Contribution of Kazal-Like Domains of the Serine Protease Inhibitor-1 from Toxoplasma gondii in Asthma Therapeutic Vaccination Effectiveness

<b><i>Background:</i></b> We have previously showed rTgPI-1 tolerogenic adjuvant properties in asthma treatment, turning it a promising candidate for allergen-specific immunotherapy. This therapy is an alternative treatment to control asthma that still presents several concerns related to its formulation. rTgPI-1 contains independent inhibitory domains able to inhibit trypsin and neutrophil elastase, both involved in asthma pathology. <b><i>Objectives:</i></b> In view of the need to design rational therapies, herein we investigated the contribution of the different inhibitory domains in rTgPI-1 therapeutic effectiveness. <b><i>Methods:</i></b> BALB/c mice were rendered allergic by intraperitoneal OVA-alum sensitization and airway challenged. Once the asthmatic phenotype was achieved, mice were intranasally treated with OVA combined with the full-length recombinant protein rTgPI-1 or its truncated versions, Nt (containing trypsin-inhibitory domains) or Ct (containing neutrophil elastase-inhibitory domains). Afterward, mice were aerosol re-challenged. <b><i>Results:</i></b> Asthmatic mice treated with the neutrophil elastase- or the trypsin-inhibitory domains separately failed to improve allergic lung inflammation. Only when all inhibitory domains were simultaneously administered, an improvement was achieved. Still, a better outcome was obtained when mice were treated with the full-length rTgPI-1. <b><i>Conclusions:</i></b> Adjuvant ability depends on the presence of all its inhibitory domains in a single entity, so it should be included in potential asthma treatment formulations as a full-length protein.

Role of periostin in evaluating the responsiveness of allergic patients to allergen-specific immunotherapy

Objectives: Allergen-specific immunotherapy (AIT) has been considered the most effective treatment for IgE mediated allergies, especially respiratory allergies. Several biomarkers have been developed to evaluate the clinical efficacy of AIT, yet none of them have been thoroughly validated. So our objective here is to investigate the usefulness of periostin as a biomaker for monitoring the efficacy of allergen immunotherapy. Materials and methods: This study included 46 healthy non-atopic volunteers and 46 patients with allergic rhinitis (AR). They were sensitized only to date palm pollen. The participants were tested by skin prick test and total serum IgE levels were measured. Serum samples were collected from healthy subjects and allergic patients before and after the one-year AIT. Serum levels of periostin, eotaxin, and sIL-2R were estimated by ELISA. Symptom scores in the allergic patients were also evaluated before and after completing one year AIT. Results: There is a significant increase in serum levels of IgE, periostin, sIL-2R, and eotaxin in allergic patients as compared to healthy controls. Symptom scores, sIL-2R and serum periostin levels were significantly decreased after one-year AIT in AR patients. Conclusion: Periostin can be used as a biomarker to evaluate AIT efficacy in AR patients. Bangladesh Journal of Medical Science Vol. 21(1) 2022 Page : 184-190

Preparation and Characterization of a Glycyrrhizic Acid-Based Drug Delivery System for Allergen-Specific Immunotherapy

The most effective method of treating allergic diseases, aimed not at relieving symptoms, but at eliminating the cause of the disease, is allergen-specific immunotherapy (AIT). To reduce the risk of side effects and improve the delivery of allergens to the mucosa, various delivery systems, such as liposomes, dendrimers, nanoparticles, etc., can be used. To date, there are data on the creation of delivery systems based on glycyrrhizic acid (GA) and its derivatives, but such a delivery system has not been used for allergen-specific therapy until now. It is also known that GA has an anti-inflammatory effect, shifts the balance towards Th1, and increases the number of Treg cells, meaning that it could potentially enhance the anti-allergic effect of AIT and reduce the risk of unwanted side effects. Thus, the study of the immunomodulatory effect of the supramolecular complexes (micelles) of GA with extracts of allergens holds promise for the development of new drugs for AIT.

Specific immunotherapy in the complex treatment of ovarian cancer

The article is devoted to the search for new solutions in the field of treatment of malignant ovarian tumors and, in particular, new approaches for overcoming immune resistance in a complex method of therapy. The experience of treating this pathology with an original method of postoperative immunotherapy using autologous immunomodulators, which, due to its simplicity and relatively low cost, should be widely used in gynecological oncology, is considered.

Honey Bee Venom Re-Challenge During Specific Immunotherapy: Prolonged Cardio-Pulmonary Resuscitation Allowed Survival in a Case of Near Fatal Anaphylaxis

BACKGROUND Specific immunotherapy for patients with honey bee hypersensitivity is commonly applied. Re-challenge with venom is performed to prove protection.CASE PRESENATION We report a case of near fatal anaphylaxis with asystolia for 24 minutes in a 35-years-old patient with mastocytosis after honey bee sting challenge despite 5-years of specific immunotherapy. Successful cardio-pulmonary resuscitation (CPR) was applied for 32 minutes.CONCLUSION This intervention demonstrates, that in anaphylaxis with cardio-vascular arrest prolonged CPR for up to 40 minutes might be appropriate to overcome half time span of massively released histamine. Failure of specific immunotherapy was possibly due to sensitization to the allergen Api m10, probably underrepresented in commercial honey bee venom extracts. Also, molecular analyses might alert to potential unsuccessful outcome of venom specific immunotherapy especially in high-risk patients such as mastocytosis.

Standardized Quantitative Evaluation of Clinical Effectiveness and Side Effect Profile of Subcutaneous and Sublingual Allergen-Specific Immunotherapy in Children: A 5-Year Single Center Experience

Objective: Allergen-specific immunotherapy (allergen-SIT) is a treatment method with variable efficacy in allergic diseases. This study aimed to investigate the effectiveness of allergen immunotherapy, frequency of LRs and SRs and variables affecting these parameters in patients who underwent allergen-SIT. Materials and Methods: In this study, the recorded data of 81 patients, who received subcutaneous (SCIT) or sublingual (SLIT) allergen immunotherapy for respiratory allergic diseases between 2014 and 2019, were analyzed. In asthma and/or allergic rhinoconjunctivitis (ARC) patients, the effectiveness of treatment was evaluated by analysing the change rates in disease symptom, medication and combined scores (symptom + medication) and visual analog score (VAS). Treatment success was defined by the degree of decrease in scores as; high response above 50%; low response between 20-50%; and failure <20%.Results: The mean age of allergen-SIT initiation was 11.4± 3.1 years. Diagnostic distributions of the patients were asthma (± ARC) in 64.2%, and ARC (without asthma) in 35.8%. The mode of allergen-SIT was SCIT in 77.8% (65% asthma and 35% ARC) and SLIT in 22.2% (61.1% asthma and 38.9% ARC). The main allergens used in allergen-SIT were mite (79%), grass-grain pollen (33.3%), alternaria (9.9%) and olea (8.6%). There was a significant decrease in symptoms, medication, combined and VAS scores in the asthma and ARC groups (p <0.0001), when end-SCIT values were compared to baseline. SLIT also resulted in significant decreases in these scores except asthma medication score. Among the asthma patients the rate of high-responders was 88.8% by SCIT and 50% by SLIT, according to combined asthma score. Among the ARC (without asthma) patients the rate of high-responders was 100% for both SCIT and SLIT. SCIT resulted in local (LR) and systemic side effects (SR) in 18% and 0.6% (all Grade I and Grade II) of the total injections performed. A high number of total injections was significantly associated with higher LR and SR rates. While LR was observed in 16.6% of the patients who underwent SLIT, no systemic reaction was found in any of the patients. Conclusion: SCIT was highly successful in the treatment of asthma and ARC in terms of the degree of therapeutic response. SLIT resulted in a high rate of good response in ARC patients, but a lower response degree in asthmatic patients. Systemic side effects were very low as a result of close risk monitoring and the dose adjustments performed. Keywords: Allergen-specific immunotherapy, SCIT, SLIT, efficacy, symptom score, medication score, visual analog score, side effects

Analysis of the dynamics of clinical indicators in patients with allergic rhinitis with sensitization to pollen and household allergens using combined allergen-specific immunotherapy

The aim of this study was to evaluate the clinical efficacy of combined allergen-specific immunotherapy (ASIT) in patients with allergic rhinitis (AR) with combined sensitization to pollen and household allergens. To achieve this goal, 49 patients with AR of working age were examined – 35.5±1.5 years with clinical manifestations of seasonal rhinoconjunctival syndrome with a long period of 9.2±1.1 years, among which there were 25 (51.0%) males and 24 (49%) females. All patients were divided into 2 homogeneous groups by age, sex, duration of the disease, the average number of etiologically significant allergens: the main one – 31 patients who received combined ASIT with solutions of pollen and household allergens and a comparison group – 18 patients for whom only pollen allergens were used. Allergological examination included anamnesis, skin tests with pollen allergens (wormwood, ragweed, quinoa, corn, etc.) and household (house dust, mites, epidermal agents) and / or molecular research methods using the ALEX technology. The quantitative integral assessment of the intensity of AR clinical symptoms was calculated as a total score for the main symptoms. The maximum score for the severity of nasal symptoms – 12, eye - 6, total – 18. The results obtained and their analysis indicate that under the influence of ASIT pollen and household allergens in patients there is a significant and reliable decrease in the intensity of clinical manifestations of seasonal rhinoconjunctive syndrome: nasal manifestations – by 52,2%, conjunctival – by 60%, integral – by 54.3% and an increase of 2.2 times in the percentage of patients in the main group with the disappearance or minimization of clinical symptoms of the disease after treatment compared with patients from the comparison group, which convincingly proves and confirms high efficiency of the selected type of therapy in patients with AR in combination with sensitization to pollen and household allergens.

Specific Immunotherapy in a Murine Model of Grass Pollen (Phl p5b)-Induced Airway Inflammation

Background: The use of ovalbumin as a model allergen in murine models of allergic asthma is controversially discussed since it is not an aeroallergen and sensitization can only be achieved by using strong Th2-inducing adjuvants. Therefore, in this study, a murine model of asthma has been established in which sensitization against the major grass pollen allergen Phl p5b was performed without using aluminum hydroxide (alum). We used this model for specific immunotherapy.Methods: Female, 5–6-week-old mice were sensitized by six subcutaneous (s.c.) injections of 20 μg Phl p5b followed by four provocations to induce allergic airway inflammation. For desensitization, 1 mg of Phl p5b was injected subcutaneously during allergen challenge for one to a maximum of four times. Three days after the last challenge, the allergic immune response was analyzed.Results: Sensitized and challenged animals showed a significant infiltration of eosinophils into the airways, and the production of interleukin-5 (IL-5) by in vitro re-stimulated splenocytes could be detected. Furthermore, hyper-responsiveness of the airways was verified by invasive measurement of airway resistance in methacholine-challenged animals. Desensitized animals showed a significant reduction of all parameters.Conclusion: In this study, a murine model of asthma has successfully been established by sensitization against the clinically relevant allergen Phl p5b without using alum. S.c. injection of allergen dose dependently led to desensitization of sensitized mice. We suggest that this model is useful to study adjuvant effects of immune modulatory substances on immunotherapy without the interference of alum.