Search Results (108)

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

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

The EORTC/MSGERC definition lacks sufficient sensitivity for diagnosing invasive pulmonary aspergillosis (IPA) in patients with autoimmune inflammatory rheumatic diseases (AIIRDs). We hypothesized that the partial fulfillment of the EORTC/MSGERC definition can improve its diagnostic sensitivity. This retrospective observational study included patients with AIIRDs on immunosuppressive therapy who underwent serum galactomannan antigen testing for suspected IPA. Patients who fulfilled the clinical features or mycological evidence as per the EORTC/MSGERC definition were considered as having “potential IPA.” We compared the clinical characteristics of 364 patients who were categorized into 3 groups—potential IPA (n = 29), proven/probable IPA (n = 24), and non-IPA (n = 311; not meeting any definition). The potential and proven/probable IPA groups had significantly lower survival rates than the non-IPA group (p < 0.001). The potential IPA (adjusted hazard ratio [aHR], 2.0; 95% confidence interval [CI], 1.1–3.8) and proven/probable IPA (aHR, 2.6; 95% CI, 1.4–4.9) were independent risk factors for mortality. Compared with the EORTC/MSGERC definition, our proposed criteria improved sensitivity based on the diagnosis at the end of observation (50.0%, 100.0%, respectively). The characteristics and mortality rates of patients were similar between the potential and proven/probable IPA groups. Using these criteria for clinical diagnosis may provide high sensitivity. Full article

Background and Objectives: Psoriatic arthritis (PsA) is a chronic rheumatic disease that is frequently associated with fibromyalgia (FM). The coexistence of FM complicates the evaluation of PsA disease activity and the planning of treatment strategies, as the two conditions share many overlapping clinical symptoms. To investigate the contribution of demographic factors and available serum biomarkers of inflammation and autoimmunity in characterizing the heterogeneity among patients meeting the classification criteria for both PsA and FM. Materials and Methods: This cross-sectional, single-center study involved 1547 adult patients evaluated between January 2017 and December 2024 who met the CASPAR criteria for PsA. A patient subgroup also met the 2016 ACR criteria for FM. Demographic data, serum inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and autoimmunity markers including antinuclear antibodies (ANA), rheumatoid factor (RF), and anti-citrullinated protein antibodies (ACPA) were evaluated. Statistical analyses included chi-square tests, t-tests, Mann–Whitney U tests, and multivariate logistic regression to identify independent predictors associated with the coexistence of PsA and FM. Results: A total of 254 patients (16.42%) were diagnosed with concomitant FM. Compared to patients with PsA alone, those with concurrent PsA and FM showed significantly lower C-reactive protein (CRP) levels (0.39 ± 0.74 vs. 2.88 ± 12.31 mg/dL; p < 0.001) and a higher frequency of antinuclear antibody (ANA) positivity (13.57% vs. 5.78%; p < 0.001). No significant differences were observed in rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA) positivity between the groups. Multivariate logistic regression identified female sex, ANA positivity, CRP levels ≤ 0.5 mg/dL, and elevated body mass index (BMI) as independent predictors of the presence of concomitant FM. Conclusions: Patients with concomitant PsA and FM have a distinct demographic and serological profile, suggesting the existence of a clinically significant subgroup within the PsA population. Recognition of these differences may improve diagnostic accuracy and support the development of personalized, non-immunosuppressive therapeutic strategies for this subgroup of patients. 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

Rheumatoid arthritis (RA) is the most common chronic autoimmune arthropathy. If the disease is aggressive or left untreated, it becomes debilitating, affects a patient’s functionality, and reduces the quality of life. Disease-modifying anti-rheumatic drugs (DMARDs), both conventional, targeted, and biological, decrease the disease progression and are key components of effective treatment. Recently, there has been a continuous debate about the possible carcinogenicity of various DMARDs. Lung cancer is a leading cause of cancer death worldwide. The available data show an increased risk of lung cancer in RA patients, but the link between RA and cancer is poorly understood. Carcinogenesis in RA seems to be related to chronic inflammation, familial predisposition, risky behaviors (e.g., smoking), and iatrogenic complications. The main mechanisms of carcinogenic processes in patients with RA are the up-regulation of interleukin-6 (IL-6) cytokine production and wingless/integrated WNT signaling. Up-regulation of WNT5A is an important mechanism that links chronic inflammatory pathways to carcinogenesis observed in RA patients. Concomitant up-regulation of transcription factor STAT3 promotes cell proliferation and inhibits apoptosis. Conversely, suppressed inflammatory processes by DMARDs may decrease the risk of lung cancer. In this article, we discuss the molecular mechanisms of lung cancer in RA and the role of DMARDs in this process. Furthermore, we analyze the molecular effect of drug-induced cancer, which affects transcription factors and thus modulates carcinogenic processes. Finally, we describe risk factors and present preventive and therapeutic approaches. 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

Cardio-rheumatology is an evolving and interdisciplinary field lying at the intersection of rheumatology and cardiovascular medicine that recognizes that individuals with autoimmune and inflammatory rheumatic complications have a much higher likelihood of developing cardiovascular diseases (CVDs). Inflammasomes are multiprotein complexes stimulated by the immune system after the detection of pathogens or cellular injury. Inflammasomes undergo a two-stage activation process initiated by nuclear factor (NF)-κB, subsequently playing a crucial role in innate immunity through activation of caspase 1 and the consequent release of proinflammatory cytokines such as IL-18 and IL-1β. However, a loss of control of inflammasome activation can cause inflammatory diseases in humans. Recent studies have focused on the role of inflammasomes in inflammatory cascades implicated in the pathogenesis of several diseases. Here, we review inflammasome activation, its mechanism of action, and its role in CVD. In particular, we describe the role of inflammasomes in rheumatic heart disease, Kawasaki disease, familial Mediterranean fever, ankylosing spondylitis, and rheumatoid arthritis as exemplars to illustrate pathobiological mechanisms and the potential for targeting inflammasomes for therapeutic benefit. Full article

Rheumatoid arthritis (RA) is a chronic, common autoimmune disease. It is characterized by inflammatory polyarthritis, which can lead to permanent disability in patients. Current treatment is mainly symptom-related, aiming to reduce pain and inflammation, but does not lead to a full recovery. This treatment includes non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs). It has been shown that, due to chronic inflammation, reduced glucose levels and hypoxia, endoplasmic reticulum (ER) stress is induced in RA patients, leading to the activation of multiple signaling pathways, including the ER-dependent adaptation of the unfolded protein response (UPR) pathway. The aim of this study was to assess the level of apoptosis in patients diagnosed with RA. The study sought to investigate whether UPR response correlated with apoptosis induction could serve as a potential diagnostic marker or therapeutic target. In vitro studies have shown that UPR pathway activity can be observed in patients diagnosed with RA. The study group consisted of PBMC cells from 61 individuals, including a total of 31 rheumatoid arthritis patients and 30 healthy controls. In order to validate UPR activation, we estimated molecular markers of ER stress via RT-qPCR expression analysis. GAPDH expression was used as a standard control. Elevated levels of mRNA for the eIF2α (p-value = 0.001903), the BBC3 (PUMA) (p-value = 0.007457 × 10⁻⁷) and the TP53 (p-value = 0.002212) were confirmed in a group of RA patients. Further analysis showed that after the induction of apoptosis the percentage of DNA contained in the tail was 37.78% higher in RA patients than in the control group (p-value = 0.0003) measured by comet assay. The exogenous damage caused by hydrogen peroxide was found to be statistically elevated in RA patients and the caspase-3 level was calculated of 40.17% higher than in controls (p-value = 0.0028). It was also found that PBMC cells from RA patients were more sensitive to apoptotic induction. Our results were confirmed by flow cytometry. The most important finding from our data was the confirmation of elevated sensitivity to apoptosis induction in RA patients; the results showed a 40.23% higher percentage of cells in early apoptosis than in the control group (p-value = 0.0105). Our results may help to assess the feasibility of the application of early diagnosis and targeted therapy in the treatment of RA patients, including the ER signaling pathway via selected UPR-dependent molecular inhibitors. Full article

Rheumatic diseases encompass a wide range of autoimmune and inflammatory disorders, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), and systemic sclerosis (SSc). These conditions often result in chronic pain, disability, and reduced quality of life, with unpredictable disease courses that may lead to joint destruction, organ damage, or systemic complications. Biomarkers, defined as measurable indicators of biological processes or conditions, have the potential to transform clinical practice by improving disease diagnosis, monitoring, prognosis, and treatment decisions. While significant strides have been made in identifying and validating biomarkers in rheumatic diseases, challenges remain in their standardization, clinical utility, and integration into routine practice. This review provides an overview of the current state of biomarkers in rheumatic diseases, their roles in clinical settings, and the emerging advancements in the field. Full article

Rheumatoid arthritis (RA) is a long-term systemic autoimmune disorder that causes joint inflammation, swelling, pain, bone erosion, and deformities. Recent findings emphasize the anti-inflammatory and antioxidant properties of bioactive natural compounds, such as polyphenols extracted from plants and fruits, and their possible synergistic effect when used in combination with current therapies to improve the prognosis and symptoms of inflammatory rheumatic diseases. Here, we report that Sicilian extra virgin olive oil polyphenol-enriched extracts (PE-EVOOs) reduce intracellular reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), in peripheral mononuclear cells (PBMCs) obtained from both RA patients and healthy subjects (HSs) treated with lipopolysaccharides (LPS) as a control. HPLC-ESI-MS analysis highlighted that PE-EVOOs are rich in different polyphenolic compounds responsible for many of the observed biological effects. At molecular levels, Western blotting analyses revealed that PE-EVOO treatment is associated with the downregulation of the phosphorylated and active form of the inflammatory transcription factor NF-κB and the pro-inflammatory enzyme cyclooxygenase 2 (COX2). In addition, PE-EVOOs upregulated the transcription factor Nrf2 and its target antioxidant enzyme catalase and manganese superoxide dismutase (MnSOD). Collectively, these results suggest a possible use of PE-EVOOs as potential adjuvants for the treatment of RA. Full article

Rheumatoid arthritis (RA), an autoimmune disease with complex pathogenesis, is characterized by an immune imbalance reflected, e.g., in the disturbed cytokines’ profile. Various viruses and bacteria can cause the upregulation of pro-inflammatory cytokines influencing RA development. In particular, oral cavity dysbiosis, observed in multiple chronic diseases including periodontitis, may be linked to RA. The cytokine profile (IL-1β, IP-10, IL-29, GM-CSF, IFN-α2, IFN-β, TGF-β1, MPC-1, TNF-α, IFN-γ, IL-6, IL-10, IL-17A, IL-12p70, IL-2, and IL-4) of RA patients’ saliva was evaluated using flow cytometry and benchmarked with their levels in saliva of healthy controls and patients with other rheumatic diseases. The levels of IL-1β, IP-10, IL-2, and IL-4 were significantly elevated in RA patients’ saliva compared to other studied groups. To define the potential role of the most suspicious microbial agents (Epstein–Barr Virus (EBV), Cytomegalovirus, Parvovirus B19, Porphyromonas gingivalis, and Segatella copri) for RA pathogenesis, the amounts of their DNA in the saliva of patients with RA were assessed in all the groups mentioned above. The EBV and P. gingivalis DNA levels measured by qRT-PCR were significantly higher in RA patients’ saliva than in other groups, indicating either the important role of these agents in RA pathogenesis or the higher susceptibility of RA patients for those infectious factors. The comprehension of the association of specific cytokine profiles in RA and the occurrence of specific viral and/or bacterial infections can be a key to a better understanding of RA pathogenesis. These results illustrate the complexity of the immunological profile of RA, show the high diagnostic potential of saliva, and provide insight into how various infections can contribute to RA development. Full article

Interstitial lung disease (ILD) is one of the common and potentially lethal manifestations of systemic autoimmune rheumatic diseases (SARDs). ILD’s prevalence, clinical patterns, imaging, and natural history are variable. Each of the representative diseases—systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), rheumatoid arthritis (RA), Sjӧgren’s syndrome (SjS), mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE)—have distinct clinical, paraclinical and evolutionary features. Risk factors with predictive value for ILD have been identified. This review summarizes, from the clinician’s perspective, recent data from the literature regarding the specificity of ILD for each of the autoimmune rheumatic diseases, with an emphasis on the role of the multidisciplinary team in early diagnosis, case management, as well as the particularities of the clinical approach to the progressive phenotype of ILD in SARDs. Full article

Background: This communication summarizes our single-center experience with the use of anti-IL-1 biologic response modifiers for treating autoimmune and autoinflammatory conditions in children. Methods: We outline our rationale for the off-label use of anakinra and discuss emerging treatment paradigms that necessitate further research and validation. Results: Anakinra has enabled personalized treatment, whether used as a single agent on an as-needed basis, as part of a background treatment regimen, or in combination with colchicine. Our data also highlight the significance of anakinra in treating post-infectious inflammatory diseases, demonstrating its high efficacy in novel applications such as rheumatic fever and post-viral arthritis. Canakinumab, on the other hand, has provided long-term remission. Both medications were well-tolerated, with no serious adverse effects reported. Conclusions: Based on our observations and successful outcomes, we advocate for future collaborative efforts to improve access to anti-IL-1 medications to better manage excessive and harmful inflammation in children. Full article