Search Results (22)

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

Pulmonary arterial hypertension (PAH) is a severe complication associated with connective tissue diseases (CTDs), which is characterized by a significant influence on the patient’s prognosis and mortality. The prevalence of PAH varies depending on the type of CTD. Still, it is highly prevalent in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and primary Sjögren’s syndrome (pSS). Identifying rheumatic disease-specific risk factors is crucial for early diagnosis and intervention. Risk factors for PAH development include specific sociological factors (related to race, gender, and age), clinical features (particularly severe Raynaud’s phenomenon and multiple telangiectasias), cardiological factors (pericarditis and left heart disease), biochemical factors (elevated NT-proBNP and decreased HDL-cholesterol), serological factors (presence of ANA, e.g., anti-U1-RNP or SSA, and antiphospholipid antibodies), and pulmonary factors (interstitial lung disease and decreased DLCO or DLCO/alveolar volume ratio < 70%, FVC/DLCO > 1.6). The analysis of risk factors can be the most useful during the selection of patients at high risk of PAH development. The initial diagnosis of PAH is usually based on transthoracic echocardiography (TTE) and is finally confirmed by right heart catheterization (RHC). Targeted therapies can improve outcomes and include endothelin receptor antagonists, prostacyclin analogs, phosphodiesterase inhibitors, and tailored immunosuppressive treatments. Effective management strategies require a multidisciplinary approach involving rheumatologists, cardiologists, and pulmonologists. The risk stratification and individualized treatment strategies can enhance survival and quality of life in patients with PAH-CTD. Full article

The most serious complications of systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) include lung fibrosis (LF) and pulmonary hypertension (PH). The aim of this study was to find any association between the serological profile and the incidence of these complications. The tested group included 121 persons (87 SSc, 34 MCTD); mean age 55.6 ± 13.4 years. Patients were qualified for the LF presence group based on HRCT. Likelihood of PH was determined using echocardiography. The presence of antinuclear antibodies (ANA) was assessed using indirect immunofluorescence, ANA-profile, sclerosis-profile (using EUROIMMUN kits), and antiphospholipid antibodies (aPL) (using the ELISA method). Distribution of individual antibody types was at a level similar to the previously described groups in the Polish population and differed from the American and African population. A positive correlation was found between LF and the presence of anti-Scl-70 (p = 0.024) antibodies, negative correlation was found between LF and the presence of anti-histone (p = 0.03), anti-centromere A (p = 0.009), anti-centromere B (p = 0.014), and anti-nucleosomes (p = 0.03) antibodies. No correlation between the presence of aPL and the above complications was found. The prevalence of individual antibody types in SSc and MCTD may have ethnic and geographical grounds. Scl-70 antibodies correlate positively with LF. Anti-centromere, anti-histone, and anti-nucleosome antibodies reduce its risk. No correlation between aPL and the occurrence of LF and elevated PH risk was found. Full article

Drug-resistant epilepsy (DRE) affects 20–30% of patients with epilepsy who fail to achieve seizure control with antiseizure medications, posing a significant therapeutic challenge. In this narrative review, we examine the clinical efficacy and safety of the classic ketogenic diet (cKD) and its variants, including the modified Atkins diet (MAD), medium-chain triglyceride diet (MCTD), and low glycemic index treatment (LGIT), in patients with genetically confirmed drug-resistant epilepsy. These diets induce a metabolic shift from glucose to ketones, enhance mitochondrial function, modulate neurotransmitter balance, and exert anti-inflammatory effects. However, genetic factors strongly influence the efficacy and safety of the cKD, with absolute indications including glucose transporter type 1 deficiency syndrome (GLUT1DS) and pyruvate dehydrogenase complex deficiency (PDCD). Preferred adjunctive applications of the KD include genetic epilepsies, such as SCN1A-related Dravet syndrome, TSC1/TSC2-related tuberous sclerosis complex, and UBE3A-related Angelman syndrome. However, because of the risk of metabolic decompensation, the cKD is contraindicated in patients with pathogenic variants of pyruvate carboxylase and SLC22A5. Recent advancements in precision medicine suggest that genetic and microbiome profiling may refine patient selection and optimize KD-based dietary interventions. Genome-wide association studies and multiomics approaches have identified key metabolic pathways influencing the response to the cKD, and these pave the way for individualized treatment strategies. Future research should integrate genomic, metabolomic, and microbiome data to develop biomarker-driven dietary protocols with improved efficacy and safety. As dietary therapies continue to evolve, a personalized medical approach is essential to maximize their clinical utility for genetic epilepsy and refractory epilepsy syndromes. 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

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: The positivity of anti-RNP autoantibodies as biological criteria for the diagnosis of mixed connective tissue disease (MCTD) has recently divided the rheumatology community. Autoantigenicity of the U1-snRNP complex tends to generate multiple autoantibodies against RNP-A, -C and -70 KDa or Sm proteins. The aim of this study is to identify the most informative autoantibodies in clinical practice, in particular, to contribute to differential diagnosis between MCTD and systemic lupus erythematosus (SLE). Methods: Sera from 74 patients positive for anti-RNP autoantibodies were selected over a period of one year of laboratory practice. Autoantibodies directed against extractable nuclear antigen, RNP proteins (A, C, 70 KDa) and 40 kDa fragments of RNP-70 KDa were investigated by using quantitative fluoroenzymatic assay and Western blot analysis. Results: Among the 74 patients, 40 patients were diagnosed with SLE, 20 with MCTD, six with another autoimmune disease, three with SARS-CoV-2 infection, three with cancer and two were healthy. No preferential clinical association of IgG or IgM autoantibodies directed against each of the RNP proteins was found between SLE and MCTD. In contrast, the proportion of autoantibodies directed against the RNP component within the U1-snRNP complex showed a significantly higher RNP index in patients with MCTD than in those with SLE (p = 0.011), with good performance (sensitivity: 69.2%, specificity: 88.9%). Conclusions: The analysis of the proportion of the different autoantibodies directed against the U1-snRNP complex is more informative than the analysis of each autoantibody separately. A follow-up of patients could be informative about the interest of the RNP index as a predictor of disease evolution. Full article

Interstitial lung disease (ILD) frequently complicates mixed connective tissue disease (MCTD) and contributes to increased mortality. We aimed to identify predictors of ILD in MCTD patients. This is a nationwide, multicentre, retrospective study including patients with an adult-onset MCTD clinical diagnosis who met Sharp’s, Kasukawa, Alarcón-Segovia, or Kahn’s diagnostic criteria and had available chest high-resolution computed tomography (HRCT) data. Univariate and multivariate analyses were conducted. We included 57 MCTD patients, with 27 (47.4%) having ILD. Among ILD patients, 48.1% were asymptomatic, 80.0% exhibited a restrictive pattern on pulmonary function tests, and 81.5% had nonspecific interstitial pneumonia on chest HRCT. Gastroesophageal involvement (40.7% vs. 16.7%, p = 0.043) and lymphadenopathy at disease onset (22.2% vs. 3.3%, p = 0.045) were associated with ILD. Binary logistic regression identified lymphadenopathy at disease onset (OR 19.65, 95% CI: 1.91–201.75, p = 0.012) and older age at diagnosis (OR 1.06/year, 95% CI: 1.00–1.12, p = 0.046) as independent ILD predictors, regardless of gender and gastroesophageal involvement. This study is the first to assess a Portuguese MCTD cohort. As previously reported, it confirmed the link between gastroesophageal involvement and ILD in MCTD patients. Additionally, it established that lymphadenopathy at disease onset and older age at diagnosis independently predict ILD in MCTD patients. Full article

Mixed connective tissue disease (MCTD) is a very rare disorder that belongs in the rare and clinically multifactorial groups of diseases. The pathogenesis of MCTD is still unclear. The best understood epigenetic alteration is DNA methylation whose role is to regulate gene expression. In the literature, there are ever-increasing assumptions that DNA methylation can be one of the possible reasons for the development of Autoimmune Connective Tissue Diseases (ACTDs) such as systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The aim of this study was to define the global DNA methylation changes between MCTD and other ACTDs patients in whole blood samples. The study included 54 MCTD patients, 43 SSc patients, 45 SLE patients, and 43 healthy donors (HC). The global DNA methylation level was measured by ELISA. Although the global DNA methylation was not significantly different between MCTD and control, we observed that hypomethylation distinguishes the MCTD patients from the SSc and SLE patients. The present analysis revealed a statistically significant difference of global methylation between SLE and MCTD (p < 0.001), SLE and HC (p = 0.008), SSc and MCTD (p ≤ 0.001), and SSc and HC (p < 0.001), but neither between MCTD and HC (p = 0.09) nor SSc and SLE (p = 0.08). The highest % of global methylation (median, IQR) has been observed in the group of patients with SLE [0.73 (0.43, 1.22] and SSc [0,91 (0.59, 1.50)], whereas in the MCTD [0.29 (0.20, 0.54)], patients and healthy subjects [0.51 (0.24, 0.70)] were comparable. In addition, our study provided evidence of different levels of global DNA methylation between the SSc subtypes (p = 0.01). Our study showed that patients with limited SSc had a significantly higher global methylation level when compared to diffuse SSc. Our data has shown that the level of global DNA methylation may not be a good diagnostic marker to distinguish MCTD from other ACTDs. Our research provides the groundwork for a more detailed examination of the significance of global DNA methylation as a distinguishing factor in patients with MCTD compared to other ACTDs patients. Full article

The detection of antinuclear antibodies is central to the diagnosis and prognosis of systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS) and mixed connective tissue disease (MCTD). Anti-U1-RNP and anti-RNP70 antibodies were assayed in the sera of patients with SLE (n = 114), pSS (n = 54) and MCTD (n = 12). In the SLE group, 34/114 (30%) were anti-U1-RNP positive, and 21/114 (18%) were both anti-RNP70 positive and anti-U1-RNP positive. In the MCTD group, 10/12 (83%) were anti-U1-RNP positive, and 9/12 (75%) were anti-RNP70 positive. Only one individual with pSS was antibody positive (for both anti-U1-RNP and anti-RNP70). All anti-RNP70-positive samples were also anti-U1-RNP positive. Anti-U1-RNP-positive subjects with SLE were younger (p < 0.0001); showed lower concentrations of complement protein 3 (p = 0.03); had lower eosinophil (p = 0.0005), lymphocyte (p = 0.006) and monocyte (p = 0.03) counts; and had accrued less organ damage (p = 0.006) than the anti-U1-RNP-negative SLE patients. However, we observed no significant clinical or laboratory parameter differences between the anti-U1-RNP-positive individuals with/without anti-RNP70 in the SLE group. In conclusion, anti-RNP70 antibodies are not exclusive to MCTD but are rarely detected in pSS and healthy individuals. In SLE, anti-U1-RNP antibodies are associated with a clinical phenotype that resembles MCTD, with hematologic involvement and less damage accrual. Based on our results, the clinical value of subtyping anti-RNP70 in anti-U1-RNP-positive sera appears to be of limited value. Full article

Introduction: We have previously shown that trained-immunity-based vaccines, namely TIbV, significantly reduce the rate of recurrent infections, both of the respiratory tract (RRTI) and urinary tract infections (RUTI) in SAD patients on disease-modifying drugs (DMARDs). Objective: We evaluated the frequency of RRTI and RUTI from 2018 to 2021 in those SAD patients that received TIbV until 2018. Secondarily, we evaluated the incidence and clinical course of COVID-19 in this cohort. Methods: A retrospective observational study was conducted in a cohort of SAD patients under active immunosuppression immunized with TIbV (MV130 for RRTI and MV140 for RUTI, respectively). Results: Forty-one SAD patients on active immunosuppression that were given TIbV up to 2018 were studied for RRTI and RUTI during the 2018–2021 period. Approximately half of the patients had no infections during 2018–2021 (51.2% no RUTI and 43.5% no RRTI at all). When we compared the 3-year period with the 1-year pre-TIbV, RRTI (1.61 ± 2.26 vs. 2.76 ± 2.57; p = 0.002) and RUTI (1.56 ± 2.12 vs. 2.69 ± 3.07; p = 0.010) episodes were still significantly lower. Six SAD patients (four RA; one SLE; one MCTD) with RNA-based vaccines were infected with SARS-CoV-2, with mild disease. Conclusions: Even though the beneficial protective effects against infections of TIbV progressively decreased, they remained low for up to 3 years, with significantly reduced infections compared to the year prior to vaccination, further supporting a long-term benefit of TIbV in this setting. Moreover, an absence of infections was observed in almost half of patients. Full article

Employing cables with strong flexibility and unidirectional restraints to operate a camera platform leads to stability issues for a camera robot with long-span cables considering the cable mass. Cable tensions, which are the constraints for the camera platform, have a critical influence on the stability of the robot. Consequently, this paper focuses on two special problems of minimum cable tension distributions (MCTDs) within the workspace and the cable tension sensitivity analysis (CTSA) for a camera robot by taking the cable mass into account, which can be used to investigate the stability of the robot. Firstly, three minimum cable tension distribution indices (MCTDIs) were proposed for the camera robot. An important matter is that the three proposed MCTDIs, which represent the weakest constraints for the camera platform, can be employed for investigating the stability of the robot. In addition, a specified minimum cable tension workspace (SMCTW) is introduced, where the minimum cable tension when the camera platform is located at arbitrary position meets the given requirement. Secondly, the CTSA model and cable tension sensitivity analysis index (CTSAI) for the camera robot were proposed with grey relational analysis method, in which the influence mechanism and influence degree of the positions of the camera platform relative to cable tensions was investigated in detail. Lastly, the reasonableness of the presented MCTDIs and the method for the CTSA with applications in the stability analysis of the camera robot were supported by performing some simulation studies. Full article

The aim of this study was to develop a Croatian Delphi-based expert consensus for screening interstitial lung disease (ILD) associated with connective tissue disease (CTD). A systematic literature review was conducted on risk factors for the development of ILD, prevalence and incidence of ILD, diagnostic and screening methods for ILD, and prognosis of ILD in idiopathic inflammatory myopathy (IIM), mixed connective tissue disease (MCTD), primary Sjögren’s syndrome (pSS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) were performed. Based on the evidence found, experts developed questionnaires for screening and monitoring ILD in each CTD, which were provided via an online survey. Following the electronic survey, two screening algorithms were developed based on the consensus opinions. The detection strategy for ILD included high-resolution computed tomography (HRCT) in addition to pulmonary function testing for IIM, MCTD, and SSc. and pulmonary function testing for newly diagnosed pSS, RA and SLE. However, in patients with identified risk factors for ILD HRCT, these tests should also be performed. A screening strategy for early identification of patients with various CTD-ILD was first developed by a multidisciplinary team of rheumatologists, pulmonologists, and radiologists to identify early CTD patients at risk of ILD, a severe extra-articular manifestation of CTD. Full article

In a dual-bridge series resonant converter (DBSRC) working at a high switching frequency, the dead-time effect is a serious issue. When the minimum current trajectory (MCT) method is applied, the inductor current cannot be minimized due to the dead-time effect, and the range of the soft switching is reduced. Considering the dead-time, this paper first presents a theoretical analysis of the transmission power and the soft-switching characteristics based on the fundamental harmonic approximation (FHA) approach. Then, a minimum current trajectory method considering the dead-time (MCT-d) is proposed to achieve the minimum inductor current by compensating for the dead-time. This method can extend the soft-switching range as well. Finally, the experimental results validate the theoretical analysis and the improvement of the converter’s efficiency. Full article

Background: The recently published 2019 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for systemic lupus erythematosus (SLE) were developed to increase the reliability and identification of SLE, especially in early disease. With the emergence of several new drugs for SLE, identifying and treating patients early are more important than ever. Methods: Data of 446 SLE patients evaluated in our center between 1996–2019 and 226 controls with other autoimmune diseases evaluated between 2001–2022 were retrospectively analyzed. The sensitivity and specificity of the 2019 ACR/EULAR criteria were compared to the 2012 SLICC and the 1997 ACR criteria. Results: The 2019 ACR/EULAR criteria showed very good sensitivity (86.6%) compared to the 1997 ACR criteria (76.7%), p < 0.001, with a trend toward significance compared to the 2012 SLICC criteria (83.6%), p = 0.072. Their sensitivity remained high (87.6%) in patients with a short disease duration. The specificity of the 2019 ACR/EULAR criteria (91.2%) was statistically lower than the 2012 SLICC (96.0%) and 1997 ACR criteria (95.1%), p = 0.007 and p = 0.012, respectively, but still had a very high value. A total of 22 controls (9.7%) fulfilled at least one set of criteria (15 patients with MCTD, 5 with UCTD, and 2 with SSc). Conclusion: In this large real-life cohort, the 2019 ACR/EULAR criteria had very good performance compared to the 2012 SLICC and 1997 ACR criteria. Full article