has been reported with increased levels of EBV DNA. […] This indicates viral reactivation and the inability of lymphoid infiltrates to control EBV replication in Sjgren’s disease, leading to the initiation or perpetuation of an immune response in target organs.

• #18

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  More specifically, a derangement of the innate immune barriers has a pivotal role in SS pathogenesis, especially in the early phases of the disease, through a mechanism involving the interferon (IFN) pathway. […] On the other hand, the adaptive immune system has a central role in SS development. […] Indeed, persistent B-cells activation and the proliferation of Th1 and Th17 cells contribute to the progression of the disease. […] Finally, in recent years, researchers focused on epithelial cells functioning, which demonstrated to be relevant factors of this complex pathogenetic scenario. […] Different infectious agents, especially viruses, have been considered potential SS pathogenetic triggers. […] Among them, Epstein-Barr virus (EBV) was found in lacrimal gland biopsies, as well as in saliva and salivary gland specimens.

• #19 Advances in understanding the pathogenesis of primary Sjögren’s syndrome | Nature Reviews RheumatologyClose bannerClose banner

  https://www.nature.com/articles/nrrheum.2013.110

  Primary Sjögren’s syndrome (pSS) is a prototypic autoimmune disorder, management of which has long suffered from a lack of knowledge of the underlying pathophysiological mechanisms; however, over the past decade major advances have been made in understanding the pathogenesis of pSS. […] The innate immune system has been demonstrated to have an important role at the early stage of the disease, notably through activation of the type I interferon (IFN) system. […] In addition, mechanisms of B-cell activation in pSS have become clearer, particularly owing to recognition of the involvement of the TNF family cytokine B-cell-activating factor, production of which is highly dependent on expression of type I and type II IFNs. […] Moreover, key inroads have been made in understanding lymphomagenesis, the most severe complication of pSS.

• #20 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  Recent studies of animal models of Sjgren’s syndrome revealed the complex interaction between innate and adaptive immunity and salivary gland dysfunction. They showed that although frequently coexisting, inflammation and dysfunction may be discordant and primary abnormalities in either may lead to abnormalities in the other. […] This was associated with sialoadenitis but without evidence of robust adaptive autoimmune response in the early stages of the disease. […] Moreover, Toll-like receptor 3 (TLR3) activation associated with type-1 interferon (IFN) upregulation led to rapid onset, reversible hyposalivation without glandular inflammation, suggesting that salivary gland dysfunction may precede autoimmunity or represent a separate process in the pathogenesis of Sjgren’s syndrome. […] One study found increased caspase-11 in macrophages, signal transducer and activator of transcription 1 (STAT-1) and caspase-1 in apoptotic epithelial cells and elevated salivary levels of cytokines of innate immunity such as interleukin (IL)-18 before the development of the disease.

• #21

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  Indeed, epithelial cells play a double role in SS pathogenesis, because they represent the target of the autoimmune process, but also the triggers of the immune activation. […] An over-expression of IFN-inducible genes, also known as IFN-signature, was demonstrated among patients with SS, both in peripheral blood and salivary glands. […] Intriguingly, an interaction between the IFN pathway and B lymphocyte activation has been proposed. […] This cross-talk seems bi-directional, since B cells could induce the production of IFN, which in turn would be able to favor auto-antibodies production. […] Finally, a significant correlation between BAFF (both as serum level and mRNA expression) and type I IFN signature has been described in SS, thus representing a potential therapeutic target.

• #22 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  Enhanced activity of the type-1 IFN system has been linked to multiple autoimmune diseases, including Sjgren’s syndrome. […] The presence of IFN signature was confirmed in both PBMCs and whole blood in a study that analyzed peripheral blood gene expression profiles in Sjgren’s syndrome. […] One of the cytokines upregulated by IFN is BAFF. […] Autonomic nervous system (ANS) abnormalities are common in Sjgren’s syndrome and may play an etiologic role in its pathogenesis. […] Sjgren’s syndrome mimics several ANS failure syndromes. […] Antimuscarinic acetylcholine receptor autoantibodies, or antibodies interfering with the other neurotransmitters and their receptors, would provide a link between autoimmunity and exocrine dysfunction in Sjgren’s syndrome. […] Recent discoveries from studies in patients with Sjgren’s syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the ANS. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjgren’s syndrome.

• #23 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  Enhanced activity of the type-1 IFN system has been linked to multiple autoimmune diseases, including Sjgren’s syndrome. […] The presence of IFN signature was confirmed in both PBMCs and whole blood in a study that analyzed peripheral blood gene expression profiles in Sjgren’s syndrome. […] One of the cytokines upregulated by IFN is BAFF. […] Autonomic nervous system (ANS) abnormalities are common in Sjgren’s syndrome and may play an etiologic role in its pathogenesis. […] Sjgren’s syndrome mimics several ANS failure syndromes. […] Antimuscarinic acetylcholine receptor autoantibodies, or antibodies interfering with the other neurotransmitters and their receptors, would provide a link between autoimmunity and exocrine dysfunction in Sjgren’s syndrome. […] Recent discoveries from studies in patients with Sjgren’s syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the ANS. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjgren’s syndrome.

• #24 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  The early accumulation of plasmacytoid dendritic cells in the target tissues, which produce high levels of type 1 IFNs, seems important, as these cells can further dysregulate the immune response through abnormal retention of lymphocytes in the tissues, and their subsequent activation. […] IFN- stimulates the production of B-cell activating factor (BAFF) by epithelial cells, DCs, and T cells. […] BAFF stimulates aberrant B-cell maturation, leading to the emergence of self-reactive B cells, which locally produce autoantibodies, in a germinal centre-like structure (GC-like), which is also the location of lymphomagenesis (origin of lymphoma). […] Dysregulation of apoptosis (programmed cell death) is believed to play a role in the pathogenesis of a variety of autoimmune diseases, though its role in Sjgren’s disease is controversial.

• #25 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  Enhanced activity of the type-1 IFN system has been linked to multiple autoimmune diseases, including Sjgren’s syndrome. […] The presence of IFN signature was confirmed in both PBMCs and whole blood in a study that analyzed peripheral blood gene expression profiles in Sjgren’s syndrome. […] One of the cytokines upregulated by IFN is BAFF. […] Autonomic nervous system (ANS) abnormalities are common in Sjgren’s syndrome and may play an etiologic role in its pathogenesis. […] Sjgren’s syndrome mimics several ANS failure syndromes. […] Antimuscarinic acetylcholine receptor autoantibodies, or antibodies interfering with the other neurotransmitters and their receptors, would provide a link between autoimmunity and exocrine dysfunction in Sjgren’s syndrome. […] Recent discoveries from studies in patients with Sjgren’s syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the ANS. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjgren’s syndrome.

• #26 Advances in understanding the pathogenesis of primary Sjögren’s syndrome | Nature Reviews RheumatologyClose bannerClose banner

  https://www.nature.com/articles/nrrheum.2013.110

  IL-12 production and subsequent T-cell activation, mainly IFN-γ-secreting type 1 T-helper cells, have also been implicated in disease pathogenesis. […] Furthermore, evidence implicates neuroendocrine system dysfunction in pSS pathogenesis. […] Environmental triggers promote activation of the innate immune system and the production of interferons (IFNs), which, in susceptible individuals, represent the first stages of primary Sjögren’s syndrome (pSS) pathogenesis. […] B-cell-activating factor is induced by type I and type II IFNs and has a key role in activating autoreactive B cells; other cytokines such IL-21 could also be important for this process. […] Continuous B-cell activation as a result of the autoimmune response and subtle deficiencies in the control of nuclear factor κB activation might underlie increased lymphomagenesis associated with pSS.

• #27

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  Indeed, epithelial cells play a double role in SS pathogenesis, because they represent the target of the autoimmune process, but also the triggers of the immune activation. […] An over-expression of IFN-inducible genes, also known as IFN-signature, was demonstrated among patients with SS, both in peripheral blood and salivary glands. […] Intriguingly, an interaction between the IFN pathway and B lymphocyte activation has been proposed. […] This cross-talk seems bi-directional, since B cells could induce the production of IFN, which in turn would be able to favor auto-antibodies production. […] Finally, a significant correlation between BAFF (both as serum level and mRNA expression) and type I IFN signature has been described in SS, thus representing a potential therapeutic target.

• #28

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  Interestingly, some authors found a correlation between EBV presence, disease severity and extra-glandular manifestations. […] Genetic factors are supposed to play an important role in SS pathogenesis. […] Familial association studies showed that about one-third of SS patients have a relative with another connective tissue disease. […] More recently, associations between certain Human Leukocyte Antigen (HLA) alleles (e.g., HLA DRB1*03:01, DQA1*05:01, DQB1*02:01) and SS susceptibility have been demonstrated by genomic studies. […] It is widely accepted that epigenetic factors play an important role in autoimmune disorders. […] Nowadays, epithelial cells are considered major players in the pathogenesis of SS, so that the term autoimmune „epithelitis” is increasingly used to describe this condition.

• #29 Advances in understanding the pathogenesis of primary Sjögren’s syndrome | Nature Reviews RheumatologyClose bannerClose banner

  https://www.nature.com/articles/nrrheum.2013.110

  IL-12 is a central cytokine in pSS pathogenesis, promoting activation of the type II IFN system via both the innate (natural killer cells) and the adaptive (type 1 T-helper cells) immune systems. […] Epithelial cells are major players in pSS pathogenesis, not only as targets of disease, but also as drivers of the disease process that promote overactivation of the immune system. […] Many similarities exist between systemic lupus erythematosus and pSS pathogenesis; the main pathogenetic difference is the mucosa tropism of pSS, the basis for which remains unknown.

• #30

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  Indeed, epithelial cells play a double role in SS pathogenesis, because they represent the target of the autoimmune process, but also the triggers of the immune activation. […] An over-expression of IFN-inducible genes, also known as IFN-signature, was demonstrated among patients with SS, both in peripheral blood and salivary glands. […] Intriguingly, an interaction between the IFN pathway and B lymphocyte activation has been proposed. […] This cross-talk seems bi-directional, since B cells could induce the production of IFN, which in turn would be able to favor auto-antibodies production. […] Finally, a significant correlation between BAFF (both as serum level and mRNA expression) and type I IFN signature has been described in SS, thus representing a potential therapeutic target.

• #31 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  Epithelial cells in Sjgren’s disease lesions are active participants in the induction and perpetuation of the inflammatory process. […] Environmental and hormonal factors, in concert with an appropriate genetic background, are believed to trigger Sjgren’s disease, which dysregulates epithelial cells and allows aberrant homing and activation of dendritic cells (DCs), T cells, and B cells. […] Dendritic cells are antigen-presenting cells that process antigen material and present it to other T cells. […] Following the migration of lymphocytes into the glands in response to chemokines and specific adhesion molecules, T cells interact with epithelial cells. […] Epithelial cells are further activated by proinflammatory cytokines (IL-1, IFN-, and TNF), which are produced by adjacent T cells.

• #32 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  Epithelial cells in Sjgren’s disease lesions are active participants in the induction and perpetuation of the inflammatory process. […] Environmental and hormonal factors, in concert with an appropriate genetic background, are believed to trigger Sjgren’s disease, which dysregulates epithelial cells and allows aberrant homing and activation of dendritic cells (DCs), T cells, and B cells. […] Dendritic cells are antigen-presenting cells that process antigen material and present it to other T cells. […] Following the migration of lymphocytes into the glands in response to chemokines and specific adhesion molecules, T cells interact with epithelial cells. […] Epithelial cells are further activated by proinflammatory cytokines (IL-1, IFN-, and TNF), which are produced by adjacent T cells.

• #33 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  Epithelial cells in Sjgren’s disease lesions are active participants in the induction and perpetuation of the inflammatory process. […] Environmental and hormonal factors, in concert with an appropriate genetic background, are believed to trigger Sjgren’s disease, which dysregulates epithelial cells and allows aberrant homing and activation of dendritic cells (DCs), T cells, and B cells. […] Dendritic cells are antigen-presenting cells that process antigen material and present it to other T cells. […] Following the migration of lymphocytes into the glands in response to chemokines and specific adhesion molecules, T cells interact with epithelial cells. […] Epithelial cells are further activated by proinflammatory cytokines (IL-1, IFN-, and TNF), which are produced by adjacent T cells.

• #34 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  The early accumulation of plasmacytoid dendritic cells in the target tissues, which produce high levels of type 1 IFNs, seems important, as these cells can further dysregulate the immune response through abnormal retention of lymphocytes in the tissues, and their subsequent activation. […] IFN- stimulates the production of B-cell activating factor (BAFF) by epithelial cells, DCs, and T cells. […] BAFF stimulates aberrant B-cell maturation, leading to the emergence of self-reactive B cells, which locally produce autoantibodies, in a germinal centre-like structure (GC-like), which is also the location of lymphomagenesis (origin of lymphoma). […] Dysregulation of apoptosis (programmed cell death) is believed to play a role in the pathogenesis of a variety of autoimmune diseases, though its role in Sjgren’s disease is controversial.

• #35 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  The early accumulation of plasmacytoid dendritic cells in the target tissues, which produce high levels of type 1 IFNs, seems important, as these cells can further dysregulate the immune response through abnormal retention of lymphocytes in the tissues, and their subsequent activation. […] IFN- stimulates the production of B-cell activating factor (BAFF) by epithelial cells, DCs, and T cells. […] BAFF stimulates aberrant B-cell maturation, leading to the emergence of self-reactive B cells, which locally produce autoantibodies, in a germinal centre-like structure (GC-like), which is also the location of lymphomagenesis (origin of lymphoma). […] Dysregulation of apoptosis (programmed cell death) is believed to play a role in the pathogenesis of a variety of autoimmune diseases, though its role in Sjgren’s disease is controversial.

• #36

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  More specifically, a derangement of the innate immune barriers has a pivotal role in SS pathogenesis, especially in the early phases of the disease, through a mechanism involving the interferon (IFN) pathway. […] On the other hand, the adaptive immune system has a central role in SS development. […] Indeed, persistent B-cells activation and the proliferation of Th1 and Th17 cells contribute to the progression of the disease. […] Finally, in recent years, researchers focused on epithelial cells functioning, which demonstrated to be relevant factors of this complex pathogenetic scenario. […] Different infectious agents, especially viruses, have been considered potential SS pathogenetic triggers. […] Among them, Epstein-Barr virus (EBV) was found in lacrimal gland biopsies, as well as in saliva and salivary gland specimens.

• #37 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  Sjgren’s disease is associated with increased levels in cerebrospinal fluid (CSF) of IL-1RA, an interleukin 1 antagonist. […] This suggests that the disease begins with increased activity in the interleukin 1 system, followed by an autoregulatory upregulation of IL-1RA to reduce the successful binding of interleukin 1 to its receptors. […] Interleukin 1 likely is the marker for fatigue, but increased IL-1RA is observed in the CSF and is associated with increased fatigue through cytokine-induced sickness behavior. […] However, Sjgren’s disease is characterized by decreased levels of IL-1ra in saliva, which could be responsible for mouth inflammation and dryness. […] The genetic locus most significantly associated with primary SS is the major histocompatibility complex/human leukocyte antigen (MHC/HLA) region, as demonstrated by the preliminary results of the first genome-wide association study.

• #38 Diagnosis and Management of Sjögren Syndrome | AAFP

  https://www.aafp.org/pubs/afp/issues/2009/0315/p465.html

  The pathogenesis of Sjgren syndrome is obscure. It is probably the result of an environmental stimulus that promotes an auto-immune reaction in genetically susceptible persons. Infectious agentsmost commonly sialotropic viruseshave been postulated to trigger the syndrome; however, associations with most of the potential viral candidates, including cytomegalovirus and Epstein-Barr virus, are weak. Serologic studies show an association between primary Sjgren syndrome and HLA-DR haplotypes. […] Sjgren syndrome represents a complex, multifaceted activation of the immune system. B-lymphocyte dysregulation and hyper-activity play a major role in the disease. The histological hallmark of Sjgren syndrome is lymphocytic infiltration of the exocrine glands, which leads to acinar gland degeneration, necrosis, atrophy, and decreasing lacrimosalivary function. Glandular neurodegeneration is also present, which may explain why patients experience sicca syndrome when more than 50 percent of the glandular epithelial cells remain intact.

• #39 Advances in understanding the pathogenesis of primary Sjögren’s syndrome | Nature Reviews RheumatologyClose bannerClose banner

  https://www.nature.com/articles/nrrheum.2013.110

  IL-12 production and subsequent T-cell activation, mainly IFN-γ-secreting type 1 T-helper cells, have also been implicated in disease pathogenesis. […] Furthermore, evidence implicates neuroendocrine system dysfunction in pSS pathogenesis. […] Environmental triggers promote activation of the innate immune system and the production of interferons (IFNs), which, in susceptible individuals, represent the first stages of primary Sjögren’s syndrome (pSS) pathogenesis. […] B-cell-activating factor is induced by type I and type II IFNs and has a key role in activating autoreactive B cells; other cytokines such IL-21 could also be important for this process. […] Continuous B-cell activation as a result of the autoimmune response and subtle deficiencies in the control of nuclear factor κB activation might underlie increased lymphomagenesis associated with pSS.

• #40 Advances in understanding the pathogenesis of primary Sjögren’s syndrome | Nature Reviews RheumatologyClose bannerClose banner

  https://www.nature.com/articles/nrrheum.2013.110

  IL-12 is a central cytokine in pSS pathogenesis, promoting activation of the type II IFN system via both the innate (natural killer cells) and the adaptive (type 1 T-helper cells) immune systems. […] Epithelial cells are major players in pSS pathogenesis, not only as targets of disease, but also as drivers of the disease process that promote overactivation of the immune system. […] Many similarities exist between systemic lupus erythematosus and pSS pathogenesis; the main pathogenetic difference is the mucosa tropism of pSS, the basis for which remains unknown.

• #41

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  More specifically, a derangement of the innate immune barriers has a pivotal role in SS pathogenesis, especially in the early phases of the disease, through a mechanism involving the interferon (IFN) pathway. […] On the other hand, the adaptive immune system has a central role in SS development. […] Indeed, persistent B-cells activation and the proliferation of Th1 and Th17 cells contribute to the progression of the disease. […] Finally, in recent years, researchers focused on epithelial cells functioning, which demonstrated to be relevant factors of this complex pathogenetic scenario. […] Different infectious agents, especially viruses, have been considered potential SS pathogenetic triggers. […] Among them, Epstein-Barr virus (EBV) was found in lacrimal gland biopsies, as well as in saliva and salivary gland specimens.

• #42

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  Sjgrens syndrome is a chronic autoimmune disease characterized by ocular and oral dryness resulting from lacrimal and salivary gland dysfunction. […] The pathogenesis of Sjgrens 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. […] Similarly to other autoimmune diseases, the etiology of SS is unknown. […] To date, it is widely accepted that exposure to specific environmental factors in susceptible individuals may play a crucial role, thus, leading to the dysregulation of the immune system and disease occurrence.

• #43

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  Sjgrens syndrome is a chronic autoimmune disease characterized by ocular and oral dryness resulting from lacrimal and salivary gland dysfunction. […] The pathogenesis of Sjgrens 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. […] Similarly to other autoimmune diseases, the etiology of SS is unknown. […] To date, it is widely accepted that exposure to specific environmental factors in susceptible individuals may play a crucial role, thus, leading to the dysregulation of the immune system and disease occurrence.

• #44 B cells in the pathogenesis of primary Sjögren syndrome | Nature Reviews RheumatologyClose bannerClose banner

  https://www.nature.com/articles/nrrheum.2018.1

  Genetic risk factors associated with primary Sjögren syndrome (pSS) can promote B cell activation, as can epigenetic changes, which can sometimes affect the same disease-associated genes. […] BAFF (also known as TNF ligand superfamily member 13B) is central to the crosstalk between early activation of the innate immune system and the stimulation of autoreactive B cells. […] CD27+ memory B cells, marginal zone B cells, plasmablasts and plasma cells are the key subsets of B cells involved in the pathogenesis of pSS. […] Target organs (salivary and lachrymal glands) are involved in B cell activation, notably via the formation of germinal centre-like structures within the epithelium and plasma cell niches. […] Continuous stimulation of autoreactive B cells by immune complexes is the first step towards lymphomagenesis associated with pSS.

• #45 B cells in the pathogenesis of primary Sjögren syndrome | Nature Reviews RheumatologyClose bannerClose banner

  https://www.nature.com/articles/nrrheum.2018.1

  Genetic risk factors associated with primary Sjögren syndrome (pSS) can promote B cell activation, as can epigenetic changes, which can sometimes affect the same disease-associated genes. […] BAFF (also known as TNF ligand superfamily member 13B) is central to the crosstalk between early activation of the innate immune system and the stimulation of autoreactive B cells. […] CD27+ memory B cells, marginal zone B cells, plasmablasts and plasma cells are the key subsets of B cells involved in the pathogenesis of pSS. […] Target organs (salivary and lachrymal glands) are involved in B cell activation, notably via the formation of germinal centre-like structures within the epithelium and plasma cell niches. […] Continuous stimulation of autoreactive B cells by immune complexes is the first step towards lymphomagenesis associated with pSS.

• #46 B cells in the pathogenesis of primary Sjögren syndrome | Nature Reviews RheumatologyClose bannerClose banner

  https://www.nature.com/articles/nrrheum.2018.1

  Genetic risk factors associated with primary Sjögren syndrome (pSS) can promote B cell activation, as can epigenetic changes, which can sometimes affect the same disease-associated genes. […] BAFF (also known as TNF ligand superfamily member 13B) is central to the crosstalk between early activation of the innate immune system and the stimulation of autoreactive B cells. […] CD27+ memory B cells, marginal zone B cells, plasmablasts and plasma cells are the key subsets of B cells involved in the pathogenesis of pSS. […] Target organs (salivary and lachrymal glands) are involved in B cell activation, notably via the formation of germinal centre-like structures within the epithelium and plasma cell niches. […] Continuous stimulation of autoreactive B cells by immune complexes is the first step towards lymphomagenesis associated with pSS.

• #47 Sjögren Syndrome: New Insights in the Pathogenesis and Role of Nuclear Medicine

  https://www.mdpi.com/2077-0383/11/17/5227

  Björk et al. have proposed a model to approach the possible pathogenic mechanisms associated with SS, which can be summarized as follows: A trigger (e.g., viral infection) initiates disruption of the salivary gland epithelium, inducing the production of type I IFN, and auto-antigens released by the dying cells create an inflammatory microenvironment. […] Ectopic lymphoid-like structures (ELSs) play an important role in the pathogenesis of rheumatic autoimmune diseases. […] The estimated prevalence of ELSs in SS is 30–40%, frequently around central duct structures, leading to the belief that ELSs may play an important role in antigen recognition and induction of an immune response against ductal epithelial cells. […] The ectopic germinal centers of ELSs are associated with the local production of autoantibodies and have been associated with the maintenance of autoimmunity within a target organ.

• #48 Sjögren Syndrome: New Insights in the Pathogenesis and Role of Nuclear Medicine

  https://www.mdpi.com/2077-0383/11/17/5227

  Björk et al. have proposed a model to approach the possible pathogenic mechanisms associated with SS, which can be summarized as follows: A trigger (e.g., viral infection) initiates disruption of the salivary gland epithelium, inducing the production of type I IFN, and auto-antigens released by the dying cells create an inflammatory microenvironment. […] Ectopic lymphoid-like structures (ELSs) play an important role in the pathogenesis of rheumatic autoimmune diseases. […] The estimated prevalence of ELSs in SS is 30–40%, frequently around central duct structures, leading to the belief that ELSs may play an important role in antigen recognition and induction of an immune response against ductal epithelial cells. […] The ectopic germinal centers of ELSs are associated with the local production of autoantibodies and have been associated with the maintenance of autoimmunity within a target organ.

• #49 Sjögren Syndrome: New Insights in the Pathogenesis and Role of Nuclear Medicine

  https://www.mdpi.com/2077-0383/11/17/5227

  Björk et al. have proposed a model to approach the possible pathogenic mechanisms associated with SS, which can be summarized as follows: A trigger (e.g., viral infection) initiates disruption of the salivary gland epithelium, inducing the production of type I IFN, and auto-antigens released by the dying cells create an inflammatory microenvironment. […] Ectopic lymphoid-like structures (ELSs) play an important role in the pathogenesis of rheumatic autoimmune diseases. […] The estimated prevalence of ELSs in SS is 30–40%, frequently around central duct structures, leading to the belief that ELSs may play an important role in antigen recognition and induction of an immune response against ductal epithelial cells. […] The ectopic germinal centers of ELSs are associated with the local production of autoantibodies and have been associated with the maintenance of autoimmunity within a target organ.

• #50 Sjögren Syndrome: New Insights in the Pathogenesis and Role of Nuclear Medicine

  https://www.mdpi.com/2077-0383/11/17/5227

  There is evidence that in SS patients, the presence of ELSs is associated with disease progression, high levels of circulating autoantibodies, and systemic manifestations, such as lymphadenopathy and peripheral neuropathy. […] The more we investigate the pathogenesis of diseases, the more we understand how to prevent and treat them.

• #51 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  Recent studies of animal models of Sjgren’s syndrome revealed the complex interaction between innate and adaptive immunity and salivary gland dysfunction. They showed that although frequently coexisting, inflammation and dysfunction may be discordant and primary abnormalities in either may lead to abnormalities in the other. […] This was associated with sialoadenitis but without evidence of robust adaptive autoimmune response in the early stages of the disease. […] Moreover, Toll-like receptor 3 (TLR3) activation associated with type-1 interferon (IFN) upregulation led to rapid onset, reversible hyposalivation without glandular inflammation, suggesting that salivary gland dysfunction may precede autoimmunity or represent a separate process in the pathogenesis of Sjgren’s syndrome. […] One study found increased caspase-11 in macrophages, signal transducer and activator of transcription 1 (STAT-1) and caspase-1 in apoptotic epithelial cells and elevated salivary levels of cytokines of innate immunity such as interleukin (IL)-18 before the development of the disease.

• #52 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  Recent studies of animal models of Sjgren’s syndrome revealed the complex interaction between innate and adaptive immunity and salivary gland dysfunction. They showed that although frequently coexisting, inflammation and dysfunction may be discordant and primary abnormalities in either may lead to abnormalities in the other. […] This was associated with sialoadenitis but without evidence of robust adaptive autoimmune response in the early stages of the disease. […] Moreover, Toll-like receptor 3 (TLR3) activation associated with type-1 interferon (IFN) upregulation led to rapid onset, reversible hyposalivation without glandular inflammation, suggesting that salivary gland dysfunction may precede autoimmunity or represent a separate process in the pathogenesis of Sjgren’s syndrome. […] One study found increased caspase-11 in macrophages, signal transducer and activator of transcription 1 (STAT-1) and caspase-1 in apoptotic epithelial cells and elevated salivary levels of cytokines of innate immunity such as interleukin (IL)-18 before the development of the disease.

• #53 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  To summarize recent developments in our understanding of the pathogenesis of Sjgren’s syndrome with a focus on the relationship between inflammation and exocrine dysfunction. […] Activation of the innate immune system can lead to exocrine dysfunction before or without significant inflammation, whereas in other models, salivary gland function is preserved despite intense inflammatory infiltrates. […] Recent discoveries from studies in patients with Sjgren’s syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the autonomic nervous system. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjgren’s syndrome.

• #54 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  To summarize recent developments in our understanding of the pathogenesis of Sjgren’s syndrome with a focus on the relationship between inflammation and exocrine dysfunction. […] Activation of the innate immune system can lead to exocrine dysfunction before or without significant inflammation, whereas in other models, salivary gland function is preserved despite intense inflammatory infiltrates. […] Recent discoveries from studies in patients with Sjgren’s syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the autonomic nervous system. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjgren’s syndrome.

• #55 Primary Sjögren’s syndrome: new perspectives on salivary gland epithelial cells | European Journal of Medical Research | Full Text

  https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-01967-5

  In SGECs from pSS patients, there is an overall decrease in DNA methylation level, contrasting with unaffected levels in T and B cells. […] Consequently, SGEC dysfunction may partly result from altered DNA methylation level. […] The SG possesses a delicate structure that often faces disorder or even destruction in pSS patients. […] Evidence demonstrates that SGECs undergo considerable structural changes in their apical, lateral and basal structure as well as in the ECM, causing loss of barrier function and cell polarity, consequently resulting in dysfunction. […] Inadequate salivation is the culprit of xerostomia in pSS. Extensive research has been conducted over the decades to examine both fluid and protein secretion. […] The deviations may take place in the activation of muscarinic receptor, Ca2+ signaling, and apical channels.

• #56 Primary Sjögren’s syndrome: new perspectives on salivary gland epithelial cells | European Journal of Medical Research | Full Text

  https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-01967-5

  In SGECs from pSS patients, there is an overall decrease in DNA methylation level, contrasting with unaffected levels in T and B cells. […] Consequently, SGEC dysfunction may partly result from altered DNA methylation level. […] The SG possesses a delicate structure that often faces disorder or even destruction in pSS patients. […] Evidence demonstrates that SGECs undergo considerable structural changes in their apical, lateral and basal structure as well as in the ECM, causing loss of barrier function and cell polarity, consequently resulting in dysfunction. […] Inadequate salivation is the culprit of xerostomia in pSS. Extensive research has been conducted over the decades to examine both fluid and protein secretion. […] The deviations may take place in the activation of muscarinic receptor, Ca2+ signaling, and apical channels.

• #57 Primary Sjögren’s syndrome: new perspectives on salivary gland epithelial cells | European Journal of Medical Research | Full Text

  https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-01967-5

  Abnormal protein secretion, particularly mucin exocytosis, may provide some rationale for the occurrence of pSS. […] This could be attributed to both the decreased quality of mucins and aberrations in the trafficking route. […] In summary, the findings indicate that the early development of pSS is accompanied by regenerative processes of BM in SGECs. […] Given the limited efficacy of current immunological treatments, we reckon these findings significant for re-examining the pathogenesis of pSS and developing interventions targeting SGECs in the early stages of the disease.

• #58 Primary Sjögren’s syndrome: new perspectives on salivary gland epithelial cells | European Journal of Medical Research | Full Text

  https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-01967-5

  In SGECs from pSS patients, there is an overall decrease in DNA methylation level, contrasting with unaffected levels in T and B cells. […] Consequently, SGEC dysfunction may partly result from altered DNA methylation level. […] The SG possesses a delicate structure that often faces disorder or even destruction in pSS patients. […] Evidence demonstrates that SGECs undergo considerable structural changes in their apical, lateral and basal structure as well as in the ECM, causing loss of barrier function and cell polarity, consequently resulting in dysfunction. […] Inadequate salivation is the culprit of xerostomia in pSS. Extensive research has been conducted over the decades to examine both fluid and protein secretion. […] The deviations may take place in the activation of muscarinic receptor, Ca2+ signaling, and apical channels.

• #59 Sjögren Syndrome – Musculoskeletal and Connective Tissue Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/systemic-rheumatic-diseases/sj%C3%B6gren-syndrome

  Salivary, lacrimal, and other exocrine glands become infiltrated with CD4+ T cells and with B cells. The T cells produce inflammatory cytokines (eg, interleukin [IL]-2, interferon-gamma). Salivary duct cells also produce cytokines, eventually damaging the secretory ducts. Atrophy of the secretory epithelium of the lacrimal glands causes desiccation of the cornea and conjunctiva (keratoconjunctivitis sicca). […] Lymphocytic infiltration and intraductal cellular proliferation in the parotid gland cause luminal narrowing and in some cases formation of compact cellular structures termed myoepithelial islands; atrophy of the gland can result. Dryness and gastrointestinal mucosal or submucosal atrophy and diffuse infiltration by plasma cells and lymphocytes may cause symptoms (eg, dysphagia).

• #60 Primary Sjögren’s syndrome: new perspectives on salivary gland epithelial cells | European Journal of Medical Research | Full Text

  https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-01967-5

  In SGECs from pSS patients, there is an overall decrease in DNA methylation level, contrasting with unaffected levels in T and B cells. […] Consequently, SGEC dysfunction may partly result from altered DNA methylation level. […] The SG possesses a delicate structure that often faces disorder or even destruction in pSS patients. […] Evidence demonstrates that SGECs undergo considerable structural changes in their apical, lateral and basal structure as well as in the ECM, causing loss of barrier function and cell polarity, consequently resulting in dysfunction. […] Inadequate salivation is the culprit of xerostomia in pSS. Extensive research has been conducted over the decades to examine both fluid and protein secretion. […] The deviations may take place in the activation of muscarinic receptor, Ca2+ signaling, and apical channels.

• #61 Sjögren Syndrome – Musculoskeletal and Connective Tissue Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/systemic-rheumatic-diseases/sj%C3%B6gren-syndrome

  Salivary, lacrimal, and other exocrine glands become infiltrated with CD4+ T cells and with B cells. The T cells produce inflammatory cytokines (eg, interleukin [IL]-2, interferon-gamma). Salivary duct cells also produce cytokines, eventually damaging the secretory ducts. Atrophy of the secretory epithelium of the lacrimal glands causes desiccation of the cornea and conjunctiva (keratoconjunctivitis sicca). […] Lymphocytic infiltration and intraductal cellular proliferation in the parotid gland cause luminal narrowing and in some cases formation of compact cellular structures termed myoepithelial islands; atrophy of the gland can result. Dryness and gastrointestinal mucosal or submucosal atrophy and diffuse infiltration by plasma cells and lymphocytes may cause symptoms (eg, dysphagia).

• #62 Sjögren Syndrome – Musculoskeletal and Connective Tissue Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/systemic-rheumatic-diseases/sj%C3%B6gren-syndrome

  Salivary, lacrimal, and other exocrine glands become infiltrated with CD4+ T cells and with B cells. The T cells produce inflammatory cytokines (eg, interleukin [IL]-2, interferon-gamma). Salivary duct cells also produce cytokines, eventually damaging the secretory ducts. Atrophy of the secretory epithelium of the lacrimal glands causes desiccation of the cornea and conjunctiva (keratoconjunctivitis sicca). […] Lymphocytic infiltration and intraductal cellular proliferation in the parotid gland cause luminal narrowing and in some cases formation of compact cellular structures termed myoepithelial islands; atrophy of the gland can result. Dryness and gastrointestinal mucosal or submucosal atrophy and diffuse infiltration by plasma cells and lymphocytes may cause symptoms (eg, dysphagia).

• #63 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  The early accumulation of plasmacytoid dendritic cells in the target tissues, which produce high levels of type 1 IFNs, seems important, as these cells can further dysregulate the immune response through abnormal retention of lymphocytes in the tissues, and their subsequent activation. […] IFN- stimulates the production of B-cell activating factor (BAFF) by epithelial cells, DCs, and T cells. […] BAFF stimulates aberrant B-cell maturation, leading to the emergence of self-reactive B cells, which locally produce autoantibodies, in a germinal centre-like structure (GC-like), which is also the location of lymphomagenesis (origin of lymphoma). […] Dysregulation of apoptosis (programmed cell death) is believed to play a role in the pathogenesis of a variety of autoimmune diseases, though its role in Sjgren’s disease is controversial.

• #64 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  Both the Fas and Fas ligand proteins are overexpressed in primary Sjgren’s patients, while expression of BCL-1, which is known to downregulate apoptosis, was found significantly reduced in acinar and ductal epithelial cells of Sjgren’s patients compared to healthy people. […] In situ studies did not show increased apoptosis among glandular epithelial cells but did show reduced apoptosis among infiltrating mononuclear cells. […] Reduced apoptosis was also implicated in the accumulation of autoreactive B-cells found in the glands. […] The relationship of autoantibodies expressed in Sjgren’s syndrome with apoptosis is still being researched. […] Sex hormones seem to influence humoral and cell-mediated immune response, with estrogen being considered one of the biggest factors responsible for sex-immunologic dimorphism. […] Estrogen deficiency appears to play a role in the development of Sjgren’s disease.

• #65 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  Both the Fas and Fas ligand proteins are overexpressed in primary Sjgren’s patients, while expression of BCL-1, which is known to downregulate apoptosis, was found significantly reduced in acinar and ductal epithelial cells of Sjgren’s patients compared to healthy people. […] In situ studies did not show increased apoptosis among glandular epithelial cells but did show reduced apoptosis among infiltrating mononuclear cells. […] Reduced apoptosis was also implicated in the accumulation of autoreactive B-cells found in the glands. […] The relationship of autoantibodies expressed in Sjgren’s syndrome with apoptosis is still being researched. […] Sex hormones seem to influence humoral and cell-mediated immune response, with estrogen being considered one of the biggest factors responsible for sex-immunologic dimorphism. […] Estrogen deficiency appears to play a role in the development of Sjgren’s disease.

• #66 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  Both the Fas and Fas ligand proteins are overexpressed in primary Sjgren’s patients, while expression of BCL-1, which is known to downregulate apoptosis, was found significantly reduced in acinar and ductal epithelial cells of Sjgren’s patients compared to healthy people. […] In situ studies did not show increased apoptosis among glandular epithelial cells but did show reduced apoptosis among infiltrating mononuclear cells. […] Reduced apoptosis was also implicated in the accumulation of autoreactive B-cells found in the glands. […] The relationship of autoantibodies expressed in Sjgren’s syndrome with apoptosis is still being researched. […] Sex hormones seem to influence humoral and cell-mediated immune response, with estrogen being considered one of the biggest factors responsible for sex-immunologic dimorphism. […] Estrogen deficiency appears to play a role in the development of Sjgren’s disease.

• #67 Sjogren Syndrome: Practice Essentials, Etiology, Epidemiology

  https://emedicine.medscape.com/article/332125-overview

  The fact that primary Sjgren syndrome occurs predominantly in women suggests that sex hormones may influence the immunologic manifestations of the disease. The prevalence of serologic markers tends to be lower in male patients than in female patients. Although the role of sex hormones (eg, estrogens, androgens) in the pathogenesis of primary Sjgren syndrome remains unknown, adrenal and gonadal steroid hormone deficiency probably affects immune function.

• #68 Sjogren Syndrome: Practice Essentials, Etiology, Epidemiology

  https://emedicine.medscape.com/article/332125-overview

  The fact that primary Sjgren syndrome occurs predominantly in women suggests that sex hormones may influence the immunologic manifestations of the disease. The prevalence of serologic markers tends to be lower in male patients than in female patients. Although the role of sex hormones (eg, estrogens, androgens) in the pathogenesis of primary Sjgren syndrome remains unknown, adrenal and gonadal steroid hormone deficiency probably affects immune function.

• #69 Sjogren Syndrome: Practice Essentials, Etiology, Epidemiology

  https://emedicine.medscape.com/article/332125-overview

  The fact that primary Sjgren syndrome occurs predominantly in women suggests that sex hormones may influence the immunologic manifestations of the disease. The prevalence of serologic markers tends to be lower in male patients than in female patients. Although the role of sex hormones (eg, estrogens, androgens) in the pathogenesis of primary Sjgren syndrome remains unknown, adrenal and gonadal steroid hormone deficiency probably affects immune function.

• #70 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  Both the Fas and Fas ligand proteins are overexpressed in primary Sjgren’s patients, while expression of BCL-1, which is known to downregulate apoptosis, was found significantly reduced in acinar and ductal epithelial cells of Sjgren’s patients compared to healthy people. […] In situ studies did not show increased apoptosis among glandular epithelial cells but did show reduced apoptosis among infiltrating mononuclear cells. […] Reduced apoptosis was also implicated in the accumulation of autoreactive B-cells found in the glands. […] The relationship of autoantibodies expressed in Sjgren’s syndrome with apoptosis is still being researched. […] Sex hormones seem to influence humoral and cell-mediated immune response, with estrogen being considered one of the biggest factors responsible for sex-immunologic dimorphism. […] Estrogen deficiency appears to play a role in the development of Sjgren’s disease.

• #71 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  Both the Fas and Fas ligand proteins are overexpressed in primary Sjgren’s patients, while expression of BCL-1, which is known to downregulate apoptosis, was found significantly reduced in acinar and ductal epithelial cells of Sjgren’s patients compared to healthy people. […] In situ studies did not show increased apoptosis among glandular epithelial cells but did show reduced apoptosis among infiltrating mononuclear cells. […] Reduced apoptosis was also implicated in the accumulation of autoreactive B-cells found in the glands. […] The relationship of autoantibodies expressed in Sjgren’s syndrome with apoptosis is still being researched. […] Sex hormones seem to influence humoral and cell-mediated immune response, with estrogen being considered one of the biggest factors responsible for sex-immunologic dimorphism. […] Estrogen deficiency appears to play a role in the development of Sjgren’s disease.

• #72 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  Enhanced activity of the type-1 IFN system has been linked to multiple autoimmune diseases, including Sjgren’s syndrome. […] The presence of IFN signature was confirmed in both PBMCs and whole blood in a study that analyzed peripheral blood gene expression profiles in Sjgren’s syndrome. […] One of the cytokines upregulated by IFN is BAFF. […] Autonomic nervous system (ANS) abnormalities are common in Sjgren’s syndrome and may play an etiologic role in its pathogenesis. […] Sjgren’s syndrome mimics several ANS failure syndromes. […] Antimuscarinic acetylcholine receptor autoantibodies, or antibodies interfering with the other neurotransmitters and their receptors, would provide a link between autoimmunity and exocrine dysfunction in Sjgren’s syndrome. […] Recent discoveries from studies in patients with Sjgren’s syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the ANS. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjgren’s syndrome.

• #73 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  Enhanced activity of the type-1 IFN system has been linked to multiple autoimmune diseases, including Sjgren’s syndrome. […] The presence of IFN signature was confirmed in both PBMCs and whole blood in a study that analyzed peripheral blood gene expression profiles in Sjgren’s syndrome. […] One of the cytokines upregulated by IFN is BAFF. […] Autonomic nervous system (ANS) abnormalities are common in Sjgren’s syndrome and may play an etiologic role in its pathogenesis. […] Sjgren’s syndrome mimics several ANS failure syndromes. […] Antimuscarinic acetylcholine receptor autoantibodies, or antibodies interfering with the other neurotransmitters and their receptors, would provide a link between autoimmunity and exocrine dysfunction in Sjgren’s syndrome. […] Recent discoveries from studies in patients with Sjgren’s syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the ANS. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjgren’s syndrome.

• #74 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  Enhanced activity of the type-1 IFN system has been linked to multiple autoimmune diseases, including Sjgren’s syndrome. […] The presence of IFN signature was confirmed in both PBMCs and whole blood in a study that analyzed peripheral blood gene expression profiles in Sjgren’s syndrome. […] One of the cytokines upregulated by IFN is BAFF. […] Autonomic nervous system (ANS) abnormalities are common in Sjgren’s syndrome and may play an etiologic role in its pathogenesis. […] Sjgren’s syndrome mimics several ANS failure syndromes. […] Antimuscarinic acetylcholine receptor autoantibodies, or antibodies interfering with the other neurotransmitters and their receptors, would provide a link between autoimmunity and exocrine dysfunction in Sjgren’s syndrome. […] Recent discoveries from studies in patients with Sjgren’s syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the ANS. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjgren’s syndrome.

• #75 Dry Eye in Sjogren’s Syndrome – EyeWiki

  https://eyewiki.org/Dry_Eye_in_Sjogren%27s_Syndrome

  The genomic search for critical genes is difficult as a result of the multigenic pattern of inheritance and the strong role of undefined environmental factors. […] These results emphasize the importance of immune factors, such as cytokines, matrix metalloproteases, and autoantibodies, in decreasing neurosecretory circuits and inducing glandular dysfunction. An antibody against muscarinic M3 receptor has been implicated leading to the development of orally administered agonists of the M3 receptor.

• #76 Advances in understanding the pathogenesis of primary Sjögren’s syndrome | Nature Reviews RheumatologyClose bannerClose banner

  https://www.nature.com/articles/nrrheum.2013.110

  IL-12 production and subsequent T-cell activation, mainly IFN-γ-secreting type 1 T-helper cells, have also been implicated in disease pathogenesis. […] Furthermore, evidence implicates neuroendocrine system dysfunction in pSS pathogenesis. […] Environmental triggers promote activation of the innate immune system and the production of interferons (IFNs), which, in susceptible individuals, represent the first stages of primary Sjögren’s syndrome (pSS) pathogenesis. […] B-cell-activating factor is induced by type I and type II IFNs and has a key role in activating autoreactive B cells; other cytokines such IL-21 could also be important for this process. […] Continuous B-cell activation as a result of the autoimmune response and subtle deficiencies in the control of nuclear factor κB activation might underlie increased lymphomagenesis associated with pSS.

• #77

  https://link.springer.com/article/10.1007/s10238-021-00728-6

  Interestingly, some authors found a correlation between EBV presence, disease severity and extra-glandular manifestations. […] Genetic factors are supposed to play an important role in SS pathogenesis. […] Familial association studies showed that about one-third of SS patients have a relative with another connective tissue disease. […] More recently, associations between certain Human Leukocyte Antigen (HLA) alleles (e.g., HLA DRB1*03:01, DQA1*05:01, DQB1*02:01) and SS susceptibility have been demonstrated by genomic studies. […] It is widely accepted that epigenetic factors play an important role in autoimmune disorders. […] Nowadays, epithelial cells are considered major players in the pathogenesis of SS, so that the term autoimmune „epithelitis” is increasingly used to describe this condition.

• #78 Sjögren’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Sj%C3%B6gren%27s_disease

  This study included data from a discovery cohort of 395 patients of European ancestry with primary Sjgren’s disease, and 1,975 healthy control individuals, and from a replication study that comprised 1,234 cases and 4,779 healthy controls. […] Associations with polymorphisms located at six independent loci were also detected; IRF5, STAT4, BLK, IL12A, TNIP1, and CXCR5. […] This also suggested the activation of the innate immune system, notably through the IFN system, B-cell activation through CXCR5-directed recruitment to lymphoid follicles and B-cell receptor (BCR) activation involving BLK, and T-cell activation owing to HLA susceptibility and the IL-12-IFN–axis. […] Beyond genetics, epigenetic abnormality related to DNA methylation, histone acetylation, or microRNA expression probably has a key role in the pathogenesis of autoimmune diseases, including Sjgren’s disease, though research in this area is very limited.

• #79 Primary Sjögren’s syndrome: new perspectives on salivary gland epithelial cells | European Journal of Medical Research | Full Text

  https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-01967-5

  In SGECs from pSS patients, there is an overall decrease in DNA methylation level, contrasting with unaffected levels in T and B cells. […] Consequently, SGEC dysfunction may partly result from altered DNA methylation level. […] The SG possesses a delicate structure that often faces disorder or even destruction in pSS patients. […] Evidence demonstrates that SGECs undergo considerable structural changes in their apical, lateral and basal structure as well as in the ECM, causing loss of barrier function and cell polarity, consequently resulting in dysfunction. […] Inadequate salivation is the culprit of xerostomia in pSS. Extensive research has been conducted over the decades to examine both fluid and protein secretion. […] The deviations may take place in the activation of muscarinic receptor, Ca2+ signaling, and apical channels.

• #80 Primary Sjögren’s syndrome: new perspectives on salivary gland epithelial cells | European Journal of Medical Research | Full Text

  https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-01967-5

  In SGECs from pSS patients, there is an overall decrease in DNA methylation level, contrasting with unaffected levels in T and B cells. […] Consequently, SGEC dysfunction may partly result from altered DNA methylation level. […] The SG possesses a delicate structure that often faces disorder or even destruction in pSS patients. […] Evidence demonstrates that SGECs undergo considerable structural changes in their apical, lateral and basal structure as well as in the ECM, causing loss of barrier function and cell polarity, consequently resulting in dysfunction. […] Inadequate salivation is the culprit of xerostomia in pSS. Extensive research has been conducted over the decades to examine both fluid and protein secretion. […] The deviations may take place in the activation of muscarinic receptor, Ca2+ signaling, and apical channels.

• #81 :: JCN :: Journal of Clinical Neurology

  https://www.thejcn.com/DOIx.php?id=10.3988/jcn.2018.14.4.588

  Sjogren’s syndrome is characterized by the involvement of exocrine glands, predominantly the salivary and lacrimal glands. […] Small-vessel vasculitis has often been postulated as a pathogenic mechanism of the CNS involvement in Sjogren’s syndrome, but the involvement of major cerebral vessels in Sjogren’s syndrome has only rarely been reported. […] Vasculitis is one of the mechanisms underlying CNS involvement in primary Sjogren’s syndrome. […] Large-artery involvement in Sjogren’s syndrome is rare, with only three cases reported in the literature. […] Our case highlights the presence of vasculitic involvement of the large cerebral vessels in primary Sjogren’s syndrome, which can be confirmed by HRVWI.

• #82 :: JCN :: Journal of Clinical Neurology

  https://www.thejcn.com/DOIx.php?id=10.3988/jcn.2018.14.4.588

  Sjogren’s syndrome is characterized by the involvement of exocrine glands, predominantly the salivary and lacrimal glands. […] Small-vessel vasculitis has often been postulated as a pathogenic mechanism of the CNS involvement in Sjogren’s syndrome, but the involvement of major cerebral vessels in Sjogren’s syndrome has only rarely been reported. […] Vasculitis is one of the mechanisms underlying CNS involvement in primary Sjogren’s syndrome. […] Large-artery involvement in Sjogren’s syndrome is rare, with only three cases reported in the literature. […] Our case highlights the presence of vasculitic involvement of the large cerebral vessels in primary Sjogren’s syndrome, which can be confirmed by HRVWI.

• #83 :: JCN :: Journal of Clinical Neurology

  https://www.thejcn.com/DOIx.php?id=10.3988/jcn.2018.14.4.588

  Sjogren’s syndrome is characterized by the involvement of exocrine glands, predominantly the salivary and lacrimal glands. […] Small-vessel vasculitis has often been postulated as a pathogenic mechanism of the CNS involvement in Sjogren’s syndrome, but the involvement of major cerebral vessels in Sjogren’s syndrome has only rarely been reported. […] Vasculitis is one of the mechanisms underlying CNS involvement in primary Sjogren’s syndrome. […] Large-artery involvement in Sjogren’s syndrome is rare, with only three cases reported in the literature. […] Our case highlights the presence of vasculitic involvement of the large cerebral vessels in primary Sjogren’s syndrome, which can be confirmed by HRVWI.

• #84 Sjogren’s Syndrome – Rheumatology Advisor

  https://www.rheumatologyadvisor.com/ddi/sjogrens-syndrome/

  Patients with primary Sjgrens syndrome are at a 14-fold increased risk of developing lymphomas, particularly B-cell lymphoma, compared with patients without Sjgrens syndrome. […] Increased use of biologic therapies in Sjgrens syndrome is based on an improved understanding of the mechanism of Sjgrens syndrome and the establishment of therapeutic targets for these agents in patients with other autoimmune disorders. […] Rituximab is a chimeric anti-CD20 monoclonal antibody that depletes B cells by causing a direct toxic effect on these cells over a period of 4 to 12 months. Rituximab treatment has been found to be effective for patients with primary Sjogrens syndrome. […] The monoclonal anti-BAFF antibody belimumab was shown to be effective in the treatment of Sjgrens syndrome in a prospective 1-year open-label bicentric study involving 30 patients.

• #85 B cells in the pathogenesis of primary Sjögren syndrome | Nature Reviews RheumatologyClose bannerClose banner

  https://www.nature.com/articles/nrrheum.2018.1

  Genetic risk factors associated with primary Sjögren syndrome (pSS) can promote B cell activation, as can epigenetic changes, which can sometimes affect the same disease-associated genes. […] BAFF (also known as TNF ligand superfamily member 13B) is central to the crosstalk between early activation of the innate immune system and the stimulation of autoreactive B cells. […] CD27+ memory B cells, marginal zone B cells, plasmablasts and plasma cells are the key subsets of B cells involved in the pathogenesis of pSS. […] Target organs (salivary and lachrymal glands) are involved in B cell activation, notably via the formation of germinal centre-like structures within the epithelium and plasma cell niches. […] Continuous stimulation of autoreactive B cells by immune complexes is the first step towards lymphomagenesis associated with pSS.

• #86 B cells in the pathogenesis of primary Sjögren syndrome | Nature Reviews RheumatologyClose bannerClose banner

  https://www.nature.com/articles/nrrheum.2018.1

  Continuously activated autoreactive B cells need to be tightly controlled by genetic factors and by the tissue microenvironment as subtle defects in these controls might promote clonal escape and lymphomagenesis. […] The involvement of B cells in the pathogenesis of pSS has long been suspected on the basis of clinical observations that include the presence of serum autoantibodies, hypergammaglobulinaemia, increased levels of free light chains and increased risk of B cell lymphoma. […] Moreover, the composition of the B cell subset is altered in pSS. […] In this Review, we discuss the mechanisms that support the increased activation of B cells in pSS, including genetic and epigenetic factors and environmental triggers that promote B cell activation via the innate immune system. […] An important role also exists for the target tissue (exocrine glands, namely the salivary and lachrymal glands), which promotes local B cell activation.

• #87 Advances in understanding the pathogenesis of primary Sjögren’s syndrome | Nature Reviews RheumatologyClose bannerClose banner

  https://www.nature.com/articles/nrrheum.2013.110

  IL-12 production and subsequent T-cell activation, mainly IFN-γ-secreting type 1 T-helper cells, have also been implicated in disease pathogenesis. […] Furthermore, evidence implicates neuroendocrine system dysfunction in pSS pathogenesis. […] Environmental triggers promote activation of the innate immune system and the production of interferons (IFNs), which, in susceptible individuals, represent the first stages of primary Sjögren’s syndrome (pSS) pathogenesis. […] B-cell-activating factor is induced by type I and type II IFNs and has a key role in activating autoreactive B cells; other cytokines such IL-21 could also be important for this process. […] Continuous B-cell activation as a result of the autoimmune response and subtle deficiencies in the control of nuclear factor κB activation might underlie increased lymphomagenesis associated with pSS.

• #88 Pathogenesis of Sjögren’s disease – UpToDate

  https://www.uptodate.com/contents/pathogenesis-of-sjogrens-disease

  Pathogenesis of Sjögren’s disease […] The pathogenesis of SjD is thought to be a multistep process, triggered by an environmental factor, most likely viral, in a genetically predisposed individual. An immune response involving innate and adaptive immunity, leading to autoimmunity and chronic inflammation, are central components of the disease process. […] The pathogenesis of SjD is typically modeled as a multistep process, triggered by an environmental factor, most likely viral, in a genetically predisposed individual. The initial events engage the innate immune system, but propagation and perpetuation of the autoimmune process require a continual interplay between the innate and adaptive immune systems. […] The result is autoreactive B-cell stimulation, autoantibody production, and chronic inflammation of the salivary and lacrimal glands and other tissues. Extraglandular manifestations may arise from autoimmune exocrinopathy akin to that in the salivary glands (eg, interstitial nephritis, biliary cholangitis), immune-complex deposition (eg, cryoglobulinemic vasculitis), and extranodal lymphoproliferation (eg, lymphocytic interstitial pneumonitis). Chronic stimulation of B cells in the target tissue may promote lymphomagenesis, again through a multistep process in a genetically susceptible individual.

• #89 Pathogenesis of Vaginal Dryness in Primary Sjögren’s Syndrome: A Histopathological Case-control Study – ACR Meeting Abstracts

  https://acrabstracts.org/abstract/pathogenesis-of-vaginal-dryness-in-primary-sjogrens-syndrome-a-histopathological-case-control-study/

  Women with primary Sjgrens syndrome (pSS) often experience vaginal dryness, but the pathogenesis of this symptom is unknown. […] In the current analysis, we quantitatively studied changes in lymphocyte subsets, endothelial cells and soluble immune markers in the vagina and endocervix of women with pSS, compared to age-matched controls, which may explain vaginal dryness. […] Our findings indicate that in addition to chronic inflammation, vascular disturbances in the vaginal mucosa are likely to contribute to vaginal dryness in women with pSS.

• #90 Pathogenesis of Vaginal Dryness in Primary Sjögren’s Syndrome: A Histopathological Case-control Study – ACR Meeting Abstracts

  https://acrabstracts.org/abstract/pathogenesis-of-vaginal-dryness-in-primary-sjogrens-syndrome-a-histopathological-case-control-study/

  Women with primary Sjgrens syndrome (pSS) often experience vaginal dryness, but the pathogenesis of this symptom is unknown. […] In the current analysis, we quantitatively studied changes in lymphocyte subsets, endothelial cells and soluble immune markers in the vagina and endocervix of women with pSS, compared to age-matched controls, which may explain vaginal dryness. […] Our findings indicate that in addition to chronic inflammation, vascular disturbances in the vaginal mucosa are likely to contribute to vaginal dryness in women with pSS.

• #91 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  Enhanced activity of the type-1 IFN system has been linked to multiple autoimmune diseases, including Sjgren’s syndrome. […] The presence of IFN signature was confirmed in both PBMCs and whole blood in a study that analyzed peripheral blood gene expression profiles in Sjgren’s syndrome. […] One of the cytokines upregulated by IFN is BAFF. […] Autonomic nervous system (ANS) abnormalities are common in Sjgren’s syndrome and may play an etiologic role in its pathogenesis. […] Sjgren’s syndrome mimics several ANS failure syndromes. […] Antimuscarinic acetylcholine receptor autoantibodies, or antibodies interfering with the other neurotransmitters and their receptors, would provide a link between autoimmunity and exocrine dysfunction in Sjgren’s syndrome. […] Recent discoveries from studies in patients with Sjgren’s syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the ANS. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjgren’s syndrome.

• #92 Pathogenesis of Sjögren’s syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2766246/

  Enhanced activity of the type-1 IFN system has been linked to multiple autoimmune diseases, including Sjgren’s syndrome. […] The presence of IFN signature was confirmed in both PBMCs and whole blood in a study that analyzed peripheral blood gene expression profiles in Sjgren’s syndrome. […] One of the cytokines upregulated by IFN is BAFF. […] Autonomic nervous system (ANS) abnormalities are common in Sjgren’s syndrome and may play an etiologic role in its pathogenesis. […] Sjgren’s syndrome mimics several ANS failure syndromes. […] Antimuscarinic acetylcholine receptor autoantibodies, or antibodies interfering with the other neurotransmitters and their receptors, would provide a link between autoimmunity and exocrine dysfunction in Sjgren’s syndrome. […] Recent discoveries from studies in patients with Sjgren’s syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the ANS. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjgren’s syndrome.

• #93 Pathogenesis of Sjogren’s syndrome | Health & Environmental Research Online (HERO) | US EPA

  https://hero.epa.gov/hero/index.cfm/reference/details/reference_id/505701

  Nonimmune mechanisms that may contribute to exocrine dysfunction include local and systemic androgen deficiency and autonomic nervous system dysfunction. […] Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjogren’s syndrome.

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