The influence of sublingual immunotherapy on several parameters of immunological response in children suffering from atopic asthma and allergic rhinitis depending on asthma features

Wstęp: Kliniczna skuteczność immunoterapii podjęzykowej została już gruntowanie potwierdzona i udokumentowana. Badano również jej wpływ na układ odpornościowy chorych na astmę oskrzelową. J ednak do tej pory nie wyjaśniono zależności pomiędzy występowaniem alergii wieloważnej, współwystępowaniem innych chorób alergicznych i stopniem terapii astmy a wpływem prowadzonej alergenowo-swoistej immunoterapii podjęzykowej. Celem niniejszej pracy była ocena wpływu rocznej immunoterapii podjęzykowej na wybrane parametry odpowiedzi immunologicznej w zależności od cech osobniczych i klinicznych cech choroby u pacjentów chorych na astmę i alergiczny nieżyt nosa.Materiał i metody: Do badania zakwalifikowano 25 dzieci w wieku 8,1 ± 3,1 roku (5–15 lat), 21 chłopców i 4 dziewczynki, chorych na astmę oskrzelową i alergiczny nieżyt nosa z alergiami poliwalentnymi sezonowymi i niesezonowymi, które były zakwalifikowane do alergenowo-swoistej immunoterapii podjęzykowej. Odsetek limfocytów pomocniczych Th1 i Th2, ekspresję antygenu Bcl-2 w limfocytach T oraz aktywację bazofilów pod wpływem swoistych alergenów (zawiesiny antygenów roztoczy kurzu domowego i/lub pyłków traw do testów skórnych) badano metodą cytometrii przepływowej. Z ależności pomiędzy badanymi parametrami oceniano dokładnym testem Fishera.Wyniki: Nie zaobserwowano istotnych zależności pomiędzy wpływem immunoterapii podjęzykowej na układ odpornościowy pacjentów a wiekiem, występowaniem alergii wieloważnej, stopniem terapii astmy i współwystępowaniem innych chorób alergicznych. Wzrost odsetka limfocytów pomocniczych Th1 pod wpływem immunoterapii podjęzykowej obserwowano nieco częściej u dzieci uczulonych na więcej niż 3 alergeny niż u pozostałych.Wnioski: Na podstawie badań przeprowadzonych przez autorów pracy nie można wskazać żadnej grupy pacjentów, u których można się spodziewać silniejszej mobilizacji układu odpornościowego jako odpowiedzi na prowadzoną immunoterapię podjęzykową u dzieci chorych na astmę i alergiczny nieżyt nosa. Wzrost odsetka limfocytów pomocniczych Th1 może występować częściej u dzieci z alergią poliwalentną.Introduction: The clinical efficacy of sublingual immunotherapy (SLIT) has already been proven and is known to be high. Its influence on the immunological system of patients suffering from bronchial asthma was also examined. However, it is still unclear how the polysensitisation, coexistence of other atopic disease and asthma treatment step influence the response to treatment with specific immunotherapy. Herein we evaluate the impact of one-year SLIT on selected markers of immunological response depending on different individual and clinical factors of children suffering from atopic asthma and allergic rhinitis.Material and methods: Twenty-five patients aged 8.1 ± 3.1 years (range 5–15 years), 21 boys and 4 girls, suffering from asthma and allergic rhinitis with polysensitisation to seasonal and non-seasonal allergens, shortlisted for SLIT, were included in the study. Th1 cell and Th2 cell percentages, Bcl-2 expression in T cells, and basophil activation after allergen challenge (house dust mite and/or grass pollen antigen in solution used for skin prick tests) in peripheral blood were measured using flow cytometry. The association between clinical features of asthma and the influence of SLIT on immunological parameters was evaluated with exact Fisher test.Results: No association between the influence of one-year sublingual immunotherapy on immunological system and patients’ age, polysensitisation, asthma treatment step, or coexistence of any other atopic diseases was observed. However, an increase of the Th1 percentage in children sensitised against more than three allergens was found more often (at the limit of statistical significance) than in the group of children sensitised against three or less allergens.Conclusions: Based on our results, we cannot point to any subgroup isolated in the study, in which the response of the immunological system to sublingual immunotherapy is more satisfactory than any other. Nevertheless, the increase of Th1 cells may be more specific for polysensitised children

Rh negativity seems to predispose to a milder COVID-19 course

Introduction: Infection with the SARS-CoV-2 virus can lead to the development of COVID-19. Currently, more than 700 million people worldwide have been diagnosed with COVID-19, of which nearly 7 million have died from the severe course of the disease. Recent reports suggest that patients with blood group A are most at risk of developing COVID-19, and people with natural anti-A antibodies (especially those with blood type 0) have a milder course of the disease. This study aimed to assess the humoral response to infection with SARS-CoV-2 depending on the patient’s blood type. Material and methods: The study group consisted of 147 patients with confirmed previous COVID-19 (convalescents) and 147 individuals who declared no previous infection with SARS-CoV-2. All enrolled subjects were blood donors registered at Regional Blood Center. The concentration of SARS-CoV-2 anti-nucleocapsid antibodies was determined in the serum of the patients using the Elecsys Anti-SARS-CoV-2 test. The blood group was determined by a manual method using anti-A, anti-B, and anti-D monoclonal sera and A, B, and 0 standard red blood cells (RBC). Results and conclusions: Based on anti-SARS-CoV-2 detection 68 people who denied contact with SARS-CoV-2 had previous asymptomatic infection. Blood type distribution differed between the asymptomatic convalescents and the declared convalescents, p = 0.0013. People with Arh–, BRh+, BRh–, and 0Rh– blood type were more often asymptomatically infected. Moreover, the Rh- subjects more often didn’t know about the previous infection than those with Rh+, p = 0.0012. It seems that subjects with Rh– blood type have a significantly milder course of disease than Rh+

The Influence of Deterioration of Kidney Function on the Diagnostic Power of Laboratory Parameters Used in the Prognostic Classification of AL Amyloidosis

There is a possibility that renal dysfunction may potentially reduce the diagnostic power of the laboratory parameters Tn, NT-proBNP and sFLC levels, used in the current prognostic classification of AL amyloidosis and the diagnosis of heart involvement by amyloid. In this study, the impact of lowering the eGFR value on the usefulness of these parameters in the prognosis and diagnosis of the presence of amyloid in the myocardium was assessed in a group of 71 patients with newly diagnosed primary amyloidosis. The assessment of diagnostic power of laboratory parameters was performed on the entire study group, and in the ranges of eGFR ≥ 60 and < 60 mL/min/1.73 m2. It has been proven that, with a decrease in the eGFR value, the concentrations of NT-proBNP and the κ uninvolved light chains increase significantly (p < 0.001). To assess the diagnostic power of laboratory parameters used in the diagnosis of myocardial involvement in patients with AL amyloidosis, an ROC analysis was performed. The highest values of AUC were obtained for the NT-proBNP concentration (AUC = 0.906). The lowest values of the AUC and Youden’s index were obtained for the dFLC values (AUC = 0.723), and involved κ FLC concentration (AUC = 0.613). For all compared parameters, the smallest values of the AUC were obtained for eGFR (<60 mL/min/1.73 m2). It seems that the most suitable cardiac parameter used in the prognostic classification of AL amyloidosis, independent of renal function, is TnI. It should be noted that a concentration of involved λ chains hada higher diagnostic power to assess the heart involvement, compared to the routinely used “cardiac parameters”, TnI and NT-proBNP. It can therefore be an additional parameter used to assess the presence of amyloid in the myocardium. A decrease in eGFR value influenced the change in the diagnostic cut-off points of the most analyzed laboratory parameters. Finally, it is concluded that lowering the eGFR value reduces the utility of laboratory parameters used in the prognostic classification of AL amyloidosis

Long COVID Definition, Symptoms, Risk Factors, Epidemiology and Autoimmunity: A Narrative Review

The virus called SARS-CoV-2 emerged in 2019 and quickly spread worldwide, causing COVID-19. It has greatly impacted on everyday life, healthcare systems, and the global economy. In order to save as many lives as possible, precautions such as social distancing, quarantine, and testing policies were implemented, and effective vaccines were developed. A growing amount of data collected worldwide allowed the characterization of this new disease, which turned out to be more complex than other common respiratory tract infections. An increasing number of convalescents presented with a variety of nonspecific symptoms emerging after the acute infection. This possible new global health problem was identified and labelled as long COVID. Since then, a great effort has been made by clinicians and the scientific community to understand the underlying mechanisms and to develop preventive measures and effective treatment. The role of autoimmunity induced by SARS-CoV-2 infection in the development of long COVID is discussed in this review. We aim to deliver a description of several conditions with an autoimmune background observed in COVID-19 convalescents, including Guillain-Barré syndrome, antiphospholipid syndrome and related thrombosis, and Kawasaki disease highlighting a relationship between SARS-CoV-2 infection and the development of autoimmunity. However, further studies are required to determine its true clinical significance

Variations in Magnesium Concentration Are Associated with Increased Mortality: Study in an Unselected Population of Hospitalized Patients

Dysmagnesemia is a serious disturbance of microelement homeostasis. The aim of this study was to analyze the distribution of serum magnesium concentrations in hospitalized patients according to gender, age, and result of hospitalization. The study was conducted from February 2018 to January 2019 at the Central Clinical Hospital in Warsaw. Laboratory test results from 20,438 patients were included in this retrospective analysis. When a lower reference value 0.65 mmol/L was applied, hypermagnesemia occurred in 196 patients (1%), hypomagnesemia in 1505 patients (7%), and normomagnesemia in 18,711 patients (92%). At a lower reference value of 0.75 mmol/L, hypomagnesemia was found in 25% and normomagnesemia in 74% of patients. At a lower reference value of 0.85 mmol/L, hypomagnesemia was found in 60% and normomagnesemia in 39% of patients. Either hypo- or hyper-magnesemia was associated with increased risk of in-hospital mortality. This risk is the highest in patients with hypermagnesemia (40.1% of deaths), but also increases inversely with magnesium concentration below 0.85 mmol/L. Serum magnesium concentration was not gender-dependent, and there was a slight positive correlation with age (p < 0.0001, r = 0.07). Large fluctuations in serum magnesium level were associated with increased mortality (p = 0.0017). The results indicate that dysmagnesemia is associated with severe diseases and generally severe conditions. To avoid misdiagnosis, an increase of a lower cut-off for serum magnesium concentration to at least 0.75 mmol/L is suggested

Dysmagnesemia Is the Most Common Disturbance of the Calcium–Magnesium–Phosphorous Balance among Older Hospitalized People in Warsaw

The elderly are at great risk of developing life-threatening disturbances in calcium–magnesium–phosphate homeostasis because of comorbidities, long-term medication use, and dietary deficiencies, but it is still not known how often they occur in this group of patients. This study aimed to assess the prevalence of these disturbances in a group of hospitalized patients over 65 years of age according to age and sex. The study was conducted between January 2018 and September 2020 at the Central Clinical Hospital in Warsaw. A total of 66,450 calcium, magnesium, phosphate, and vitamin D concentration results were included in the analysis. Dysmagnesemia was present in 33% of the calcium results, dyscalcemia, dysphosphatemia, and dysvitaminosis D—in 23.5%, 26%, and 70% of the results, respectively. The magnesium concentration was found to be age-dependent, and older people were found to be at higher risk of developing abnormal magnesium concentrations (p < 0.001). Sex influenced the occurrence of abnormal magnesium (p < 0.001), vitamin D (p < 0.001), and calcium (p < 0.00001) concentrations, with hypercalcemia and hypervitaminosis D disorders being significantly more common in women (p < 0.0001). In conclusion, disorders of the calcium–magnesium–phosphate metabolism are common in hospitalized patients over 65 years of age, and the concentrations of these substances should be routinely monitored in this group

The Role of Light Kappa and Lambda Chains in Heart Function Assessment in Patients with AL Amyloidosis

There are reports indicating that myocardial dysfunction in systemic immunoglobulin light chain amyloidosis (AL amyloidosis) stems not only from the amyloid deposit in the organ but also the cardiotoxicity of the amyloid precursor free light chains (FLCs) circulating in the blood. The aim of the study is to analyze the role of sFLC κ and λ in the assessment of heart involvement and the degree of myocardial damage in AL amyloidosis. The study involved 71 patients diagnosed with primary AL amyloidosis. The relationship between sFLC concentrations and cardiac biochemical and echocardiographic parameters was assessed. The median concentrations of N-terminal pro b-type natriuretic peptide(NT-proBNP) and troponin I (TnI) were significantly higher in patients with amyloids formed from monoclonal λ chains compared to patients with monoclonal κ proliferation. In patients with heart involvement by amyloids formed from monoclonal FLC, the study demonstrated a statistically significant positive correlation between the concentration of monoclonal antibody λ chain and TnI (R = 0.688; p < 0.05), NT-proBNP (R = 0.449; p < 0.05), and the value of diastolic dimension of the interventricular septum (IVS; R = 0.496, p < 0.05). The above data indicate that the presence of monoclonal λ chains in patients with AL amyloidosis may be associated with more severe damage to cardiomyocytes and dysfunction of the myocardium

Increased Temperature Facilitates Adeno-Associated Virus Vector Transduction of Colorectal Cancer Cell Lines in a Manner Dependent on Heat Shock Protein Signature

Colorectal cancer (CRC) is one of the most common cancers in human population. A great achievement in the treatment of CRC was the introduction of targeted biological drugs and solutions of chemotherapy, combined with hyperthermia. Cytoreductive surgery and HIPEC (hyperthermic intraperitoneal chemotherapy) extends the patients’ survival with CRC. Recently, gene therapy approaches are also postulated. The studies indicate the possibility of enhancing the gene transfer to cells by recombinant adeno-associated vectors (rAAV) at hyperthermia. The rAAV vectors arouse a lot of attention in the field of cancer treatment due to many advantages. In this study, the effect of elevated temperature on the transduction efficiency of rAAV vectors on CRC cells with different origin and gene profile was examined. The effect of heat shock on the penetration of rAAV vectors into CRC cells in relation with the expression of HSP and AAV receptor genes was tested. It was found that the examined cells under hyperthermia (43°C, 1 h) are transduced at a higher level than in normal conditions (37°C). The results also indicate that studied RKO, HT-29, and LS411N cell lines express HSP genes at different levels under both 37°C and 43°C. Moreover, the results showed that the expression of AAV receptors increases in response to elevated temperature. The study suggests that increased rAAV transfer to CRC can be achieved under elevated temperature conditions. The obtained results provide information relevant to the design of new solutions in CRC therapy based on the combination of hyperthermia, chemotherapy, and gene therapy

Azithromycin and Chloramphenicol Diminish Neutrophil Extracellular Traps (NETs) Release

Neutrophils are one of the first cells to arrive at the site of infection, where they apply several strategies to kill pathogens: degranulation, respiratory burst, phagocytosis, and release of neutrophil extracellular traps (NETs). Antibiotics have an immunomodulating effect, and they can influence the properties of numerous immune cells, including neutrophils. The aim of this study was to investigate the effects of azithromycin and chloramphenicol on degranulation, apoptosis, respiratory burst, and the release of NETs by neutrophils. Neutrophils were isolated from healthy donors by density-gradient centrifugation method and incubated for 1 h with the studied antibiotics at different concentrations (0.5, 10 and 50 μg/mL—azithromycin and 10 and 50 μg/mL—chloramphenicol). Next, NET release was induced by a 3 h incubation with 100 nM phorbol 12-myristate 13-acetate (PMA). Amount of extracellular DNA was quantified by fluorometry, and NETs were visualized by immunofluorescent microscopy. Degranulation, apoptosis and respiratory burst were assessed by flow cytometry. We found that pretreatment of neutrophils with azithromycin and chloramphenicol decreases the release of NETs. Moreover, azithromycin showed a concentration-dependent effect on respiratory burst in neutrophils. Chloramphenicol did not affect degranulation, apoptosis nor respiratory burst. It can be concluded that antibiotics modulate the ability of neutrophils to release NETs influencing human innate immunity