A proteasome, a multicatalytic protein complex, is a central particle of the ubiquitin-proteasome proteolytic pathway in all eukaryotic cells. Through the degradation of most intracellular proteins, ...proteasomes play a significant role in cell processes, such as cell cycle and division, posttranslational protein quality control, cell signaling, and apoptosis. Therefore, the ubiquitin-proteasome system is necessary to ensure the normal functioning of cells and an organism. The associations between alterations in the ubiquitin-proteasome pathway and the development of various autoimmune, neurodegenerative, inflammatory and other diseases in humans have been established. Moreover, the findings of some studies suggest that proteasomes may participate in the pathogenesis of asthma through the regulation of the nuclear factor kappa B signaling pathway. Recently, much attention has been given to the associations between genes encoding the proteasome and their polymorphism, and various diseases. Associations between some proteasomal genes and myocardial infarction, type 2 diabetes mellitus, and other diseases have already been established. However, the results are inconclusive or conflicting and need further clarification.
Lithuania belongs to the group of countries with a high-incidence of tuberculosis (TB). Some scientific studies show that the interferon-gamma release assay is more accurate and correlates more ...highly with TB exposure as compared to the tuberculin skin test (TST). This study aimed at comparing the efficacy between the T SPOT TB and TST for diagnosing TB among Lithuanian adults.
Individuals with diagnosed TB, healthcare workers with known risk for TB and individuals without any known risk for TB underwent clinical examinations, interviews about their history of TB exposure and chest radiography. Then the TST and the T SPOT TB were performed on patients.
A positive T SPOT TB was more common in the group with diagnosed TB compared to healthcare workers and the low risk for TB groups (97.5%, 36.4%, and 0%, respectively, P<0.01). Positive TST results did not differ between the groups with diagnosed TB and the healthcare workers (92.5% vs. 95.5%, P>0.05). Agreement between TST and T SPOT TB was poor (kappa 0.14, P>0.05). T SPOT TB had higher specificity and sensitivity compared to TST (area under the ROC 0.9±0.04, P<0.01, vs. 0.5±0.06, P>0.05).
The T SPOT TB showed greater accuracy in diagnosing TB than TST did. Positive T SPOT TB result but not the TST was more common in patients with diagnosed TB.
Proteomic studies of respiratory disorders have the potential to identify protein biomarkers for diagnosis and disease monitoring. Utilisation of sensitive quantitative proteomic methods creates ...opportunities to determine individual patient proteomes. The aim of the current study was to determine if quantitative proteomics of bronchial biopsies from asthmatics can distinguish relevant biological functions and whether inhaled glucocorticoid treatment affects these functions.
Endobronchial biopsies were taken from untreated asthmatic patients (n = 12) and healthy controls (n = 3). Asthmatic patients were randomised to double blind treatment with either placebo or budesonide (800 μg daily for 3 months) and new biopsies were obtained. Proteins extracted from the biopsies were digested and analysed using isobaric tags for relative and absolute quantitation combined with a nanoLC-LTQ Orbitrap mass spectrometer. Spectra obtained were used to identify and quantify proteins. Pathways analysis was performed using Ingenuity Pathway Analysis to identify significant biological pathways in asthma and determine how the expression of these pathways was changed by treatment.
More than 1800 proteins were identified and quantified in the bronchial biopsies of subjects. The pathway analysis revealed acute phase response signalling, cell-to-cell signalling and tissue development associations with proteins expressed in asthmatics compared to controls. The functions and pathways associated with placebo and budesonide treatment showed distinct differences, including the decreased association with acute phase proteins as a result of budesonide treatment compared to placebo.
Proteomic analysis of bronchial biopsy material can be used to identify and quantify proteins using highly sensitive technologies, without the need for pooling of samples from several patients. Distinct pathophysiological features of asthma can be identified using this approach and the expression of these features is changed by inhaled glucocorticoid treatment. Quantitative proteomics may be applied to identify mechanisms of disease that may assist in the accurate and timely diagnosis of asthma.
ClinicalTrials.gov registration NCT01378039.
The pattern of contact sensitization among patients with chronic leg ulcers depends on the local practice of wound treatment along with demographic and clinical confounders. The study was aimed at ...revealing the associations between chronic leg ulcers and contact sensitization.
Between 2006 and 2008, 35 patients with chronic leg ulcers and surrounding dermatitis and 59 patients with contact dermatitis of the lower leg or foot were prospectively recruited at the Department of Skin and Venereal Diseases, Lithuanian University of Health Sciences. Demographic and clinical data were collected in accordance with the "minimal data set" of the European Surveillance System on Contact Allergy. Patch testing was performed with the allergens of the European baseline series.
At least one positive patch test reaction was found in 28 (80%) of the patients with chronic leg ulcers and in 24 (41%) of the patients with dermatitis of the lower leg or foot (P<0.001). Sensitization to some of the most common allergens, namely colophony, Myroxylon pereirae resin, and methyldibromo glutaronitrile, was prevalent in both the groups of patients, whereas sensitization to benzocaine, p-phenylenediamine, and lanolin alcohol was associated with the presence of chronic leg ulcers. Benzocaine was found to be the leading allergen among patients with chronic leg ulcers (positive patch test reactions in 34.4% of the patients).
Contact sensitization to benzocaine, p-phenylenediamine, and lanolin was found to be associated with the presence of chronic leg ulcers.
Asthma is divided into various distinct phenotypes on the basis of clinical characteristics, physiological findings, and triggers, and phenotyping is usually performed in a hypothesis-driven ...univariate manner. However, phenotyping can also be performed using computer algorithms to evaluate hypotheses-free relationships among many clinical and biological characteristics. We aimed to identify asthma phenotypes based on multiple demographic, clinical, and immunological characteristics.
Cluster analysis in R v3.5.0 was performed using asthma patient data. A total of 170 adult patients with asthma (diagnosed according to the GINA recommendations) were recruited to the study. All patients completed questionnaires about their smoking history and underwent physical examination, spirometry, skin-prick test, blood sample collection to evaluate peripheral blood cell counts and serum IgE, periostin, and interleukin (IL)-33 levels, as well as body mass index measurements. Data normality was checked with histograms and QQ plots. Hierarchical clustering was performed using Ward's linkage with Ward's clustering criterion. The optimal number of clusters was validated using the Dunn criterion as well as by comparing different clustering algorithms using the clValid package.
Three clusters characterizing asthma phenotypes were identified: (1) early-onset, highly atopic, and eosinophilic asthma associated with male sex and high levels of IL-33 and periostin; (2) late-onset, eosinophilic asthma associated with female sex and low levels of IL-33 and periostin; and (3) late-onset, obese, neutrophilic asthma associated with female sex, persistent airway obstruction, and very low IL-33 and periostin levels.
Lithuania is a country with a high incidence of tuberculosis (TB), despite a high coverage with bacille Calmette-Guerin (BCG) vaccination. Until now the only method used to detect latent TB infection ...was the tuberculin skin test (TST). However, TST may have a cross reactivity to the BCG vaccine and to environmental mycobacteria. The aim of this study was to conduct assessments of the diagnostic accuracy of the T-cell based test (T SPOT TB) for TB in children who had previously been BCG vaccinated and compare these with the results of the TST.
Between January 2005 and February 2007, children with bacteriologically confirmed TB, children having contacts with a case of infectious pulmonary TB and children without any known risk for TB were tested with both the TST and T SPOT TB.
The TST and T SPOT TB tests were positive for all patients in the "culture-confirmed TB" group. Whereas, in the "high risk for TB" group, the TST was positive for 60%, but the T SPOT TB test, only for 17.8%. Meanwhile the results for the "low risk for TB" group were 65.4% and 9.6%, respectively. A correlation between the TST and T SPOT TB was obtained in the "culture-confirmed TB" group where the TST > or =15 mm (r = 0.35, p < 0.001).
The T-cell based method is more objective than the TST for identifying latent TB infection in children who had been previously BCG vaccinated. This method could be useful in countries like Lithuania where there is a high incidence of TB despite a high coverage with BCG vaccination. It may also help to avoid unnecessary chemoprophylaxis when TST reactions are false-positive.
IL‐33 is a recently discovered cytokine which plays an important role in asthma pathogenesis.
Aim
To evaluate serum IL‐33 in patients with asthma and healthy controls, and to evaluate the association ...of IL‐33 with different asthma phenotypes.
Methods
Patients with asthma (n = 115) and healthy subjects (n = 85) were included in the study. Subjects with asthma were divided into groups according to their phenotype: allergic/non‐allergic, eosinophilic/non‐eosinophilic, obese/non‐obese and severity according to GINA (mild, moderate and severe). The concentration of IL‐33 in serum was measured by standardized enzyme‐linked immunosorbent assay.
Results
The level of IL‐33 was significantly higher in patients with asthma when compared to healthy subjects (672.73 ± 104.47 pg/mL vs 268.52 ± 27.56 pg/mL, P < 0.05). IL‐33 was also higher in the allergic asthma group patients when compared to non‐allergic asthmatics (844.61 ± 152.08 pg/mL vs 369.56 ± 77.94 pg/mL, P < 0.05). There was a significantly higher serum IL‐33 level in the eosinophilic asthma group when compared to the group of non‐eosinophilic asthma patients (1001.10 ± 199.11 pg/mL vs 337.49 ± 72.68 pg/mL, P < 0.01). We did not find a significant difference in serum IL‐33 level between different asthma severity groups, obese and non‐obese asthmatics.
Conclusion
IL‐33 is increased in asthma patients, particularly in some phenotypes: allergic asthma and eosinophilic asthma.
The aim of this study was to establish C-reactive protein (CRP) levels in serum of patients with lung cancer and chronic obstructive pulmonary disease (COPD) and evaluate the associations of CRP ...levels with clinicopathological characteristics.
In total, 140 persons were included in the study: 43 patients with lung cancer, 34 patients with lung cancer and COPD, 42 patients with COPD, and 21 healthy subjects. CRP analysis was performed with a serum protein analyzer using commercially available high-sensitivity reagent kits.
The C-reactive protein levels were significantly higher in the lung cancer patients with or without COPD compared with the COPD patients or the control group (20.42±1.95 and 22.49±2.31 vs. 8.37±0.91 and 2.49±0.47 mg/L, respectively; P<0.01). The patients with advanced lung cancer had higher CRP levels compared with the patients suffering from early stage lung cancer (23.11±1.72 vs. 14.59±2.23 mg/L, P<0.01). The CRP levels were significantly higher in the patients with early stage lung cancer compared with the COPD patients (14.59±2.23 mg/L vs. 8.37±0.91 mg/L, P<0.05). No association was found between CRP and histology, lung function, and smoking status in the patients with lung cancer.
Chronic inflammation plays an important role in both diseases: lung cancer and COPD. However, it seems that inflammation is more pronounced in patients with lung cancer, as the CRP levels were significantly higher in these patients than other groups.
Asthma is one of the most common chronic respiratory diseases with an increasing prevalence and financial burden worldwide. This disease affects individuals in all countries and all ethnic groups; ...however, prevalence rates of asthma have been reported to vary significantly between different regions. To understand the origin of asthma and to manage it effectively, it is necessary to analyze the genetic and environmental factors that cause these geographic differences. Therefore, we aimed to review published data from the investigations of asthma patients in Eastern Europe, represented by Latvia and Lithuania, and of patients from Eastern Asia represented by Taiwan. We hope that some of the common factors can be identified and different variants can be compared among these three countries for development of a new strategy to prevent childhood asthma.
Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic ...delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.
We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.
We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.
Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.
An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.
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