Search Results (164)

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. Aim: to investigate autoantibodies, cytokines, and genetic markers in SSc-ILD through a systematic review and analysis of a Kazakh cohort of SSc-ILD patients. Methods: A PubMed search over the past 10 years was performed with “SSc-ILD”, “autoantibodies”, “cytokines”, and “genes”. Thirty patients with SSc were assessed for lung involvement, EScSG score, and modified Rodnan skin score. IL-6 was measured by ELISA, antinuclear factor on HEp-2 cells by indirect immunofluorescence, and specific autoantibodies by immunoblotting. Genetic analysis was performed using a 120-gene AmpliSeq panel on the Ion Proton platform. Results: The literature review identified 361 articles, 26 addressed autoantibodies, 20 genetic variants, and 12 cytokine profiles. Elevated levels of IL-6, TGF-β, IL-33, and TNF-α were linked to SSc. Based on the results of the systemic review, we created a preliminary immunogenic panel for SSc-ILD with following analysis in Kazakh patients with SSc (n = 30). Fourteen of them (46.7%) demonstrated signs of ILD and/or lung hypertension, with frequent detection of antibodies such as Scl-70, U1-snRNP, SS-A, and genetic variants in SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, and CD40 genes. Conclusions: Current research confirmed the presence of the broad range of autoantibodies and variations in IRAK1, TNFAIP3, SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, CD40 genes in of Kazakhstani cohort of SSc-ILD patients. Full article

Background: Antinuclear antibodies (ANAs) serve as crucial biomarkers for diagnosing systemic autoimmune diseases; however, their interpretation can be complex and may not always correlate with clinical symptoms. Methods: A comprehensive narrative review was conducted to evaluate the peer-reviewed literature published between 1961 and 2025. Databases, including PubMed and Scopus, were searched using combinations of controlled vocabulary and free-text terms relating to antinuclear antibodies and their clinical significance. The objective was to gather and synthesize information regarding the diagnostic utility and interpretation of ANA testing in routine medical practice. Discussion: The indirect immunofluorescence assay (IIF) on HEp-2 cells is established as the gold standard for detecting ANAs, facilitating the classification of various fluorescent patterns. While a positive ANA test can suggest autoimmune disorders, the presence and titre must be interpreted alongside clinical findings, as low titres often lack diagnostic significance. Findings indicate that titres higher than 1:160 may provide greater specificity in differentiating true positives from false positives in healthy individuals. The study also emphasizes the relevance of fluorescence patterns, with specific patterns linked to particular diseases, although many do not have strong clinical correlations. Moreover, certain autoantibodies demonstrate high specificity for diseases like systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Ultimately, while ANA testing is invaluable for diagnosing connective tissue diseases, healthcare providers must consider its limitations to avoid misdiagnosis and unnecessary treatment. Conclusions: ANA testing is a valuable tool in the diagnosis of connective tissue diseases, but its interpretation must be approached with caution. Clinical context remains crucial when evaluating ANA results to avoid misdiagnosis and overtreatment. This review is about the diagnostic aspects and clinical consequences of ANA testing, as well as highlighting both the diagnostic benefits and the potential limitations of this procedure in everyday clinical practice. The review fills a gap in the literature by integrating the diagnostic and clinical aspects of ANA testing, with a focus on real-world interpretation challenges. Full article

Previous studies have shown that patients with a history of endometriosis have an increased susceptibility for developing a big number of comorbidities, including various autoimmune diseases. Endometriosis is a complex, inflammatory, estrogen-dependent, heterogeneous gynecological disorder with an incidence of up to 10% in women of reproductive age. It is characterized by the implantation and growth of endometrial tissue outside the uterus and is associated with dysmenorrhea, deep dyspareunia, pelvic pain and infertility. Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disorder of the connective tissue, characterized by impaired innate and adaptive immune responses and the production of pathogenic autoantibodies that drive inflammation and damage in multiple organs. Its etiology is elusive yet associated with high heritability. Importantly, it has been found that endometriosis and SLE share some underlying molecular and cellular pathways. In the present study, we sought to delineate the co-occurrence of endometriosis with SLE from the biological and genetic viewpoint, aiming to identify the putative shared genetic components and clarify the underlying pathogenetic mechanisms. This information may contribute further to the design of new therapeutic protocols for both disorders under study. Full article

Background and Clinical Significance: Neuromyelitis optica (NMO) is a chronic demyelinating inflammatory disease of the central nervous system (CNS), mediated by autoantibodies against aquaporin-4 (AQ4) receptors. In the spectrum of NMO, other autoimmune diseases also coexist, though their association with systemic lupus erythematosus (SLE) is rare. Case Presentation: We present two cases of patients in their 70s who were diagnosed with NMO in the context of SLE. The first case concerns a 78-year-old woman with drug-induced SLE and thoracic myelitis who developed T4-level incomplete paraplegia over three weeks. The second case involves a 71-year-old woman with a history of SLE and myasthenia gravis, presenting with cervical myelitis with progressive worsening of walking and C4-level paraparesis over two months. In both cases, elevated serum anti-AQ4 titers were detected, establishing the diagnosis of NMO and differentiation from an atypical manifestation of SLE-related myelitis. High doses of intravenous corticosteroids with gradual tapering, along with cyclophosphamide, followed by rituximab, were administered in both patients. The first patient showed a poor response, while the second showed improvement. Conclusions: The coexistence of NMO with SLE is rare, but the occurrence of myelitis in patients with connective tissue diseases should raise the suspicion of NMO, especially in elderly women and several years after the diagnosis of SLE. Time to treatment is critical, as delays in treating NMO can result in cumulative and disabling damage. 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

Objectives: Patients with interstitial lung disease (ILD) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at high risk of severe coronavirus disease 2019. It is unclear whether anti-viral cellular and humoral immunity is impacted in patients with ILD in the presence of immune disorders and immunosuppressive therapy. This results in poor control of viral infections following SARS-CoV-2 infection. We aimed to highlight the clinical management of patients with ILD with regard to the adjustment of anti-inflammatory therapy during SARS-CoV-2 infection. Methods: We compared viral clearance, antibody levels, and T-cell immune response between healthy controls and patients with connective tissue disease-related ILD (CTD-ILD) or interstitial pneumonia with autoimmune features (IPAF). Results: Patients with ILD exhibited a higher viral load than the control group (1.58 × 10⁶ vs. 2.37 × 10³ copies/mL, p = 0.018), as well as a significantly lower level of neutralizing antibodies against the wild-type (WT) virus (7.01 vs. 625.6, p < 0.0001) and Omicron BA.5 (7.19 vs. 128.4, p < 0.001). Similarly, a lower virus-specific T-cell (VST) immune response was observed 14 days post-symptom onset in the ILD group (CD4⁺ VSTs: 0.018 vs. 0.082, p = 0.005; CD8⁺ VSTs: 0.0008 vs. 0.047, p = 0.004). The ILD group had no other heightened inflammatory biomarkers compared with the control group. Conclusions: Our study provides novel evidence of the underlying interaction between virus clearance and host immune status and sheds light on the clinical management of patients with ILD with regard to the adjustment of anti-inflammatory therapy during SARS-CoV-2 infection. Full article

Thyroid eye disease (TED) is characterized by autoimmune inflammation and structural remodelling of orbital tissues, which is a consequence of the activation of orbital fibroblasts (OFs). As a result of this activation, the production of hyaluronan (HA) and the proliferation and adipocyte differentiation of OFs are enhanced. Adipogenesis leads to additional accumulation of HA. The aim of this study was to elucidate the molecular weight distribution of HA produced by OFs under basic conditions and after adipogenic stimuli. The concentration and the molecular weight distribution of HA were examined using ELISA and agarose gel electrophoresis, respectively, in TED (n = 3) and non-TED (n = 3) OF cultures. Under adipogenic stimuli, HA production is increased in OFs. In TED OF cultures, which, unlike non-TED OFs, can differentiate into adipocytes, the enhanced proportion of high-molecular-weight (HMW) HA of more than 2000 kDa is responsible for the increased HA concentration in the culture media. In non-TED OF cultures, which contain a negligible number of differentiating cells after adipogenic stimulation, the medium-molecular-weight (MMW) HA fragments from 50 to 1000 kDa also contribute to the enhanced HA content. Increased production of HMW-HA during adipocyte differentiation of TED OFs is responsible for the elevated HA content in the culture media, which may be an important contributor to both connective tissue matrix expansion and edema in the pathogenesis of TED. Full article

Background: Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vasculopathy, autoimmunity, and fibrosis. Due to its low prevalence and heterogeneous clinical presentation, early diagnosis remains challenging, often delaying appropriate treatment. The disease progresses from microvascular dysfunction, manifesting as Raynaud’s phenomenon, to systemic fibrosis affecting multiple organs, including the lungs, gastrointestinal tract, heart, and kidneys. There have been considerable advancements in understanding the pathophysiology of the disease during the last few years and this has already resulted in the improvement of the therapeutic approaches used to control organ-specific manifestations. However, the underlying cause of the disease still remains incompletely elucidated. Methods: Here, we summarize the current knowledge on the SSc pathogenesis. Results: The pathophysiology involves an interplay of chronic inflammation, impaired vascular function, and excessive extracellular matrix deposition, leading to progressive organ damage. Endothelial dysfunction in SSc is driven by immune-mediated injury, oxidative stress, and the imbalance of vasoconstrictors and vasodilators, leading to capillary loss and chronic hypoxia. Autoantibodies against endothelial cells or other toxic factors induce apoptosis and impair angiogenesis, further exacerbating vascular damage. Despite increased angiogenic factor levels, capillary repair mechanisms are defective, resulting in progressive ischemic damage. Dysregulated immune responses involving Th2 cytokines, B cells, and macrophages contribute to fibroblast activation and excessive collagen deposition. Transforming growth factor-beta (TGF-β) plays a central role in fibrotic progression, while fibroblasts resist apoptosis, perpetuating tissue scarring. The extracellular matrix in SSc is abnormally stiff, reinforcing fibroblast activation and creating a self-perpetuating fibrotic cycle. Conclusions: Advances in molecular and cellular understanding have facilitated targeted therapies, yet effective disease-modifying treatments remain limited. Future research should focus on precision medicine approaches, integrating biomarkers and novel therapeutics to improve patient outcomes. Full article

Purpose: The prevalence and phenotype of capillaroscopic abnormalities in patients with autonomic nervous system dysfunction have not yet been investigated. Multiorgan involvement in dysautonomia entails abnormal vasoreactivity. We aim to correlate the diagnosis of autonomic dysfunction with certain clinical manifestations, which may provide prognostic or diagnostic information using a noninvasive technique, i.e., nailfold video capillaroscopy (NVC). Methods: Patients with autonomic nervous system dysfunction were recruited from rheumatology and neurology clinics with voluntary NVC procedures from 31 January 2024 to 10 January 2024, and a comparison with normal controls was performed. Additional recorded information include demographics and diagnoses of autonomic dysfunction types by autonomic testing, including, but not limited to, the following: reflex screen, sweat test, Valsalva maneuver, nerve fiber density, electromyography (EMG), serology, and history of autoimmune diseases. NVC was performed on a total of 27 patients. This study was approved by the Mayo Clinic Institutional Review Board. Results: The autonomic dysfunction group consisted of small-fiber neuropathy (37%), orthostatic hypotension (48%), autonomic neuropathy (30%), limited autonomic neuropathy (7%), postural orthostatic tachycardia syndrome (POTS) (7%), and connective tissue disease (7%), among other types. Patients with autonomic dysfunction had statistically significant increases in microhemorrhages, dilated capillaries, and ramifications when compared to controls. Conclusions: Autonomic dysfunction was associated with statistically significant microvascular abnormalities compared to normal controls with a distinct NVC pattern. There was a statistically significant correlation between age and BMI with microvascular abnormalities. Here, we demonstrate the diagnostic potential of NVC in autonomic dysfunction and advocate for further study of capillary structures in autonomic dysfunction. Full article

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disorder characterized by three main pathological features: microangiopathy, immunological alterations, and excessive synthesis of extracellular matrix (ECM) proteins, leading to fibrosis of the skin and internal organs. Although the etiology of SSc is still unknown, recent studies have revealed the potential role of genetic and epigenetic factors in disease pathogenesis. They are involved in the regulation of cell metabolism, cell hyperactivity, and the accumulation of extracellular matrix proteins. Short endogenous noncoding RNA molecules (microRNAs; miRNAs) negatively regulate gene expression at the posttranscriptional level and play a significant role in disease pathogenesis. Altered miRNA expression in circulation and disease-specific tissues could serve as biomarkers and potential therapeutic targets in SSc. Full article

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by a widespread accumulation of extracellular matrix components leading to fibrosis of the skin and internal organs. Vascular changes occur in all involved tissues and are responsible for several distinctive clinical manifestations of the disease. This review focuses on the usefulness of various diagnostic tools in clinical practice for the early identification of clinical, functional, and/or structural RV impairment in SSc patients at risk of PH. It aims to identify specific causes of RV dysfunction, describe potential differences in outcome measures, and, ultimately, determine different cut-off values compared to subjects with PH not related to SSc. Full article

Idiopathic inflammatory myopathies are rare and complex representatives of systemic connective tissue diseases. Described initially as only two entities, recent advances in molecular and imaging techniques now divide them into many subtypes, each with unique pathogenesis and clinical phenotypes. Dermatomyositis and its juvenile form are the most prevalent subtypes and are characterized by systemic vasculopathy and humoral autoimmunity. Genetic predisposition and environmental triggers initiate immune tolerance breakdown, leading to autoantibody production, complement activation, and tissue damage. Anti-synthetase syndrome primarily affects the lungs, where immune responses to aminoacyl-RNA synthetases drive vasculopathy, lung inflammation, and fibrosis. Immune-mediated necrotizing myopathies are muscle-specific, with autoantibodies inducing fiber necrosis and atrophy. Lastly, sporadic inclusion body myositis is a slowly progressive myopathy in which dysfunctional protein handling and autophagy are more important pathogenic elements than muscle inflammation itself. The expanding body of basic science evidence can be overwhelming, making it challenging to connect pathogenic mechanisms to clinical manifestations. This review aims to address this challenge by presenting recent insights into myositis pathogenesis from a practical perspective, reinforcing the links between basic science and clinical semiology. Full article

Background/Objectives: Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by fibrosis and vascular damage, significantly increasing the risk of heart failure (HF). Methods: This cross-sectional study included 61 SSc patients (92% female, mean age 63 ± 13 years), excluding those with pulmonary arterial hypertension, referred to a tertiary pulmonary hypertension center. HF stages were classified according to updated guidelines. Clinical, echocardiographic, hemodynamic, and functional capacity data were analyzed in relation to HF stages. Results: A total of 48% of patients had pre-symptomatic HF (5% stage A, 43% stage B), while 38% had symptomatic HF (stage C). Advanced HF stages were significantly associated with older age (p = 0.02) and multiorgan involvement (p = 0.045) but not with SSc subtype or autoantibodies. Structural and functional echocardiographic abnormalities were prevalent (77% and 10%, respectively). Markers of elevated ventricular filling pressure such as left atrial volume (p = 0.011) and E/e’ ratio (p = 0.03) correlated with HF severity. Functional impairment was observed with lower 6 min walk test (6MWT) distance (p = 0.017), reduced VO₂ peak (p = 0.015), and increased VE/VCO₂ slope (p = 0.002). Resting pulmonary artery wedge pressure did not correlate with HF stage (p = 0.93). VE/VCO₂ slope and 6MWT were independently associated with HF severity. Conclusions: Preclinical and symptomatic HF are highly prevalent in SSc patients. HF staging was linked to disease severity, age, and cardiovascular risk factors. Functional capacity tests (6MWT and CPET) serve as valuable tools for HF risk stratification. These findings highlight the critical need for comprehensive cardiovascular assessment and targeted management strategies to mitigate HF progression in SSc patients. Full article

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease marked by vascular remodeling, inflammation, and smooth muscle cell proliferation, with limited treatment options focused primarily on symptom management. The multifactorial nature of PAH, encompassing genetic, autoimmune, and connective tissue contributions, complicates its treatment, while irreversible vascular changes, such as fibrosis, remain unaddressed by current therapies. Fundamental research on molecular pathways and targeted delivery systems has paved the way for advanced therapeutic strategies that aim to modify disease progression rather than merely manage symptoms. Nanoparticle-based drug delivery systems, leveraging controlled release and pulmonary targeting, offer a promising avenue to overcome these challenges. Such systems enable precise localization to pulmonary vasculature, minimize systemic side effects, and support emerging approaches like gene therapy and combination treatments. Future research should focus on refining nanoparticle formulations for personalized medicine, optimizing inhalation delivery systems, and integrating multi-target approaches to achieve curative outcomes in PAH. This review explores pathophysiology of PAH, current pharmacological strategies, and innovative nanoparticle-based therapies, emphasizing their potential to transform PAH treatment and address its underlying mechanisms. Full article

Interstitial lung disease (ILD) is a severe complication of certain connective tissue diseases (CTDs) such as systemic sclerosis (SSc), mixed connective tissue disease (MCTD), idiopathic inflammatory myopathies (IIM), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and it is associated with nailfold videocapillaroscopy (NVC) changes and increased morbidity and mortality rates. Early diagnosis is crucial in order to prevent the progression of ILD, prevent respiratory failure and enhance the patient’s overall quality of life. The most common paraclinical investigations are high-resolution computed tomography (HRCT) and functional respiratory tests such as forced vital capacity (FVC) and the diffusing capacity of the lungs for carbon monoxide (DLCO). The most frequent CTD associated with both ILD and NVC changes is systemic sclerosis. The “late” scleroderma pattern was the most common abnormality identified in NVC results in SSc patients. Other autoimmune diseases were also correlated with ILD and NVC changes, especially when the Raynaud phenomenon was present. Low capillary density was associated with the presence and severity of ILD and a reduction in FVC and DLCO. NVC can also differentiate the capillaroscopic changes in some particular types of ILD, such as the usual interstitial pneumonia (UIP) pattern from the non-specific interstitial pneumonia (NSIP) pattern. Nevertheless, further extensive research is necessary in order to establish the diagnostic value of NVC in CTD-ILD in clinical practice. Full article