Search Results (522)

Background: Wheat or cow’s milk intake might influence the primary Sjögren’s Syndrome (pSS) clinical manifestations. A high prevalence (20–30%) of autoimmune diseases, including pSS, has been reported in non-celiac wheat sensitivity (NCWS). This study aimed to identify the prevalence of self-reported NCWS and sensitivity/intolerance to other foods in patients with pSS, and to establish the specific clinical and immunological features of this subgroup of patients. Methods: 82 prospectively enrolled pSS patients were compared to 161 type 2 diabetes controls without rheumatological disease. The presence of a self-reported NCWS, and/or self-reported milk intolerance (SRMI), and/or multiple food sensitivity (MFS) was assessed by a validated questionnaire. Clinical and immunological features of pSS subjects, stratified according to the presence/absence of self-reported NCWS, were analyzed. Results: pSS patients had a higher frequency of self-reported NCWS (47.6% vs. 18.6%, p < 0.0001), SRMI (29.3% vs. 5.6%, p < 0.0001) and MFS (30.5% vs. 9.3% p < 0.0003) compared to controls. After the intake of wheat-containing products, 18 (21.9%) pSS patients reported the worsening of disease-specific symptoms, whereas 11 (13.4%) reported a significative clinical improvement after wheat-free diet (WFD) introduction. Moreover, 47.6% of pSS subjects complained of wheat-related gastrointestinal/extraintestinal disorders. No clinical/immunological feature differentiates pSS patients with and without self-reported NCWS, excluding a higher frequency of SRMI (39.5% vs. 11.9%, p = 0.01) and MFS (65.7% vs. 23.8%; p = 0.0004) in the former. Conclusions: This study shows a clear association between pSS and NCWS, confirming that wheat intake could be a common trigger of symptoms of both these conditions. WFD adoption seems to reduce both gastrointestinal/extraintestinal and pSS-specific symptoms in a subgroup of pSS patients, opening new possibilities for their clinical management. Full article

Background/Objectives: Black hairy tongue syndrome (BHT) is characterized by structural epithelial changes and a dark discoloration on the surface of the tongue, causing a variety of symptoms such as xerostomia, altered taste, and nausea. Methods: Herein, we report a 70-year-old female patient with a history of Sjogren’s syndrome, rheumatoid arthritis, and occasional use of intranasal and inhaled corticosteroids, who presented with BHT exacerbated by consumption of colored beverages and carbohydrates. We also provide a review of the literature on published articles reporting cases of BHT syndrome. Results: Our patient’s condition improved after implementing dietary restrictions in combination with local care. A literature review revealed that the most common reported exposures and underlying conditions in patients with BHT were the recent administration of antibiotics, solid organ or hematologic malignancy, immunosuppressants, smoking, corticosteroids, autoimmune conditions, receipt of antidepressants, local radiation therapy, proton pump inhibitors, and alcohol. The majority of cases were successfully managed with the elimination of implicated factors when possible and local hygiene. Conclusions: Different factors may contribute to the development of BHT. Discontinuation of implicated medications together with measures for topical care constitute the most effective ways to achieve resolution. Full article

Autoimmune diseases are characterized by immune response dysregulation against self-components, leading to chronic inflammation and tissue damage. Vitamin C (VitC), a water-soluble vitamin with established functions in antioxidant defence and collagen synthesis, has also been of interest based on its potential immunomodulatory effects. This review discusses the role of VitC in the course and progression of (A) autoimmune diseases (multiple sclerosis, rheumatoid arthritis, Sjögren’s disease, type 1 diabetes, Hashimoto’s thyroiditis, pernicious anaemia, antiphospholipid syndrome), (B) other immune-mediated diseases (Crohn’s disease, periodontitis), and (C) Alzheimer’s disease, a neurodegenerative disorder with autoimmune features. Results from clinical, observational, and experimental trials show that VitC deficiency is common in many of these diseases and may contribute to increased oxidative stress and immune disequilibrium. Supplementation has been associated with improved antioxidant levels, control of inflammatory mediators, and, in some cases, clinical outcomes like disease activity decrease or symptom load. Although findings vary across conditions and few large, randomized trials are available, the overall evidence indicates that maintaining good VitC status can be useful in maintaining immune homeostasis and reducing inflammation. VitC should be viewed as an adjunct to be employed safely, perhaps and ideally within larger treatment regimens, but not in place of effective therapies. Further research, including large-scale clinical trials, will be required to determine more clearly optimal dosing, timing of treatment, and patient population most likely to benefit. By integration of current knowledge, this review recognizes both promise in VitC for treatment of autoimmune/immune-mediated disease and promise in its potential use within future treatment regimens. Full article

Objectives: Lepidium meyenii Walpers (LMW), a high-altitude plant, is known to stimulate hormone release, counteract neurodegeneration, and protect against oxidative stress. Saliva is vital for oral health, and reduced production leads to xerostomia, often caused by aging, radiation, or Sjögren’s syndrome. Key pathological features include mesenchymal fibrosis and acinar atrophy, largely regulated by the TGF-β1 pathway. Current treatments are limited, with many patients relying on artificial saliva. Developing therapies to restore salivary function could offer significant benefits. Methods: In this study, we assessed the protective effects of LMW extract (LMWE) in irradiated C57BL/6J mice and TGF-β1-treated rat parotid acinar cells (Par-C10) using histological, molecular, bioenergetic, and 3D organoid analyses to evaluate salivary gland regeneration and lineage-specific differentiation. Results: LMWE significantly restored gland weight, shortened secretion lag time, and increased amylase activity in irradiated mice. Histological and molecular analyses showed reduced acinar atrophy and fibrosis, preservation of epithelial polarity, and upregulation of Mist1, AQP5, and amylase. In vitro, LMWE protected Par-C10 cells from TGF-β1-induced senescence, preserved mitochondrial membrane potential, and improved epithelial barrier function. In 3D organoid cultures of Par-C10 cells embedded in matrix, (1E,4Z)-1-(2,4-dihydroxyphenyl)-5-(3,4-dihydroxyphenyl) penta-1,4-dien-3-one (DHPPD) and (Z)-N-phenyldodec-2-enamide (E4Z-PD)-selectively enhanced acinar and ductal lineage differentiation, respectively. Conclusions: These results suggest that LMWE promotes salivary gland regeneration through antioxidative and lineage-specific mechanisms and may represent a safe and effective therapeutic strategy for xerostomia. Full article

Background/Objectives: Dry eye disease (DED) is a prevalent, complex disorder with a major impact on patients’ quality of life. While artificial tears (AT) are still the first-line treatment, their effectiveness is often limited in moderate-to-severe cases. Autologous serum (AS) and platelet-rich plasma (PRP) are now recognized as viable biologic treatments due to their regenerative and anti-inflammatory characteristics. This systematic review and meta-analysis sought to assess and compare the clinical efficacy of PRP, AS, and AT in the treatment of DED, with a focus on comparative studies. Methods: A comprehensive search of PubMed, Scopus, and Google Scholar was conducted until June 2025 for studies directly comparing PRP, AS, and AT. Eligible trials included patients with DED who reported results such as the Schirmer test, tear break-up time (TBUT), and Ocular Surface Disease Index (OSDI). The risk of bias was calculated using ROB 2 for randomized trials and ROBINS-I for non-randomized studies. Meta-analyses were carried out using standardized mean differences (SMDs) and 95% confidence intervals (CIs). Results: Seventeen studies were included in the systematic review. Both PRP and AS demonstrated greater improvements in OSDI, TBUT, and Schirmer test scores compared to AT. PRP showed a trend toward better outcomes than AS, especially in studies using injectable PRP. However, substantial heterogeneity and methodological variability were noted. Conclusions: Comparative research suggests that PRP and AS are more effective than AT in treating DED. Direct comparisons of PRP and AS yield varied results, with the route of delivery impacting outcomes. Given the heterogeneity of current protocols, further standardized, long-term trials are required to confirm the optimal delivery method and ensure safety. Full article

Fibrosis is a pathological process characterized by the excessive accumulation of extracellular matrix (ECM), particularly collagen, leading to tissue scarring, architectural distortion, and organ dysfunction. While fibrosis is a physiological component of wound healing, its persistence and dysregulation can drive chronic tissue damage and organ dysfunction. In autoimmune diseases, fibrosis arises from prolonged inflammation and immune system dysregulation, creating a vicious cycle that exacerbates tissue injury and promotes disease progression. This review provides a comprehensive overview of the fibrotic processes across a range of immune-mediated and autoimmune conditions, including systemic sclerosis (SSc), morphea, autoimmune hepatitis (AIH), systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA), Finally, we discuss current and emerging antifibrotic strategies aimed at interrupting pathological ECM remodeling and restoring tissue homeostasis. Full article

Adropin is a regulatory peptide hormone involved in metabolic homeostasis, cardiovascular protection, and immune modulation. Recent evidence suggests that adropin plays a role in the pathophysiology of autoimmune rheumatic diseases (ARDs) by influencing key processes such as endothelial function, oxidative stress, tissue fibrosis, and immune cell regulation. This review summarizes current knowledge on adropin’s biological functions and its relevance in conditions including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjögren’s syndrome, osteoarthritis, psoriasis, Behçet’s disease, and Kawasaki disease. We discuss how adropin interacts with various signaling pathways and highlight its potential role in macrophage polarization, regulatory T cell activity, and fibrotic remodeling. Although data remain limited and sometimes conflicting, altered adropin levels have been observed across several ARDs, suggesting potential utility as a biomarker or therapeutic target. Further research is needed to clarify its clinical significance and translational potential in immune-mediated diseases. Full article

Autoimmune diseases are characterized by dysregulated adaptive immune responses leading to chronic inflammation and tissue damage. Cytokines and growth factors play central roles in modulating immune regulation, inflammation, and tissue repair, thereby representing critical biomarkers for the enhancement of diagnosis, prognosis, and therapeutic monitoring. This review provides a comprehensive overview of pro-inflammatory and anti-inflammatory cytokines, as well as growth factors, emphasizing their pathogenic roles and clinical relevance across various autoimmune diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and connective tissue diseases such as systemic sclerosis, Sjögren’s syndrome, and systemic lupus erythematosus. Key pro-inflammatory cytokines—such as TNF-α, IL-1β, IL-6, IL-17, and IFN-γ—are examined regarding their contributions to disease progression and activity, alongside anti-inflammatory cytokines like IL-10 and IL-4, which regulate immune tolerance and inflammation resolution. Growth factors, such as TGF-β, are analyzed for their dual roles in immune modulation, fibrosis, and tissue remodeling. Cytokine signature profiles employed as diagnostic tools are discussed, together with the need for assay standardization. Advances in multiplex and omics technologies facilitating biomarker discovery are also reviewed. Finally, current and emerging therapeutic strategies targeting cytokines and growth factors, such as anti-TNF agents, IL inhibitors, anti-interferon therapies, and JAK/STAT pathway blockers, are explored. Full article

Background: Autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), Sjögren’s syndrome, systemic sclerosis (SSc), and rheumatoid arthritis (RA), pose significant challenges during pregnancy and are associated with increased risks of adverse maternal and fetal outcomes, such as preeclampsia, fetal growth restriction (FGR), miscarriage, and preterm birth. The aim of this review is to synthesize recent evidence on pregnancy-related risks, preconception counseling, and therapeutic strategies for these conditions, with a particular focus on the importance of disease remission, pregnancy-compatible medications, and the selective use of biologics. Methods: A structured narrative review was conducted through a comprehensive PubMed search (2020–2025). Eligible studies addressed maternal–fetal outcomes, therapeutic approaches, and predictive factors in pregnant individuals with autoimmune rheumatic diseases. Results: Pregnancy outcomes have improved with early disease control and multidisciplinary care; however, major challenges persist. These include limited access to novel therapies, underrepresentation of diverse populations in clinical trials, and insufficient data on long-term neonatal outcomes. The strongest predictors of adverse outcomes remain disease activity at conception, specific autoantibody profiles, and systemic organ involvement. Conclusions: Optimal pregnancy outcomes for women with autoimmune rheumatic diseases require coordinated multidisciplinary care, the use of pregnancy-compatible medications, and achievement of prolonged disease remission prior to conception. Further research is needed to close existing knowledge gaps and ensure equitable, high-quality maternal–fetal care. Full article

Objectives: Connective tissue diseases (CTDs) include a diverse group of systemic autoimmune conditions, among which interstitial lung disease (ILD) is acknowledged as a major determinant of prognosis. High-resolution computed tomography (HRCT) is the gold standard for ILD assessment. The distribution of HRCT patterns across CTDs remain incompletely defined. The objective of this systematic review is to synthesize available evidence regarding the prevalence of specific radiological patterns within CTD-ILDs and to assess whether specific patterns occur at different frequencies among individual CTDs. Methods: The inclusion criteria encompassed original human studies published in English between 2015 and 2024, involving adult participants (≥18 years) with CTD-ILDs assessed primarily by HRCT and designed as retrospective, prospective, or cross-sectional trials with extractable data. We systematically searched PubMed, Scopus, and Web of Science (January 2025). Risk of bias was evaluated using the Newcastle–Ottawa Scale (NOS) for cohort and case–control studies, and the JBI Critical Appraisal Checklist for cross-sectional studies. Data were extracted and categorized by HRCT pattern for each CTD, and then summarized descriptively and statistically. Results: We analyzed 23 studies published between 2015 and 2024, which included 2020 patients with CTD-ILDs. The analysis revealed non-specific interstitial pneumonia (NSIP) as the most prevalent pattern overall (36.5%), followed by definite usual interstitial pneumonia (UIP) (24.8%), organizing pneumonia (OP) (9.8%) and lymphoid interstitial pneumonia (LIP) (1.25%). HRCT distribution varied by CTD: NSIP predominated in systemic sclerosis, idiopathic inflammatory myopathies, and mixed connective tissue disease; UIP was most frequent in rheumatoid arthritis; LIP was more common in Sjögren’s syndrome. While global differences were statistically significant, pairwise comparisons often lacked significance, likely due to sample size constraints. Discussion: Limitations include varying risk of bias across study designs, heterogeneity in HRCT reporting, small sample sizes, and inconsistent follow-up, which may reduce precision and generalizability. In addition to the quantitative synthesis, this review offers a detailed description of each radiologic pattern mentioned above, illustrated by representative examples to support the recognition in clinical settings. Furthermore, it includes a brief overview of the major CTDs associated with ILD, summarizing their epidemiological data, risk factors for ILD and clinical presentation and diagnostic recommendations. Conclusions: NSIP emerged as the most common HRCT pattern across CTD-ILDs, with UIP predominating in RA. Although inter-disease differences were observed, statistical significance was limited, likely reflecting sample size constraints. These findings emphasize the diagnostic and prognostic relevance of HRCT pattern recognition and highlight the need for larger, standardized studies. Full article

Background and Objectives: Sjögren’s syndrome (SS) is a chronic autoimmune disease that affects the salivary glands and increases the risk of developing dental diseases (DDs). Chinese herbal medicines (CHMs) represent a promising alternative strategy for SS treatment; however, the association between CHMs and DD risk has not been confirmed. In this retrospective, cohort-based, nested case-control study, we explored whether or not combining CHMs with routine treatments for SS can reduce the chance of DDs. Materials and Methods: In the beginning, we recruited subjects aged 20–80 years with newly diagnosed SS who were free of DDs between 2001 and 2009 from a nationwide insurance database. We identified DD events that occurred after SS diagnosis until 31 December, 2013. Corresponding controls were randomly selected from the remaining enrollees using a pair-matched approach. We then exploited conditional logistic regression to explore the association between CHM use and subsequent risk of DD development. Results: Based on the recruited 586 DD cases and 586 non-DD controls, we noted that adding CHMs to routine SS treatment substantially correlated with a lower risk of developing DDs (adjusted odds ratio = 0.68; 95% confidence interval = 0.52–0.90). Notably, for those receiving CHM treatment for more than 365 days, CHM use greatly reduced DD susceptibility, by 44%. Conclusions: Embedding CHMs within routine SS care can prevent subsequent DDs incidence, implying the urgent need for interdisciplinary collaboration and careful treatment planning. Full article

Primary Sjögren’s syndrome (pSS) is a chronic, autoimmune rheumatic disease characterized by progressive lymphocytic infiltration of the exocrine glands, leading to inflammation and subsequent tissue damage. As a multifactorial disease, its etiology is complex, making it difficult to predict disease progression. Among the environmental factors implicated in pSS, the involvement of microorganisms has gained increasing attention. Since the launch of the Human Microbiome Project, growing evidence has highlighted the role of dysbiosis in the pathogenesis of various autoimmune diseases, including pSS. Shifts in the abundance of specific bacterial phyla can lead to corresponding changes in the levels of key microbial metabolites involved in tissue homeostasis and immune regulation—such as short-chain fatty acids (SCFAs), choline, taurine, serine, lactate, and tryptophan and their metabolites. Understanding the mechanisms by which these metabolites influence immune processes may provide deeper insights into the progression of the disease. Therefore, this review aims to explore the mechanisms through which microbiota-derived metabolites contribute to the pathophysiology of primary Sjögren’s syndrome. Full article

Background/Objectives: The impact of nutritional interventions on Sjögren disease (SD) remains uncertain, and no standardized guidelines currently exist for managing its sicca symptoms. This systematic review evaluated the effects of dietary interventions on the symptoms of dry mouth and dry eyes in individuals with SD. Methods: Electronic searches were performed in four databases, supplemented by manual searches and searches of the gray literature. Both human and animal studies were included. The methodological quality of the selected studies was appraised, and the data were analyzed descriptively. Results: A total of nineteen studies (ten in humans and nine in animal models) were included. The treatments evaluated were dietary supplements, vitamins, medicinal herbs, and specially modified diets. The primary outcomes assessed included unstimulated and stimulated whole salivary flow rates, salivary-gland inflammation, and ocular dryness (Schirmer test). In animal models of SD, interventions such as caloric restriction, gluten-free diets, low-fat diets, and supplements (e.g., resveratrol, triptolide, and Lycium barbarum polysaccharide) were associated with increased salivary flow and reduced glandular inflammation. Conversely, diets rich in saturated fats were associated with reduced salivary flow and increased lymphocytic infiltration in salivary glands. Human studies yielded mixed results, with some reporting improvements in salivation following interventions with vitamins, herbal supplements, gluten-free diets, liquid diets, and whole-food, plant-based diets. Conclusions: Although dietary management may alleviate sicca symptoms and improve nutritional status in SD, the current evidence is insufficient to support specific recommendations for the management of oral symptoms. Full article

Background: Autoimmune diseases and other immune-mediated disorders are associated with an increased risk of malignancy, influenced by chronic inflammation, immune dysregulation, and treatment-related factors. Clarifying cancer risk patterns across specific conditions is essential to improve clinical vigilance and inform screening practices. Objective: The aim of this study was to synthesise current evidence on the association between autoimmune and immune-mediated diseases and cancer, with a focus on practical implications for clinicians. Methods: Recent cohort studies, meta-analyses, and expert consensus documents were analysed to describe cancer epidemiology, pathogenic mechanisms, high-risk phenotypes, and treatment considerations across major autoimmune diseases and other immune-mediated conditions. The review covers idiopathic inflammatory myopathies, Sjögren’s syndrome, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, ANCA-associated vasculitis, giant cell arteritis, polymyalgia rheumatica, sarcoidosis, mixed connective tissue disease, IgG4-related disease, VEXAS syndrome, and eosinophilic fasciitis. Special attention was given to identifying warning features for underlying malignancy and evaluating cancer screening strategies. Results: The magnitude and distribution of cancer risk vary across diseases. In some conditions such as dermatomyositis, systemic sclerosis or Sjögren’s syndrome, increased risk is well established, particularly for haematological and certain solid tumours. However, tumour patterns may differ across populations, and findings are not always consistent. Distinct clinical and serological features help stratify individual cancer risk and may guide the intensity of screening. The first years after disease onset often represent a window of higher vulnerability, during which intensified surveillance may be warranted in selected patients. Conclusions: Cancer risk in autoimmune diseases should be assessed on an individual basis. Awareness of disease-specific risk factors and clinical warning signs supports early recognition of malignancy and informs screening decisions in routine practice. Full article

Chimeric antigen receptor (CAR) T cell immunotherapy has changed the landscape of B cell hematological malignancies’ management, while it has recently shown promising results in the treatment of refractory autoimmune rheumatic disorders (ARDs). Targeting B cell antigens such as CD19 and BCMA, CAR-T cell therapy can induce sustained remission by the elimination of autoreactive B cell populations resistant to the standard of care treatment options. Clinical data from case reports and small case series demonstrate profound clinical responses in ARDs, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), rheumatoid arthritis (RA), antiphospholipid syndrome (APS), and primary Sjögren’s syndrome (pSS). Treatment outcomes include reduced disease activity, normalization of serologic markers, improved organ function, and drug-free remission, even after B cell reconstitution. Additionally, toxicities, primarily limited to mild cytokine release syndrome (CRS), were generally manageable with supportive care. Encouraging preliminary results have led to the development of several ongoing clinical trials investigating CAR-T cell therapy across multiple ARDs and patient populations, including pediatric patients. This review summarizes the current clinical experience and provides a comprehensive overview of ongoing clinical trials exploring CAR-T cell immunotherapy for ARDs. Full article