The Involvement of Alarmins in the Pathogenesis of Sjögren's Syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disease that affects exocrine glands, primarily the salivary and lachrymal glands. It is characterized by lymphoplasmacytic infiltration of the glandular tissues, ultimately leading to their dysfunction and destruction. Besides classic dry eyes and dry mouth defined as sicca syndrome, patients affected by the disease also typically display symptoms such as fatigue, pain and in more than 50% of cases, systemic manifestations such as arthritis, interstitial lung involvement, neurological involvement and an increased risk of lymphoma. The pathophysiological mechanisms underlying SS still remain elusive. The crucial role of innate immunity has been advocated in recent years regarding the pathogenesis of pSS, especially in the initiation and progression toward autoimmunity. Alarmins are endogenous molecules that belong to the large family of damage associated molecular pattern (DAMP). Alarmins are rapidly released, ensuing cell injury and interacting with pattern recognition receptors (PRR) such as toll-like receptors (TLR) to recruit and activate cells of the innate immune system and to promote adaptive immunity responses. This review highlights the current knowledge of various alarmins and their role in the pathogenesis of pSS.

Addressing the clinical unmet needs in primary Sjögren's Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts.

For many decades, the clinical unmet needs of primary Sjögren's Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs.

Current State of Knowledge on Primary Sjögren's Syndrome, an Autoimmune Exocrinopathy.

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune rheumatic disease characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands, whereby sicca syndrome and/or systemic manifestations are the clinical hallmarks, associated with a particular autoantibody profile. pSS is the most frequent connective tissue disease after rheumatoid arthritis, affecting 0.3-3% of the population. Women are more prone to develop pSS than men, with a sex ratio of 9:1. Considered in the past as innocent collateral passive victims of autoimmunity, the epithelial cells of the salivary glands are now known to play an active role in the pathogenesis of the disease. The aetiology of the "autoimmune epithelitis" still remains unknown, but certainly involves genetic, environmental and hormonal factors. Later during the disease evolution, the subsequent chronic activation of B cells can lead to the development of systemic manifestations or non-Hodgkin's lymphoma. The aim of the present comprehensive review is to provide the current state of knowledge on pSS. The review addresses the clinical manifestations and complications of the disease, the diagnostic workup, the pathogenic mechanisms and the therapeutic approaches.

Impact of tobacco smoking upon disease risk, activity and therapeutic response in systemic lupus erythematosus: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course and prognosis. Published studies present conflicting data regarding the impact of cigarette smoking on SLE risk, disease activity, clinical manifestations and treatment response. We performed a comprehensive literature search using Medline, EMBASE and the Cochrane Collaboration database, and hand searches of relevant bibliographies. All original studies investigating the relationship between smoking and SLE were included in TABALUP. Two investigators systematically extracted data from the relevant studies. When possible, meta-analyses were performed. The meta-analysis of 9 case-controls studies show an increased risk of SLE in current-smokers compared to never-smokers (OR: 1.49 [95%CI: 1.06-2.08]), while former-smokers were not at increased risk of SLE. Data on passive smoking remains scarce and controversial. Pooled analysis studies did not find an over-risk of anti-dsDNA, anti-Sm or anti-SSA positivity according to smoking status. Tobacco smoking significantly reduced the therapeutic effectiveness of hydroxychloroquine in cutaneous lesions (pooled OR 0.53; 95%CI: 0.305-0.927) and belimumab in systemic manifestations (HR 0.10; 95% CI 0.02-0.43). In addition to its usual adverse effects, cigarette smoking is a risk factor of SLE and negatively influences the course of the disease and its treatment. We believe that smoking cessation should be one of the main target of physicians treating SLE patients.