Introduction Hypereosinophilic syndrome (HES) is a group of a rare diseases characterized by marked eosinophilia in blood or tissue and eosinophil-related clinical manifestations. Benralizumab is a ...humanized, monoclonal antibody against interleukin 5 (IL-5) receptor a, which is expressed on human eosinophils. Case study Here, we present the case of a patient with severe HES in whom treatment with benralizumab, an anti-IL-5 receptor monoclonal antibody, was initiated 6 months ago. Prior to benralizumab administration, the patient was treated with glucocorticoids (GS) and mepolizumab. However, instead of the applied treatment and normal level of peripheral eosinophils the patient presented with fluctuating lower respiratory tract symptoms and recurrent exacerbations of HES. Results Treatment with benralizumab (30 mg s.c. every 4-6 weeks) was started, resulting in significant improvement of respiratory signs and symptoms, normalization of eosinophil count and significant reduction of the methylprednisolone dose (after 5 doses of benralizumab administration). No substantial side effects have been noted during treatment and 6-month follow-up. Conclusions We argue that in the severe and relapsing course of HES, rescue treatment with benralizumab should be taken into account, particularly in cases of relative inefficacy of GS and mepolizumab.
Tumor necrosis factor (TNF)-α is a proinflammatory cytokine that plays an important role in the pathogenesis of autoimmune diseases. The aim of the study was to establish an association between TNF-α ...promoter variability and systemic sclerosis (SSc). The study included 43 SSc patients and 74 controls. Four single nucleotide polymorphisms (rs361525, rs1800629, rs1799724, and rs1799964) located at the promoter of the TNFA gene were genotyped using commercially available TaqMan allelic discrimination assays with real-time PCR. The rs1799724 allele was associated with an increased SSc susceptibility (
= 0.028). In turn, none of the polymorphisms studied were related to the clinical and laboratory parameters of SSc patients, except for a higher prevalence of anti-Ro52 antibodies in the AG rs1800629 genotype in comparison to GG carriers (
= 0.04). Three of four cancer patients had both CT rs1799964 and AG rs361525 genotypes; thus, both of them were related to the increased risk of cancer, as compared to the TT (
= 0.03) and GG carriers (
= 0.0003), respectively. The TNFA C rs1799724 variant is associated with an increased risk of SSc, while the CT rs1799964 and AG rs361525 genotypes might enhance cancer susceptibility in SSc patients, although large observational and experimental studies are needed to verify the above hypothesis.
Lung ultrasound (LUS) is an increasingly popular imaging method in clinical practice. It became particularly important during the COVID-19 pandemic due to its mobility and ease of use compared to ...high-resolution computed tomography (HRCT). The objective of this study was to assess the value of LUS in quantifying the degree of lung involvement and in discrimination of lesion types in the course of COVID-19 pneumonia as compared to HRCT analyzed by the artificial intelligence (AI).
This was a prospective observational study including adult patients hospitalized due to COVID-19 in whom initial HRCT and LUS were performed with an interval < 72 h. HRCT assessment was performed automatically by AI. We evaluated the correlations between the inflammation volume assessed both in LUS and HRCT, between LUS results and the HRCT structure of inflammation, and between LUS and the laboratory markers of inflammation. Additionally we compared the LUS results in subgroups depending on the respiratory failure throughout the hospitalization.
Study group comprised 65 patients, median 63 years old. For both lungs, the median LUS score was 19 (IQR-interquartile range 11-24) and the median CT score was 22 (IQR 16-26). Strong correlations were found between LUS and CT scores (for both lungs r = 0.75), and between LUS score and percentage inflammation volume (PIV) (r = 0.69). The correlations remained significant, if weakened, for individual lung lobes. The correlations between LUS score and the value of the percentage consolidation volume (PCV) divided by percentage ground glass volume (PGV), were weak or not significant. We found significant correlation between LUS score and C-reactive protein (r = 0.55), and between LUS score and interleukin 6 (r = 0.39). LUS score was significantly higher in subgroups with more severe respiratory failure.
LUS can be regarded as an accurate method to evaluate the extent of COVID-19 pneumonia and as a promising tool to estimate its clinical severity. Evaluation of LUS in the assessment of the structure of inflammation, requires further studies in the course of the disease.
The study has been preregistered 13 Aug 2020 on clinicaltrials.gov with the number NCT04513210.
Natural killer (NK) cells plays a pivotal role in the control of viral infections, and their function depend on the balance between their activating and inhibitory receptors. The immune dysregulation ...observed in COVID-19 patients was previously associated with downregulation of NK cell numbers and function, yet the mechanism of inhibition of NK cell functions and the interplay between infected cells and NK cells remain largely unknown.
In this study we show that SARS-CoV-2 infection of airway epithelial cells can directly influence NK cell phenotype and functions in the infection microenvironment. NK cells were co-cultured with SARS-CoV-2 infected epithelial cells, in a direct contact with A549
cell line or in a microenvironment of the infection in a 3D ex vivo human airway epithelium (HAE) model and NK cell surface expression of a set of most important receptors (CD16, NKG2D, NKp46, DNAM-1, NKG2C, CD161, NKG2A, TIM-3, TIGIT, and PD-1) was analyzed.
We observed a selective, in both utilized experimental models, significant downregulation the proportion of CD161 (NKR-P1A or KLRB1) expressing NK cells, and its expression level, which was followed by a significant impairment of NK cells cytotoxicity level against K562 cells. What is more, we confirmed that SARS-CoV-2 infection upregulates the expression of the ligand for CD161 receptor, lectin-like transcript 1 (LLT1, CLEC2D or OCIL), on infected epithelial cells. LLT1 protein can be also detected not only in supernatants of SARS-CoV-2 infected A549
cells and HAE basolateral medium, but also in serum of COVID-19 patients. Finally, we proved that soluble LLT1 protein treatment of NK cells significantly reduces
the proportion of CD161+ NK cells,
the ability of NK cells to control SARS-CoV-2 infection in A549
cells and
the production of granzyme B by NK cells and their cytotoxicity capacity, yet not degranulation level.
We propose a novel mechanism of SARS-CoV-2 inhibition of NK cell functions via activation of the LLT1-CD161 axis.
Percutaneous coronary intervention (PCI) is an effective method for the treatment ofcoronary artery disease (CAD) that allows for a short hospital stay and fast recovery. It has been shown that PCI ...is a predictor of nonattendance at cardiac rehabilitation and correlates with poor adherence to lifestyle changes.
The study was conducted to evaluate the influence of education offered during PCI‑related hospitalization on knowledge, awareness, and prevalence of self‑reported risk factors for CAD.
We collected data using a self‑designed 56‑item questionnaire. Questions assessed the knowledge of CAD risk factors and the level of their control. The maximal knowledge score was 31 points and the maximal control score, 15 points.
The study group consisted of 200 consecutive patients undergoing PCI. Patients with a history of PCI performed at least 8 weeks prior to their current hospitalization were included in the prior‑PCI group (64%), whereas the pre‑PCI group comprised patients with no history of revascularization (36%). The median (interquartile range IQR) knowledge score was 19 (12.5-23) points in the pre‑PCI and 21 (12.5-24) points in the prior‑PCI group (P = 0.35). The median (IQR) risk control score was 5 (4.5-7) points in the pre‑PCI and 6 (4-8) points in the prior‑PCI group (P = 0.4). There was no correlation between the level of knowledge and the actual prevalence of CAD risk factors. We found that 50% of the prior‑PCI patients did not attend any rehabilitation, which correlated with poor control of CAD risk factors (P = 0.001).
Currently used models of postprocedural education do not have an adequate effect on patient knowledge and do not bring recommended lifestyle changes.
Sarcoidosis is a multisystem inflammatory granulomatous disease of unknown cause that most commonly affects lungs and lymph nodes, with frequent yet asymptomatic cardiac involvement. The ...epidemiologically associated cardiovascular risk suggests an underlying prothrombotic state and endothelial dysfunction, currently understudied in the available literature. Therefore, we aimed to investigate prothrombotic plasma properties together with selected echocardiographic and laboratory biomarkers of cardiovascular injury in that disease. N = 53 patients with pulmonary sarcoidosis in clinical remission and N = 66 matched controls were assessed for inflammatory and endothelial injury biomarkers, plasma thrombin generation profile, and echocardiographic and lung function parameters. Sarcoidosis cases had impaired systolic and diastolic left ventricular function, higher concentrations of inflammatory markers, D-dimer and factor VIII activity compared to the controls. The coexistence of extrapulmonary disease was associated with elevated circulating vascular cell adhesion molecule 1, while cases with hypercalcemia had higher thrombomodulin concentration. Sarcoidosis was characterized by the unfavorably altered thrombin generation profile, reflected by the 16% higher endogenous thrombin potential (ETP), 24% increased peak thrombin concentration, and 12% shorter time to thrombin peak in comparison to the control group. ETP was higher in cases with proxies of pulmonary restriction, extrapulmonary-extracutaneous manifestation, and need for corticosteroids use. Despite the clinical remission, sarcoidosis is related to prothrombotic plasma properties and signs of endothelial injury, likely contributing to the higher risk of cardiovascular events. In addition, subclinical cardiac involvement may play an additional role, although further clinical and experimental studies are needed to verify these findings.
Asthma heterogeneity complicates the search for targeted treatment against airway inflammation and remodeling. We sought to investigate relations between eosinophilic inflammation, a phenotypic ...feature frequent in severe asthma, bronchial epithelial transcriptome, and functional and structural measures of airway remodeling. We compared epithelial gene expression, spirometry, airway cross-sectional geometry (computed tomography), reticular basement membrane thickness (histology), and blood and bronchoalveolar lavage (BAL) cytokines of
= 40 moderate to severe eosinophilic (EA) and non-eosinophilic asthma (NEA) patients distinguished by BAL eosinophilia. EA patients showed a similar extent of airway remodeling as NEA but had an increased expression of genes involved in the immune response and inflammation (e.g.,
), reactive oxygen species generation (
,
), cell activation and proliferation (
), cargo transporting (
,
), and tissue remodeling (
,
,
), and a lower expression of genes involved in epithelial integrity (e.g.,
) and histone acetylation (
). Genes co-expressed in EA were involved in antiviral responses (e.g.,
), cell migration (
,
), cell adhesion (
), epithelial-mesenchymal transition (
), and airway hyperreactivity and remodeling (
,
), and several were linked to asthma in genome- (e.g.,
,
) or epigenome-wide association studies (
,
,
,
). Signaling pathways inferred from the co-expression pattern were associated with airway remodeling (e.g., TGF-β/Smad2/3, E2F/Rb, and Wnt/β-catenin).
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