Search Results (132)

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

The precipitation of cryoglobulins, serum immunoglobulins, below 37 °C defines the clinical cryoglobulinemic syndrome, a systemic vasculitis usually characterized by purpura, weakness, and arthralgia. In most cases, this condition is associated with chronic infection by the hepatitis C virus (HCV) and can evolve into B-cell dysregulation and malignancies. The current literature on non-HCV-associated cryoglobulinemia is very limited, and little is known about the immunological and serological profile of affected patients. The cryoglobulinemic syndrome not associated with HCV infection is often found concomitantly with other infections, autoimmune diseases, and B-cell lymphoproliferative disorders. The cryoprecipitation of fibrinogen has been described as a rare disorder, perhaps underestimated and not fully understood, causing thrombotic occlusion and ischemia in different rheumatic disorders. Cold temperature plays a pathogenetic role in autoimmune hemolytic anemias, in which the presence of cold agglutinins produced by B cells at the lymphoplasmacytic cell stage may promote agglutination of red blood cells in the coldest parts of the circulation, even at mild room temperatures, undergoing hemolysis. Laboratory methods for the detection and quantification of cryoproteins are downright critical, and their concurrent detection is pivotal for the diagnosis. In this review, we summarize the clinical involvement of cryoglobulins, cryofibrinogen, and cold agglutinins in non-HCV autoimmune diseases, underlining the crucial steps of the most employed analytic methods. Full article

Background: Women with systemic autoimmune rheumatic disease (SARD) are at higher risk of developing infection-related complications, anxiety, and depression. Using the example of the COVID-19 pandemic, we aimed to explore the impact of this external stressor on symptoms of depression, anxiety, and stress in a sample of women with SARD in a cross-sectional study design. Methods: Females aged 18–50 with SARD were enrolled from 04/2021 to 04/2022 at the Medical University of Vienna or through an online self-help group, while snowball sampling was used to recruit an age-matched healthy control group. Participants completed questionnaires including: (1) demographic information, medical history, and access to healthcare; (2) the Depression, Anxiety, and Stress Scale (DASS-21); and (3) the Coronavirus Anxiety Scale (CAS). Parameters were compared between groups using Chi-squared, Fisher’s exact, and Mann–Whitney U tests. Linear regression analysis was used to investigate which individual factors predicted the DASS-21 in women with SARD. Results: The study sample consisted of 226 women (n = 99 with SARD and n = 127 healthy controls). Women with SARD reported lower DASS-21 stress (p = 0.008) and CAS scores (p = 0.057) than the control group. There were no significant differences in DASS-21 anxiety or depression scores. Among women with SARD, a linear regression model identified the most important predictors of DASS-21 as access to rheumatological care (p = 0.002) and recent disease activity (p = 0.028). Conclusions: Despite the pandemic, women with SARD reported mental health outcomes equal to or better than those of the healthy control group. Continued access to rheumatological care may serve as an important protective factor for their mental health during large-scale crises like pandemics. Full article

Rheumatoid arthritis (RA) is a progressive and systemic autoimmune disease, characterized by a chronic inflammatory process, affecting the lining of the synovial joints, many body organs/systems, and blood vessels. Its pathological hallmarks are hyperplasic synovium, bone erosion, and progressive joint destruction. Rheumatoid arthritis affects over 20 million people, with a worldwide prevalence of 0.5–1.0%, exhibiting gender, ethnic, and geographical differences. The progressive disability severely impairs physical motion and quality of life and is finally leading to a shortened life span. The pathogenesis of RA is a complex and still poorly understood process in which genetic and environmental factors are principally associated. Current treatment mostly relies on conventional/non-biological disease-modifying anti-rheumatic drugs (cDMARDs), analgesics, non-steroidal anti-inflammatory drugs, glucocorticoids, steroids, immunosuppresants, and biologic DMARDs, which only control inflammation and pain. Along with side effects (drug toxicity and intolerance), these anti-rheumatic drugs possess limited efficacy. Therefore, the discovery of novel multi-target therapeutics with an improved safety profile that function as inhibitors of RA-linked signaling systems are in high demand, and this is in the interest of both patients and clinicians. Plant-derived extracts, nutritional supplements, dietary medicine, and molecules with anti-inflammatory activity represent promising adjuvant agents or alternatives for RA therapeutics. This review not only aims to discuss the basic features of RA pathogenesis, risk factors, and signaling pathways but also highlights the research progress in pre-clinical RA in in vitro and in vivo models, revealing new avenues in the management of the disease in terms of comprehensive multidisciplinary strategies originating from medicinal plants and plant-derived molecules. Full article

Sjögren’s Disease (SjD), Rheumatoid Arthritis (RA), and Systemic Lupus Erythematosus (SLE) are autoimmune diseases with overlapping genetic features, yet the etiologies of these diseases are poorly understood. Using these rheumatic diseases as an example of proof of concept, our aim was to develop a tool that simplifies analysis of gene–disease associations applicable to any disease and to perform comparisons. This tool is meant to provide insights into associated gene symbols and gene expression data to identify candidate biomarkers in common among these diseases. The Diseasesv2.0 and GTExv8 databases were utilized for data collection, providing searchable disease names, affiliated gene symbols, confidence scores (ranging from 0 to 5, with 5 being the most confident), and gene expression across the panel of 54 tissue types present in GTExv8. Data infrastructure was established on a Postgres database using Plotlyv5.17.0 and Streamlitv1.27.2 Python packages. The resulting database was used to investigate the genetic associations among SjD, RA, and SLE, including confidence scores from 2.50 to 5.00. STRINGv12 analysis determined significant pathways (FDR < 0.05). Analysis using our tool revealed the following refined gene associations for each disease: SjD based on ‘Sjogren’ search term (n = 12 genes), RA (n = 231 genes), and SLE (n = 137 genes). We found seven genes in common, namely, CD4, CD8A, IL6, IL17A, TNFS13B, TNF, and TRIM21. With the exception of IL17A, these genes were expressed in tissue types known or suggested to be affected by SjD. STRINGv12 determined significant KEGG pathways involving interleukin signaling, cytokine signaling, and the immune system. We developed a tool that simplifies the data mining process, allowing users to search for diseases of interest and view common gene associations and gene expression. Some of the genes identified through our tool may be further explored to better understand SjD pathogenesis and systemic impact. Full article

Connective tissue diseases (CTDs) comprise a heterogeneous group of autoimmune conditions characterized by diverse clinical manifestations and autoantibody profiles, posing significant diagnostic challenges. This systematic review and meta-analysis evaluated the diagnostic performance of automated connective tissue disease screening assays, commonly known as CTD screens, in diagnosing systemic rheumatic diseases. Eleven studies, including cohort and case–control designs, involving a total of 2384 CTD-positive patients, 8972 controls without CTD, and 679 healthy blood donors, were analyzed. The results demonstrated a pooled sensitivity of 79.36% and specificity of 90.79% for Elia^® CTD-screen, and a sensitivity of 87.23% and specificity of 83.56% for QuantaFlash^® CTD-screen. These tests exhibited varied sensitivity across individual CTDs, with excellent specificity for distinguishing CTD patients from healthy controls. Despite their utility, CTD screens should not be solely relied upon for diagnosis due to limitations in positive predictive value, particularly in low-prevalence populations. Clinical context and expert rheumatological evaluation remain indispensable. Optimizing the use of CTD screens can enhance diagnostic efficiency, reduce unnecessary testing, and mitigate patient anxiety and healthcare costs. Further research focusing on integrating these assays with clinical evaluation is recommended. Full article

Background/Objectives: Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) exhibit increased cardiovascular risk, partly attributed to persistent systemic inflammation. Janus kinase inhibitors (JAKi) effectively reduce inflammation, but their impact on cardiovascular risk remains unclear. This pilot study aimed to evaluate the effect of JAKi therapy on systemic inflammation and lipid markers, correlate traditional cardiovascular risk factors with biological parameters, and quantify subclinical atherosclerosis progression. Methods: We conducted a prospective, single-center study including 48 patients receiving JAKi. Clinical, inflammatory, lipid, and vascular parameters were assessed at baseline (T0) and after 12 months (T1). Primary endpoints included changes in carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and carotid plaque presence. Results: Mean cIMT significantly decreased from 0.29 mm to 0.125 mm (p = 0.019), while ABI improved modestly, but not significantly (0.125 to 0.04, p = 0.103). Carotid plaque prevalence increased slightly from 39.6% to 47.9%, p = 0.159. C-reactive protein (CRP) levels declined significantly, while interleukin (IL)-1β levels increased. Lipoprotein(a) [Lp(a)] levels decreased significantly (mean reduction −7.96 mmol/L, p = 0.001). Multivariate regression identified Lp(a) as an independent predictor of carotid plaque at both T0 (p = 0.011) and T1 (p = 0.005). Baseline ABI was a significant predictor of acute cardiovascular events [hazard ratio (HR): 4.614, 95% CI: 1.034–20.596, p = 0.045]. Conclusions: JAKi therapy significantly reduced systemic inflammation and cIMT in patients with autoimmune rheumatic diseases, suggesting a potential benefit in attenuating early vascular changes. However, residual cardiovascular risk remains in patients with low ABI and elevated Lp(a), warranting close monitoring. Full article

Systemic autoimmune rheumatic diseases (SARDs), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s syndrome (SS), are traditionally characterized by chronic inflammation and immune-mediated damage to joints and other tissues. However, many patients also experience symptoms such as widespread pain, persistent fatigue, cognitive dysfunction, and autonomic disturbances that cannot be attributed directly or entirely to peripheral inflammation or structural pathology. These conditions suggest the involvement of interactions between the nervous and immune systems, which probably include both peripheral and central components. This review summarizes the current knowledge of neurological and neuroimmune mechanisms that may contribute to these symptoms in SARDs. Glial cell activation and neuroinflammation within the central nervous system (CNS), small-fiber neuropathy (SFN) affecting peripheral nociceptive pathways, central pain sensitization, and autonomic nervous system dysfunction will be discussed. In addition, the role of molecular mediators, including cytokines, neuropeptides, and microRNAs, that could potentially modulate neuroimmune signaling will be highlighted. Integrating findings from pathology, immunology, and neuroscience, this review seeks to provide a useful framework for understanding neuroimmune dysregulation in SARDs. It also highlights the clinical relevance of these mechanisms and summarizes new directions for diagnosis and treatment. Full article

Background/Objectives: Autoimmune inner ear disease (AIED) causes sensorineural hearing loss that classically presents as fluctuating, asymmetric loss of hearing. Associated vestibular and other ear symptoms can be present in many patients. First-line treatment of AIED is high-dose corticosteroids. AIED can present either as a primary condition limited to ear involvement or secondary, as part of an underlying systemic autoimmune rheumatic disease, the most common of which include vasculitis and relapsing polychondritis. We described our cohort of primary AIED, including demographics, treatment, and outcomes. We excluded from this review sensorineural hearing loss in the context of vasculitis and relapsing polychondritis. Methods: We performed a chart review of patients with the diagnosis of AIED at Mayo Clinic and compared the cohort by sex. Results: Thirty-one patients met the inclusion criteria. The mean age was 48.5 years, and 17 were men. Patients were initially evaluated at the Department of Otorhinolaryngology or Internal Medicine, and 29 patients were subsequently referred to the Department of Rheumatology, with a mean of 12.2 weeks after the first evaluation. Treatment with corticosteroids showed improvement in hearing and vestibular symptoms during the first month but no further improvement by the end of the third month. Other immunosuppressive medications were used with various degrees of response. Methotrexate was the second most used therapy, with 11 of 17 patients reporting an improvement in symptoms. Conclusions: Corticosteroid therapy is an effective initial treatment for AIED and should be followed with corticosteroid-sparing agents to prevent further damage to the cochlea. Full article

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease that affects various organs, including the kidneys. Despite recent advancements, effective treatment options for renal involvement in SLE remain limited. Rebamipide, originally developed as a gastroprotective agent, has been reported to exert immunomodulatory effects in rheumatic diseases. Here, we aimed to evaluate the therapeutic potential of rebamipide in SLE using an animal model and to elucidate its mechanisms of action. We administered rebamipide or vehicle control to lupus-prone MRL/lpr mice and evaluated its efficacy on lupus-like phenotypes, including renal manifestations and immune cell profiles. Additionally, we investigated potential therapeutic mechanisms through in vitro treatment of murine immune cells and podocytes with rebamipide. Oral administration of rebamipide in lupus-prone mice significantly reduced kidney size, weight, and histopathological inflammation. Among circulating immune cell subsets, only regulatory T cells were significantly increased by rebamipide. In vivo treatment with rebamipide enhanced the expression of podocyte structural proteins, such as Synaptopodin, in kidney tissues, accompanied by the recovery of antioxidative factors, including nuclear factor erythroid 2-related factor 2 (Nrf2). Similarly, in vitro treatment of murine immune cells and podocytes with rebamipide replicated its immunoregulatory and antioxidative effects. Rebamipide is proposed as a potential therapeutic candidate for managing renal involvement in SLE through its antioxidative effects on podocytes. Full article

Objective: 3-Nitrotyrosine (3-NT) is a byproduct of tyrosine nitration, mediated by reactive nitrogen species such as peroxynitrite and nitrogen dioxide. It serves as a marker of cellular damage, inflammation, and nitric oxide activity. Rheumatoid arthritis (RA) is a complex autoimmune disease characterized by systemic involvement and increased oxidative stress. In RA patients, cardiovascular disease has emerged as the leading cause of mortality. This study aimed to investigate the relationship between serum 3-NT levels and various disease characteristics in RA patients, with a particular focus on cardiovascular comorbidities. Methods: A total of 168 RA patients were recruited. They underwent comprehensive evaluations, including disease-related characteristics and disease activity indices. Furthermore, a comprehensive lipid panel, measures of insulin resistance, metabolic syndrome criteria, and carotid ultrasound to evaluate intima–media thickness and the presence of carotid plaques were conducted. 3-NT serum levels were measured. A multivariable linear regression analysis was performed to examine the associations between the disease characteristics and 3-NT. Results: After multivariable analysis, C-reactive protein was independently associated with higher serum levels of 3-NT. In contrast, disease characteristics and Disease Activity Score 28-joint count (DAS28) calculated using C-reactive protein or erythrocyte sedimentation rate, showed no significant association with 3-NT levels. Likewise, cardiovascular comorbidities, including lipid profiles, insulin resistance indices, metabolic syndrome, and markers of subclinical atherosclerosis did not demonstrate any significant relationship with 3-NT levels. Conclusions: While 3-NT levels are influenced by inflammation, they do not appear to be strongly associated with disease characteristics, cardiovascular risk, or disease-modifying anti-rheumatic drugs in RA patients. This emphasizes the complexity of oxidative stress in RA. Full article

Rheumatic diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are chronic autoimmune disorders characterized by persistent inflammation and oxidative stress, leading to joint damage and reduced quality of life. In recent years, increasing attention has been given to diet as a modifiable environmental factor that can complement pharmacological therapy. This review summarizes current evidence on how key dietary components—such as omega-3 fatty acids, fiber, polyphenols, and antioxidant vitamins—affect inflammatory pathways and oxidative balance. Special emphasis is placed on the Mediterranean diet, low-starch diets, and hypocaloric regimens, which have shown potential in improving disease activity. The gut microbiota emerges as a critical mediator between diet and immune function, with dietary interventions capable of restoring eubiosis and strengthening the intestinal barrier. Additionally, this paper discusses challenges in the clinical implementation of diet therapy, the need for personalized nutritional strategies, and the importance of integrating diet into holistic patient care. Collectively, findings suggest that dietary interventions may reduce disease activity, mitigate systemic inflammation, and enhance patients’ overall well-being. Full article

Inflammation is a multifaceted biological response of the immune system against various harmful stimuli, including pathogens (such as bacteria and viruses), cellular damage, toxins, and natural/synthetic irritants. This protective mechanism is essential for eliminating the cause of injury, removing damaged cells, and initiating the repair process. While inflammation is a fundamental component of the body’s defense and healing process, its dysregulation can lead to pathological consequences, contributing to various acute and chronic diseases, such as autoimmune disorders, cancer, metabolic syndromes, cardiovascular diseases, neurodegenerative conditions, and other systemic complications. Generally, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying anti-rheumatic drugs (DMARDs), antihistamines, biologics, and colchicine are used as pharmacological agents in the management of inflammatory diseases. However, these conventional treatments often have limitations, including adverse side effects, long-term toxicity, and drug resistance. In contrast, enzyme-based therapeutics have emerged as a promising alternative due to their high specificity, catalytic efficiency, and ability to modulate inflammatory pathways with reduced side effects. These enzymes function by scavenging reactive oxygen species (ROS), inhibiting cytokine transcription, degrading circulating cytokines, and blocking cytokine release by targeting exocytosis-related receptors. Additionally, their role in tissue repair and regeneration further enhances their therapeutic potential. Most natural anti-inflammatory enzymes belong to the oxidoreductase class, including catalase and superoxide dismutase, as well as hydrolases such as trypsin, chymotrypsin, nattokinase, bromelain, papain, serratiopeptidase, collagenase, hyaluronidase, and lysozyme. Engineered enzymes, such as Tobacco Etch Virus (TEV) protease and botulinum neurotoxin type A (BoNT/A), have also demonstrated significant potential in targeted anti-inflammatory therapies. Recent advancements in enzyme engineering, nanotechnology-based enzyme delivery, and biopharmaceutical formulations have further expanded their applicability in treating inflammatory diseases. This review provides a comprehensive overview of both natural and engineered enzymes, along with their formulations, used as anti-inflammatory therapeutics. It highlights improvements in stability, efficacy, and specificity, as well as minimized immunogenicity, while discussing their mechanisms of action and clinical applications and potential future developments in enzyme-based biomedical therapeutics. Full article

In recent years, autoimmune diseases are becoming more and more prevalent worldwide, with this rapid rise being influenced by environmental factors linked to lifestyle changes in modern societies. In this context, the role of diet has been the topic of extensive research as evidence has mounted that particular dietary patterns may contribute to or modulate autoimmunity. The present review specifically focuses on the Mediterranean diet (MD) as a whole dietary pattern, and on its peculiar components, such as n-3 polyunsaturated fatty acids (PUFAs), polyphenols and fiber. We explored their potential benefits in a spectrum of both systemic and organ-specific autoimmune disorders, including rheumatic diseases (like rheumatic arthritis and systemic lupus erythematosus), and thyroid diseases (like Hashimoto’s thyroiditis), since they often occur in the same individuals. Here, we offer a comprehensive review about the influence of dietary factors on these autoimmune diseases and potential translation into therapeutic interventions, as an adjuvant therapeutic approach to improve autoimmunity-related outcomes. Full article

Vitamin D is a fat-soluble molecule with pleiotropic effects, acting as a steroid hormone on three main organs: the intestine, bone, and kidney. Among its best-known functions at the skeletal level are regulating bone metabolism and mineralization. In 1983, the presence of vitamin D receptors on the surface of immune cells was described, which led to the discovery of new functions on immunological and inflammatory processes. Currently, we know that vitamin D modulates the adaptative immune system by suppressing cells that produce inflammatory cytokines by downregulation, acting as an important regulator of immunity and the inflammatory response. In this article, we will review the synthesis, metabolic pathways, and the role of vitamin D in rheumatic autoimmune diseases. Full article