Venom Immunotherapy Does Not Affect Survival of Patients with Malignant Tumor in Poland.

Background: Allergen immunotherapy (AIT) is a well-established and efficient method of causative treatment for allergic rhinitis, asthma and insect venom allergy. Traditionally, a recent history of malignant neoplasm is regarded as a contraindication to AIT due to concerns that AIT might stimulate tumor growth. However, there are no data confirming that the silencing of the Th2 response affects prognosis in cancer. Objectives: The aim of this study was to investigate frequency of malignant tumors in patients undergoing AIT and the association between AIT and cancer-related mortality. Patients and Methods: A group of 2577 patients with insect venom allergy undergoing AIT in 10 Polish allergology centers was screened in the Polish National Cancer Registry. Data on cancer type, diagnosis time and patients' survival were collected and compared with the general population. Results: In the study group, 86 cases of malignancies were found in 85 patients (3.3% of the group). The most common were breast (19 cases), lung (9 cases), skin (8 cases), colon and prostate cancers (5 cases each). There were 21 cases diagnosed before AIT, 38 during and 27 after completing AIT. Laplace's crude incidence rate was 159.5/100,000/year (general population rate: 260/100,000/year). During follow-up, 13 deaths related to cancer were revealed (15% of patients with cancer). Laplace's cancer mortality rate was 37.3/100,000/year (general population rate: 136.8/100,000/year). Conclusions: Malignancy was found in patients undergoing immunotherapy less often than in the general population. Patients with cancer diagnosed during or after AIT did not show a lower survival rate, which suggests that AIT does not affect the prognosis.

Mast Cells and Basophils in IgE-Independent Anaphylaxis.

Anaphylaxis is a life-threatening or even fatal systemic hypersensitivity reaction. The incidence of anaphylaxis has risen at an alarming rate in the past decades in the majority of countries. Generally, the most common causes of severe or fatal anaphylaxis are medication, foods and Hymenoptera venoms. Anaphylactic reactions are characterized by the activation of mast cells and basophils and the release of mediators. These cells express a variety of receptors that enable them to respond to a wide range of stimulants. Most studies of anaphylaxis focus on IgE-dependent reactions. The mast cell has long been regarded as the main effector cell involved in IgE-mediated anaphylaxis. This paper reviews IgE-independent anaphylaxis, with special emphasis on mast cells, basophils, anaphylactic mediators, risk factors, triggers, and management.

Platelet-activating factor as an endogenous cofactor of food anaphylaxis.

Anaphylaxis is a severe, acute, life-threatening generalized or systemic hypersensitivity reaction. The incidence of anaphylaxis is increasing worldwide, with medications and food contributing to most cases. Physical exercise, acute infections, drugs, alcohol, and menstruation are the external cofactors associated with more severe systemic reaction. The aim of this review is to show that platelet-activating factor contributes to the development of severe anaphylactic reaction, and even to anaphylactic shock.

The Dynamics of Changes in the Concentration of IgG against the S1 Subunit in Polish Healthcare Workers in the Period from 1 to 12 Months after Injection, Including Four COVID-19 Vaccines.

BACKGROUND: The presented research made it possible to obtain the characteristics of changes in anti-SARS-CoV-2 IgG within one year of vaccination in healthcare workers. MATERIALS AND METHODS: The research group consisted of 18,610 participants represented by medical and administration staff. IgG antibody concentrations were determined by ELISA. RESULTS: At 5-8 months after full vaccination, the levels of anti-SARS-CoV-2 IgG with equal vaccines were similar. The exception was JNJ-78436735, for which IgG levels were significantly lower. In the 9th month after vaccination, an increase in the anti-SARS-CoV-2 IgG level, suggesting asymptomatic infection, was observed in a large group of participants. Significantly higher levels of anti-SARS-CoV-2 IgG antibodies were observed after the booster dose compared to the second dose. The increase in antibodies was observed already around the 5th day after the injection of the booster dose, and was maximized at approximately the 14th day. CONCLUSION: The cut-off date for protection against the disease seems to be the period 8-9 months from the vaccination for mRNA vaccines and 5-6 months for vector vaccines. The introduction of a booster dose was the right decision, which could have a real impact on restricting the further transmission of the virus.

Anti-SARS-CoV-2 IgG against the S Protein: A Comparison of BNT162b2, mRNA-1273, ChAdOx1 nCoV-2019 and Ad26.COV2.S Vaccines.

BACKGROUND: COVID-19 vaccines induce a differentiated humoral and cellular response, and one of the comparable parameters of the vaccine response is the determination of IgG antibodies. MATERIALS AND METHODS: Concentrations of IgG anti-SARS-CoV-2 antibodies were analyzed at three time points (at the beginning of May, at the end of June and at the end of September). Serum samples were obtained from 954 employees of the Nicolaus Copernicus University in Torun (a total of three samples each were obtained from 511 vaccinated participants). IgG antibody concentrations were determined by enzyme immunoassay. The statistical analysis included comparisons between vaccines, between convalescents and COVID-19 non-patients, between individual measurements and included the gender, age and blood groups of participants. RESULTS: There were significant differences in antibody levels between mRNA and vector vaccines. People vaccinated with mRNA-1273 achieved the highest levels of antibodies, regardless of the time since full vaccination. People vaccinated with ChAdOx1 nCoV-2019 produced several times lower antibody levels compared to the mRNA vaccines, while the antibody levels were more stable. In the case of each of the vaccines, the factor having the strongest impact on the level and stability of the IgG antibody titers was previous SARS-CoV-2 infection. There were no significant correlations with age, gender and blood type. SUMMARY: mRNA vaccines induce a stronger humoral response of the immune system with the fastest loss of antibodies over time.

Tree nut allergy.

From a botanical point of view, a nut is a kind of dry, closed, unbroken, single-seeded fruit, which has a ligneous pericarp made up of several fruiting bodies surrounded by one free semen. The term "allergy to tree nuts" includes allergies to almonds, Brazil nuts, cashew nuts, hazelnuts, chestnuts, macadamia nuts, pecan nuts, pistachios and walnuts. All tree nuts belong to five orders of plants: Rosaceae, Fagales, Sapindales, Ericales and Proteales. Allergies to tree nuts usually start in childhood, but unlike other food allergies, they rarely fade away and generally persist throughout life. They are one of the main causes of serious allergic reactions ending in death in both children and adults. The epidemiology of allergy to nuts is variable and depends mainly on the geographical zone and eating habits. In northern Europe, hazelnut allergy is prevalent, whereas in the USA the most common is allergy to peanuts and, when taking tree nuts into consideration, to walnuts. The diagnosis of allergies to nuts is difficult and requires the use of the most modern research tools including molecular diagnostic techniques.

Differences in the Concentration of Anti-SARS-CoV-2 IgG Antibodies Post-COVID-19 Recovery or Post-Vaccination.

At the end of 2020, population-based vaccination programs with new generation mRNA-based vaccines began almost all over the world. The aim of the study was to evaluate the titer of anti-SARS-CoV-2 IgG antibodies against the S1 subunit of the virus's spike protein as a marker of the humoral response in 477 patients and the concentration of interferon-gamma as an indicator of cellular response in 28 individuals. In our studies, we used serological enzyme-linked immunosorbent assays. IgG was measured in weeks 2 and 3 after the first dose and 1-5 weeks after the second dose of an mRNA vaccine in seropositive and seronegative individuals as well as in symptomatic and asymptomatic convalescents. High levels of antibodies were observed in 98% of our vaccinated cohort, and the presence of protective T cells was confirmed in the blood samples of all participants. The humoral immune response is diversified and is visible as early as 2-3 weeks after the first dose of the mRNA vaccine. The level of protection increased significantly after the second dose, with the increase being much greater in pre-vaccine healthy subjects and less in convalescents. In the second and third weeks after the second dose, the concentration of IgG antibodies was the highest, and in the following weeks, it decreased gradually. Regular serological measurements on eight subjects show that antibody titers are lower four months after vaccination than before the second dose.

The effect of hymenoptera venom immunotherapy on neutrophils, interleukin 8 (IL-8) and interleukin 17 (IL-17).

OBJECTIVES: Venom immunotherapy (VIT) is an effective treatment method and is addressed to patients with a history of an anaphylactic reaction to Hymenoptera stings. However, the immunological mechanisms of protection have not been explained yet. The objective of this study was to analyze neutrophils, interleukin 8 (IL-8) and interleukin 17 (IL-17) before and after the initial phase of the immunotherapy. MATERIAL AND METHODS: Overall, 40 individuals, including 20 wasp venom sensitized and 20 bee venom sensitized patients, were included in the study. The patients had had a history of severe allergic reactions type III and IV according to Mueller's classification. An ultra-rush VIT protocol was used in this study. The concentration of serum IL-8 and IL-17A was determined using the ELISA enzymatic method. RESULTS: The authors demonstrated a significant rise in the IL-8 level after the immunotherapy, compared to baseline (14.9 vs. 24.7, p < 0.05). The rise in the neutrophils level was also noticeable but proved to be barely out of the range of statistical significance (4.3 vs. 5.0, p = 0.06). The shift in IL-17A was negligent and not statistically significant in the paired samples t-test (1.6 vs. 1.5, p = 0.34). CONCLUSIONS: Venom immunotherapy induces neutrophils and IL-8 activity after 2 days. After the desensitization, the level of IL-17A did not change. Int J Occup Med Environ Health. 2020;33(6):811-7.

Expression of eosinophils, RANTES and IL-25 in the first phase of Hymenoptera venom immunotherapy.

INTRODUCTION: Venom immunotherapy (VIT) can protect against severe anaphylactic reactions (SR) in 80-100% of subjects allergic to Hymenoptera venom. The mechanisms of induction of immunological tolerance produced by VIT are still little known. It has been shown that VIT modulates Treg activity, Th2 or Th1 cells or both, increases production of IL-10, decreases secretion of IL-13, and causes an IgG4/IgE ratio shift. AIM: To investigate the blood eosinophil count, CCL5/RANTES and IL-17E/IL-25 concentrations before and after the initial phases of the rush protocol of VIT. MATERIAL AND METHODS: Forty individuals (14 males, 26 females) of mean age 41.03 ±12.43 years were included in the study. The peripheral eosinophils and the concentration of serum interleukin IL-17E/IL-25 and RANTES were determined before and after the initial phase of VIT. RESULTS: Paired sample t-test revealed that all patients after VIT had significantly higher eosinophil levels compared to the baseline (mean: 0.42 vs. 0.64, p < 0.05). Moreover, in subjects treated with bee venom, RANTES levels proved to rise significantly (51 × 103 vs. 62 × 103, p < 0.05) while IL-17E/IL-25 dropped with near-marginal significance (916 vs. 650, p = 0.069). CONCLUSIONS: Our immunological study on the early phase of venom immunotherapy suggested that eosinophils, cytokines such as CCL5/RANTES and IL-17E/IL-25 contribute to the immunological response.

Fear of stinging insects in relation to state anxiety and trait anxiety in a group of patients with hymenoptera venom allergy undergoing immunotherapy.

INTRODUCTION: The level of fear of hymenoptera associated with stinging or envenomation may depend on situational factors and on trait anxiety characteristic of each patient. AIM: To assess the relationship between fear of stinging insects on the one hand and state anxiety and trait anxiety on the other in a group of patients with hymenoptera venom allergy. MATERIAL AND METHODS: The study was conducted by the Department of Allergy, Clinical Immunology and Internal Diseases, Dr J. Biziel University Hospital No. 2 in Bydgoszcz, Poland. A total of 114 patients (71 women (63%) and 43 men (37%)) with hymenoptera venom allergy undergoing immunotherapy participated in the study. The State-Trait Anxiety Inventory (STAI) and a dedicated scale developed by the authors for this study were used. RESULTS: State anxiety was found to significantly (p < 0.05) correlate with anxiety in the present moment (R = 0.247), in a situation of real danger (appearance of an insect) (R = 0.223) and during the spring and summer seasons (R = 0.278). Trait anxiety was found to significantly (p < 0.05) correlate with anxiety before immunotherapy (R = 0.261), in the present moment (R = 0.257), in a situation of real danger (appearance of an insect) (R = 0.254), and after an insect sting (R = 0.236). These were also weak correlations. The correlation between trait anxiety and anxiety during the spring and summer seasons was moderate (R = 0.331). CONCLUSIONS: The levels of trait and state anxiety are associated with the magnitude of the fear of the danger. Respondents showed a higher level of anxiety in a situation of danger and after an insect sting.

Omalizumab improves forced expiratory volume in 1 second in patients with severe asthma.

INTRODUCTION: Asthma is a multiphenotypic disease, and therapeutic managenment in patients with severe asthma is particulary difficult, with conventional treatment of severe asthma showing poor efficacy. AIM: To analyse forced expiratory volume in 1 s (FEV1) following the adminstration of omalizumab. MATERIAL AND METHODS: Six patinents (mean age: 50 ±12.6) with severe, uncontrolled asthma according to the GINA guidelines were enrolled in the study. RESULTS: Treatment with omalizumab increased in all subjects FEV1 by 17.28 ±13.4% after months and 18.57 ±13.4% after 12 months of treatment. CONCLUSIONS: These results provides further evidence that therapy with omalizumab improves spiromtric parameters in severe asthma.

Venom immunotherapy and pregnancy.

INTRODUCTIONS: The efficiency of venom immunotherapy (VIT) has been well documented by many studies. However, the most important for VIT is safety, particularly for a pregnant woman and a fetus. AIM: To establish the influence of continuation of VIT on pregnant women and offspring. MATERIAL AND METHODS: The 6 women became pregnant during a specific immunotherapy. We retrospectively analyzed the influence of the immunotherapy on any complications for the pregnant women and their infants. RESULTS: Of the 6 patients who participated in this study, four had hyperemesis gravidarum, nausea, and heartburn, and two of them had gestational diabetes mellitus symptoms, typical of pregnancy. The observation indicated that VIT was safe for the pregnant women and their offspring. CONCLUSIONS: The VIT is an appropriate therapeutic method for most patients with severe anaphylactic reactions after a hymenoptera sting. The observation indicated that VIT is safe for pregnant women and for their infants.

ABO blood groups, Rhesus factor, and anaphylactic reactions due to Hymenoptera stings.

INTRODUCTION: Numerous publications indicate that the prevalence of some infectious, neoplastic and immunological diseases are associated with ABO blood groups. OBJECTIVE: The aim of this study was to verify whether ABO and Rh blood groups are associated with severe anaphylactic reactions after Hymenoptera stings. MATERIAL AND METHODS: A study was undertaken of 71,441 Caucasian subjects living in the same geographic area. The study group included 353 patients with diagnosed systemic anaphylaxis to Hymenoptera venom. Control group included 71,088 healthy blood donors. Frequencies of ABO and Rhesus groups in the study and control groups were compared using univariate and multivariate analyses. RESULTS: No statistically significant interactions were observed between the ABO blood group and anaphylactic reactions to Hymenoptera.

Expression of IL-17A concentration and effector functions of peripheral blood neutrophils in food allergy hypersensitivity patients.

Lymphocytes Th17 and other types of immune system cells produce IL17. By induction of cytokines and chemokines, the IL17 cytokine is involved in mechanisms of allergic reaction with participation of neutrophil granulocytes. It affects activation, recruitment, and migration of neutrophils to the tissues, regulating inflammatory reaction intensity. Excited neutrophils secrete inter alia elastase and reactive oxygen species (ROS)--significant mediators of inflammation process responsible for tissues damage.The aim of the study was to evaluate the concentrations of serum interleukin 17A, serum neutrophil elastase, and ROS production by neutrophils in patients with food allergy.The study included 30 patients with food allergy diagnosed based on interview, clinical symptoms, positive SPT, placebo controlled double-blind oral provocation trial, and the presence of asIgE in blood serum against selected food allergens using fluoro-immuno-enzymatic method FEIA UNICap 100. The control group consisted of 10 healthy volunteers. The concentrations of IL17A were determined in all patients using ELISA method with eBioscience kits, and elastase using BenderMed Systems kits. Chemiluminescence of non-stimulated neutrophils was evaluated using luminol-dependent kinetic method for 40 min on Luminoskan (Labsystems luminometer).The results of serum IL-17A concentrations and the values of chemiluminescence obtained by non-activated neutrophils, as well as elastase concentrations, were higher in patients with food allergic hypersensitivity compared to healthy volunteers.This study demonstrates a significance of IL-17A and activated neutrophil granulocytes in the course of diseases with food allergic hypersensitivity.

Platelet activating factor in allergies.

The platelet-activating factor (PAF) produced and released by mast cells, basophils, neutrophils, eosinophils, fibroblasts, platelets, endothelial cells, and even cardiac muscle cells plays an important role in inflammatory and thrombotic diseases. PAF has been shown to be an important mediator in anaphylaxis. Serum level of the factor correlates with the severity of systemic reactions. PAF is also involved in asthamatic patients' bronchoconstriction, mucus hypersecretion, and inflammation of bronchi. Furthermore, increased plasma levels of PAF have been reported in patients with urticarial. Studies have shown that PAF increases the permeability of skin's capillaries and indices the development of wheals, flare, and inflammatory reactions in the skin.This review focuses on the actions of the PAF on the eosinophiles and mast cells. Following that pathophysiological mechanism of the PAF in anaphylaxis bronchial asthma and urticaria was discussed.

Anaphylaxis as a cause of hospitalization--a single academic centre experience.

INTRODUCTION: In recent years, more and more often the increase in incidence of allergies is observed. According to the WHO, they are getting the fourth position amongst the most frequent diseases after cancers, cardiovascular diseases and AIDS. Anaphylaxis is a severe, life-threatening, systemic or generalised immediate hypersensitivity reaction. The analysis of the causes and the clinical picture of anaphylaxis in patients treated at single academic hospital centre was the purpose of the study. MATERIAL AND METHODS: The study was based on retrospective analysis of case records of the patients hospitalised at the Chair and Department of Allergology, Clinical Immunology and Internal Diseases, the Jan Biziel University Hospital in Bydgoszcz in the years 2005-2010. 132 patients, in whom anaphylactic reaction appeared, were analysed. The examined population included 70 men and 62 women at 16-95 years of age. RESULTS: The conducted examinations allowed to obtain information about the causes and the course of anaphylactic reactions. The problem of hypersensitivity to substances of various origin (biological or synthetic) can concern everyone irrespective of sex and age. Nevertheless, the phenomenon of anaphylaxis more often occurred in the examined men than women. Most cases of anaphylactic reactions were reported in the 26-50 age range. Based on the presented results, no regularity was observed in anaphylaxis clinical picture and its causative factor. CONCLUSIONS: It is difficult to forecast the course of the reaction based on the causative factor, for anaphylactic reaction is characterised by a great individual changeability and intensity of the first symptoms.

Angiogenesis in bronchial asthma.

Bronchial asthma is a chronic inflammatory disease characterised by airflow obstruction that may be reversed spontaneously or in response to treatment. The airway inflammation can lead to structural changes and remodelling consisting of subepithelial layer thickening, airway smooth muscle hyperplasia and angiogenesis. Subepithelial hypervascularity and angiogenesis in the airways are part of the structural airway wall in asthma. Increased vascularity of bronchial mucosa is closely related to the expression of angiogenic factors like vascular endothelial growth factor (VEGF), angiopoietin and hypoxia-inducible factor (HIF). The scope of the present review is to summarise the roles of anagiogenic factors and treatment in vascular development.

[Antimicrobial peptides in asthma pathogenesis]. / Udzial peptydów antydrobnoustrojowych w patogenezie astmy oskrzelowej

Antimicrobial peptides exhibit activity against bacteria, viruses, fungi, and parasites. They have been described not only as endogenous antibiotics but also as immune modulators with an impact on innate and adaptive immune functions. Asthma is one of the most common diseases, characterized by chronic airway inflammation, bronchial hyperreactivity and asthma attacks. Airway inflammation in asthma is characterized by allergic phenotypes, such as dense infiltration of eosinophils, mast cells, Th 2 lymphocytes and monocytes. Viral infections are often the cause of asthma exacerbation. This review highlights recent observations on the role of antimicrobial peptides in asthma pathogenesis.

[Gene and environmental interactions of food allergy]. / Czynniki genetyczne i srodowiskowe w rozwoju alergii na pokarmy.

Food allergy is now looming as a major health issue with significant implications. In westernized countries, recent reports show a rise in allergic diseases, in particular food allergy. It affects approximately 5-8% of children and 1-5% of adults. Despite this, our current understanding of the immunological and biological mechanisms of food allergy is still incomplete. It is generally believed that food allergy is determined by both genetic and environmental factors. There is some evidence that epigenetic modifications may affect the prevalence of food allergies. This paper discusses the current state of knowledge regarding genetic, epigenetic and environmental factors of food allergy.