How stress contributes to autoimmunity—lessons from Sjögren's syndrome

Skopouli, Fotini N.; Katsiougiannis, Stergios

doi:10.1002/1873-3468.12933

Cited by 41 publications

(28 citation statements)

References 77 publications

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“…The therapeutic approach to oral dryness should be driven by the baseline measurement of salivary glandular function, and not by the patient’s subjective feelings, since environmental and personal stressing factors may influence the subjective feeling of dryness,29 which often does not match with the objective measurement of glandular function. We recommend the baseline evaluation of salivary glandular function by measuring whole salivary flows before starting therapeutic interventions, always ruling out SjS-unrelated conditions (ie, candidiasis, burning mouth syndrome); salivary scintigraphy may also be considered 30.…”

Section: Resultsmentioning

confidence: 99%

EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies

et al. 2019

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The therapeutic management of Sjögren syndrome (SjS) has not changed substantially in recent decades: treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. In view of this scenario, the European League Against Rheumatism (EULAR) promoted and supported an international collaborative study (EULAR SS Task Force) aimed at developing the first EULAR evidence and consensus-based recommendations for the management of patients with SjS with topical and systemic medications. The aim was to develop a rational therapeutic approach to SjS patients useful for healthcare professionals, physicians undergoing specialist training, medical students, the pharmaceutical industry and drug regulatory organisations following the 2014 EULAR standardised operating procedures. The Task Force (TF) included specialists in rheumatology, internal medicine, oral health, ophthalmology, gynaecology, dermatology and epidemiology, statisticians, general practitioners, nurses and patient representatives from 30 countries of the 5 continents. Evidence was collected from studies including primary SjS patients fulfilling the 2002/2016 criteria; when no evidence was available, evidence from studies including associated SjS or patients fulfilling previous sets of criteria was considered and extrapolated. The TF endorsed the presentation of general principles for the management of patients with SjS as three overarching, general consensus-based recommendations and 12 specific recommendations that form a logical sequence, starting with the management of the central triplet of symptoms (dryness, fatigue and pain) followed by the management of systemic disease. The recommendations address the use of topical oral (saliva substitutes) and ocular (artificial tear drops, topical non-steroidal anti-inflammatory drugs, topical corticosteroids, topical CyA, serum tear drops) therapies, oral muscarinic agonists (pilocarpine, cevimeline), hydroxychloroquine, oral glucocorticoids, synthetic immunosuppressive agents (cyclophosphamide, azathioprine, methotrexate, leflunomide and mycophenolate), and biological therapies (rituximab, abatacept and belimumab). For each recommendation, levels of evidence (mostly modest) and TF agreement (mostly very high) are provided. The 2019 EULAR recommendations are based on the evidence collected in the last 16 years in the management of primary 2002 SjS patients and on discussions between a large and broadly international TF. The recommendations synthesise current thinking on SjS treatment in a set of overarching principles and recommendations. We hope that the current recommendations will be broadly applied in clinical practice and/or serve as a template for national societies to develop local recommendations.

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Section: Resultsmentioning

confidence: 99%

EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies

et al. 2019

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“…With the increasing awareness of autoantibody-positive cases, autoimmune encephalitis has received increasing attention (Dubey et al 2018). This autoimmune disease is related to genetic susceptibility, infection, and stressful life events, and is caused by excessive self-response and antigen-driven immune responses (David et al 2018;Karagianni et al 2019;Skopouli and Katsiougiannis 2018). In patients with SARS, autoantibodies against the coronavirus spike protein were found to react with human epithelial cells and endothelial cells, and cause cytotoxicity Yang et al 2005).…”

Section: Possible Mechanisms Of Neurological Symptomsmentioning

confidence: 99%

Involvement of the Nervous System in SARS-CoV-2 Infection

2020

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As a severe and highly contagious infectious disease, coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several case reports have demonstrated that the respiratory system is the main target in patients with COVID-19, but the disease is not limited to the respiratory system. Case analysis indicated that the nervous system can be invaded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that 36.4% of COVID-19 patients had neurological symptoms. Importantly, the involvement of the CNS may be associated with poor prognosis and disease worsening. Here, we discussed the symptoms and evidence of nervous system involvement (directly and indirectly) caused by SARS-CoV-2 infection and possible mechanisms. CNS symptoms could be a potential indicator of poor prognosis; therefore, the prevention and treatment of CNS symptoms are also crucial for the recovery of COVID-19 patients.

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“…Genetic, hormonal and environmental factors seem to play a role in the development of diseases. Physical and emotional stresses are the main environmental factors in etiology of autoimmune diseases [16]. The two main hormonal pathways that are activated in response to stress alone or together are the Hypothalamicpituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS).…”

Section: Discussionmentioning

confidence: 99%

“…This phenomenon, if chronic, leads to less secretion units in the salivary glands, resulting in reduced saliva production. During apoptosis, the production of inflammatory cytokines, such as IL-6 and type-1 IFNs, and the release and secretion of endogenous antigens and chaperon proteins via apoptotic buds of salivary cells can even be involved in the pathogenesis of OLP [16].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have also shown the contradictory effects of adrenergic agonist and antagonist drugs on the salivary flow rate [27][28][29]. Also lowering entrance of sympathetic nerve fibers to the parotid gland in comparison with other major salivary glands that cause to less expression of adrenergic receptors on the surface of the secretory cells of parotid gland [13], stimulation of saliva secretion through chewing instead of taste triggers that cause to preferably stimulation of PNS to SNS and more time opportunity for the exchange of acinar cells and ducts in unstimulated saliva to stimulated saliva [10,16] justify lower levels of adrenergic receptors in the stimulated saliva compared to the unstimulated saliva in both control and OLP groups. Upregulation of salivary adrenergic receptor in OLP patients, probably source both receptors in the secretory cells of salivary gland and elevated level of these receptors in blood cells.…”

Section: Discussionmentioning

confidence: 99%

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Full Upregulation of α1 and β1 adrenergic receptors as an effective factor on hyposalivation of patients with OLP

Gholizadeh¹,

Rezayi²,

Sheykhbahaei³

2019

Preprint

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Objectives: Oral lichen planus (OLP) is one of the common chronic, autoimmune disorders in oral cavity. Regarding the role of adrenergic receptors in mediating stress and that’s effect on salivary composition, the purpose of this study was to investigate salivary levels of α1- and β1-adrenergic receptors in OLP patients to response to this research question: Do agonist or antagonist of adrenergic receptors affect hyposalivation of OLP patients? Method: In this case-control study, stimulated and unstimulated saliva samples were collected from 33 patients and 33 healthy individuals. The salivary flow rate and levels of α1- and β1-adrenergic receptors were measured by ELISA assay. Data were analyzed using SPSS 25 and T-test. Results: The stimulated and unstimulated salivary flow rate was significantly lower in OLP patients than healthy subjects. The α1-adrenergic receptors in the unstimulated saliva of patients was significantly higher than in the healthy subjects (p<0.001). α1-receptor in unstimulated saliva in both groups of patients (p<0.001) and healthy subjects (p=0.006) was significantly higher than stimulated saliva in the same groups. The level of β1-adrenergic receptors in the patients was significantly higher in the unstimulated saliva (p=0.001) and lower in the stimulated saliva than in the healthy subjects (p=0.003). β1-receptor was significantly higher in the unstimulated saliva than stimulated saliva in the patients (p<0.001). Conclusion: high levels of α1- and β1-adrenergic receptors in saliva of OLP patients reduce salivary flow rate by increasing the salivary proteins, mucin and saliva viscosity. Selective antagonist of α1- and β1-adrenergic receptors Can improve hyposalivation of OLP patients. Keywords: Lichen Planus, Oral, Adrenergic Receptors, Adrenoceptors, saliva

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How stress contributes to autoimmunity—lessons from Sjögren's syndrome

Cited by 41 publications

References 77 publications

EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies

EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies

Involvement of the Nervous System in SARS-CoV-2 Infection

Full Upregulation of α1 and β1 adrenergic receptors as an effective factor on hyposalivation of patients with OLP

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