IgE-mediated Allergic Diseases Research Articles

AIT: New Avenues in Allergen Immunotherapy.

During the last decades a substantial increase of allergic diseases has been noticed including allergic asthma and rhinoconjunctivitis as well as food allergies. Since efficient avoidance of airborne - and often hidden - food allergens is not possible, allergen immunotherapy (AIT) is the only causative treatment with the goal of inducing allergen tolerance in affected individuals. Efficacy as well as safety of AIT significantly depends on how the allergen is presented to the immune system, meaning both the route and the form of its application. Here, new ways of allergen administration have lately been explored, some of which are auspicious candidates for successful implementation in the therapeutic management of immediate-type allergies. While the first oral AIT has been approved recently by the FDA for the treatment of peanut allergy, further interesting routes of allergen application include either epicutaneous, intradermal, intranasal, or intralymphatic delivery. Besides, rather the immunologically relevant peptides instead of whole allergen may be administered to develop tolerance. In this chapter, we will describe these new and promising avenues of allergen application in the field of AIT. In addition, we will discuss their potential for future treatment of IgE-mediated allergic diseases enhancing therapeutic efficiency while further minimizing the risks of adverse events.

Anti-IgE: A treatment option in allergic rhinitis?

Background: Allergic rhinitis (AR) is the most common IgE-mediated allergic disease. Multiple clinical trials have demonstrated promising results on the AR treatment with biologics, in particular with the use of omalizumab – an anti-IgE antibody. Omalizumab has also been established in the routine management of allergic asthma and chronic idiopathic urticaria. However, currently there is no approved license for the use of biologics in AR in Germany. Materials and methods: A systematic literature review has been completed including randomized controlled trials, meta-analyses, and reviews on the treatment of AR with omalizumab. Results: The systematic review demonstrates strong evidence supporting the use of omalizumab in the treatment of AR with regard to symptom control, safety profile, and management of comorbidities. Conclusion: Omalizumab is a good and safe option in the treatment of AR in terms of symptom control and the management of pre-existing comorbidities. Further clinical trials with other biologics in the management of AR are needed and are expected to follow soon.

Molecular allergodiagnostics capabilities in determining the indications for allergen-specific immunotherapy with house dust mites allergen and its effectiveness in atopic dermatitis patients

BACKGROUND:Atopic dermatitis (AD) is a widespread chronic inflammatory skin disease, in the development of which complex genetic and immune mechanisms, environmental factors, allergens, are involved. An effective method of treating IgE-mediated allergic diseases is allergen-specific immunotherapy (ASIT), which affects all pathogenetically significant links of the allergic process. It is known that as a result of ASIT tissue sensitivity to an allergen, nonspecific tissue hyperreactivity and the intensity of allergic inflammation decrease, which testifies to the rearrangement of the cellular response from Th2 to Th1 with a corresponding change in the cytokine profile. Currently, dozens of scientific papers on the efficacy and safety of subcutaneous and sublingual ASIT in AD have been published; however, the question of the advisability of its appointment still remains unresolved.
 AIM:To investigate the ASIT with house dust mite (HDM) allergens efficacy in AD patients, considering the results of molecular allergy diagnosis.
 MATERIALS AND METHODS:The study was conducted as a prospective comparative open study, including 32 patients with AD (20 children and 12 adults), 90.6% were diagnosed with concomitant respiratory allergic diseases. Molecular allergodiagnostics was performed using microchip technology with purified natural or recombinant allergen components immobilized in the solid phase (Immuno-Solid phase Allergen Chip, ISAC) to quantify allergen-specific IgE (asIgE) against 112 allergen molecules from 51 allergen sources in one study (ImmunoCAP ISAC (Thermofisher, Phadia, Uppsala, Sweden). Patients were divided into two groups depending on the profile of molecular sensitization: with the presence or absence of asIgE to the major allergens ofD. farinaeand/orD. pteronyssinusDer p 1 (p 2) and/or Der f 1 (f 2). All patients passed three consecutive courses of subcutaneous ASIT with water-salted HDM allergens produced by I.I. Mechnikov Biomed (Russia) under an accelerated scheme for 3 years. To assess the severity of the disease, the SCORAD indices, the Investigators Global Assessment (IGA), and the dermatological quality of life index (DLQI) were used.
 RESULTS:Patients with sensitization to major allergens ofD. farinaeand/orD. pteronyssinusDer p 1 (f 1) and/or Der p 2 (f 2) more often achieved a significant improvement of AD symptoms according to the SCORAD index (OR 3.929, 95% CI: 0.879; 17.56), as well as they more often achieved IGA values of 1 or 0 after three courses of ASIT (OR 3.556, CI 95% 0.73017.324) and more often assessed the effectiveness of ASIT as excellent and good in comparison with patients without sensitization to these components. The median and interquartile range of the DLQI index before treatment in group 1 was 17 [14; 20] points, in group 2 14 [12; 18], after the 3rdcourse of ASIT: 6 [2; 10] and 8 [3; 10] points in groups 1 and 2, respectively. Adverse events were rare, their frequency did not significantly differ in both groups.
 CONCLUSION:ASIT with HDM allergens is an effective and safe method of treatment of AD patients. Determination of the molecular spectrum of sensitization to HDM allergens components allows to justify the indications and predict the effectiveness of ASIT.

Effect of heat, enzymatic hydrolysis and acid-alkali treatment on the allergenicity of silkworm pupa protein extract

Silkworm pupae are edible insects with high-quality nutrition in many Asian countries, but consumption of silkworm pupae can cause severe IgE-mediated allergic disease. The aim of this study was to investigate the effect of heat, enzymatic hydrolysis and acid-alkali treatment on the allergenicity of silkworm pupa protein extract (SPPE). Heating reduced the allergenicity of SPPE when the temperature was higher than 60 °C. Spectroscopy studies suggested an unfolded conformation of SPPE with heating, dependent on temperature and time. Enzymatic hydrolysis revealed that SPPE at 25 to 33 kDa contained pepsin- and trypsin-resistant allergens. The results of acid-alkali treatment suggested that low pH can promote hydrolysis of SPPE and decrease its allergenicity. Thus, heat, enzymatic hydrolysis and acid-alkali treatment can significantly decrease the allergenicity of SPPE, with heat-, enzyme- and acid-alkali–resistant allergens at 25 to 33 kDa SPPE. This study can help in the development of methods to prepare silkworm pupa protein.

IgE Epitope Profiling for Allergy Diagnosis and Therapy - Parallel Analysis of a Multitude of Potential Linear Epitopes Using a High Throughput Screening Platform.

Immunoglobulin E (IgE) is pivotal for manifestation and persistence of most immediate-type allergies and some asthma phenotypes. Consequently, IgE represents a crucial target for both, diagnostic purposes as well as therapeutic approaches. In fact, allergen-specific immunotherapy – aiming to re-route an IgE-based inflammatory response into an innocuous immune reaction against the allergen – is the only curative approach for IgE-mediated allergic diseases known so far. However, this requires the cognate allergen to be known. Unfortunately, even in well-characterized allergics or asthmatics, often just a small fraction of total IgE can be assigned to specific target allergens. To overcome this knowledge gap, we have devised an analytical platform for unbiased IgE target epitope detection. The system relies on chemically produced random peptide libraries immobilized on polystyrene beads (“one-bead-one-compound (OBOC) libraries”) capable to present millions of different peptide motifs simultaneously to immunoglobulins from biological samples. Beads binding IgE are highlighted with a fluorophore-labeled anti-IgE antibody allowing fluorescence-based detection and isolation of positives, which then can be characterized by peptide sequencing. Setting-up this platform required an elaborate optimization process including proper choice of background suppressants, secondary antibody and fluorophore label as well as incubation conditions. For optimal performance our procedure involves a sophisticated pre-adsorption step to eliminate beads that react nonspecifically with anti-IgE secondary antibodies. This step turned out to be important for minimizing detection of “false positive” motifs that otherwise would erroneously be classified as IgE epitopes. In validation studies we were able to retrieve artificial test-peptide beads spiked into our library by using IgE directed against those test-peptides at physiological concentrations (≤20 IU/ml of specific IgE), and disease-relevant bead-bound epitopes of the major peanut allergen Ara h 2 by screening with sera from peanut allergics. Thus, we established a platform with which one can find and validate new immunoglobulin targets using patient material which displays a largely unknown immunoglobulin repertoire.

IgE Autoreactivity in Atopic Dermatitis: Paving the Road for Autoimmune Diseases?

Atopic dermatitis (AD) is a common skin disease affecting 20% of the population beginning usually before one year of age. It is associated with the emergence of allergen-specific IgE, but also with autoreactive IgE, whose function remain elusive. This review discusses current knowledge relevant to the mechanisms, which leads to the secretion of autoreactive IgE and to the potential function of these antibodies in AD. Multiple autoantigens have been described to elicit an IgE-dependent response in this context. This IgE autoimmunity starts in infancy and is associated with disease severity. Furthermore, the overall prevalence of autoreactive IgE to multiple auto-antigens is high in AD patients. IgE-antigen complexes can promote a facilitated antigen presentation, a skewing of the adaptive response toward type 2 immunity, and a chronic skin barrier dysfunction and inflammation in patients or AD models. In AD, skin barrier defects and the atopic immune environment facilitate allergen sensitization and the development of other IgE-mediated allergic diseases in a process called the atopic march. AD is also associated epidemiologically with several autoimmune diseases showing autoreactive IgE secretion. Thus, a potential outcome of IgE autoreactivity in AD could be the development of further autoimmune diseases.

Pattern of skin sensitivity to various aeroallergens by skin prick test in patients of allergic airway disease in South Western Maharashtra

BackgroundThe prevalence of allergic diseases such as asthma and allergic rhinitis is high in the general population, and aeroallergens are the most common allergens that cause airway inflammation. Skin prick testing (SPT) is a validated method to diagnose IgE-mediated allergic diseases. The knowledge of allergen sensitivity pattern in this part of India is limited. The present study was undertaken to identify common aeroallergens prevalent in this area using a standardized SPT. MethodsWe did a cross-sectional hospital-based study. A total of 330 patients of proven allergic airway disease underwent SPT. We used a validated skin prick test which included 22 allergen extracts, 1 positive control, and 1 negative control. ResultsA total of 327 patients were included in the study. Two hundred seventy-one (82.27%, n = 327) patients had a positive SPT to one or more aeroallergen extract. The sensitivity of Dermatophagoides pteronyssinus (49.85%) was seen in the maximum number of people followed by Dermatophagoides farinae (47.70%). ConclusionsIn our study, dust mites were the most common aeroallergen seen in maximum study subjects.

Fine-tuning the use of a skin prick test device

BackgroundSkin prick tests (SPTs) are the gold standard for the diagnosis of IgE-mediated allergic diseases. Newly introduced devices have different results in performance. This study aimed to provide data for sensitivity, reproducibility, and acceptability of a new SPT device by using different techniques. MethodsThe study was conducted in 4 sections. Different application techniques were evaluated. In the first section, a drop of histamine/saline was put by vial (V). In the second section, it was taken from a well via the test device (W). ALK® Lancet served as a reference in both sections. The techniques were as follows; 1) apply vertical pressure (VP/WP), 2) apply vertical pressure and rotate 90° clockwise (VC/WC), 3) apply vertical pressure and rotate 90° clockwise and then counter-clockwise (VCC/WCC). Pain assessment was performed by using the Wong-Baker FACES Pain Rating Scale. Different histamine concentrations were transferred from the well by the Oryum device and applied as WC in section 3. Lancet and Oryum-WP were compared in terms of time and allergen adequacy in section 4. ResultsIn the first section the sensitivity of all techniques for Oryum and lancet were 100%. The false positivity of Oryum-VP, WP and lancet were found 0%. The Oryum-VP technique was found the best for intrapatient coefficient of variation (CV) (10.72%) (p < 0.001). The interpatient CV was similar in the Oryum-VP, VC, VCC and lancet techniques and was different from the Oryum-WP (p < 0.001). In the second section, all Oryum techniques yielded high sensitivities (100%). False-positive results were obtained more in Oryum-WC and WCC. Oryum-WP technique had the lowest pain score. In the 3rd section, the high positive correlation between histamine concentrations was observed (r = 0.731). In terms of time and allergen adequacy, Oryum-WP was superior to the lancet. ConclusionOryum-VP and WP techniques are reliable, tolerable and comparable with the lancet technique.

MALT1 Protease Plays a Dual Role in the Allergic Response by Acting in Both Mast Cells and Endothelial Cells.

The signaling protein MALT1 plays a key role in promoting NF-κB activation in Ag-stimulated lymphocytes. In this capacity, MALT1 has two functions, acting as a scaffolding protein and as a substrate-specific protease. MALT1 is also required for NF-κB-dependent induction of proinflammatory cytokines after FcεR1 stimulation in mast cells, implicating a role in allergy. Because MALT1 remains understudied in this context, we sought to investigate how MALT1 proteolytic activity contributes to the overall allergic response. We compared bone marrow-derived mast cells from MALT1 knockout (MALT1-/-) and MALT1 protease-deficient (MALTPD/PD) mice to wild-type cells. We found that MALT1-/- and MALT1PD/PD mast cells are equally impaired in cytokine production following FcεRI stimulation, indicating that MALT1 scaffolding activity is insufficient to drive the cytokine response and that MALT1 protease activity is essential. In addition to cytokine production, acute mast cell degranulation is a critical component of allergic response. Intriguingly, whereas degranulation is MALT1-independent, MALT1PD/PD mice are protected from vascular edema induced by either passive cutaneous anaphylaxis or direct challenge with histamine, a major granule component. This suggests a role for MALT1 protease activity in endothelial cells targeted by mast cell-derived vasoactive substances. Indeed, we find that in human endothelial cells, MALT1 protease is activated following histamine treatment and is required for histamine-induced permeability. We thus propose a dual role for MALT1 protease in allergic response, mediating 1) IgE-dependent mast cell cytokine production, and 2) histamine-induced endothelial permeability. This dual role indicates that therapeutic inhibitors of MALT1 protease could work synergistically to control IgE-mediated allergic disease.

The suppressive effect of dabrafenib, a therapeutic agent for metastatic melanoma, in IgE-mediated allergic inflammation

The functional inhibition of mast cells, which serve as a key effector cells in allergic reactions may be a specific target for treating immunoglobulin (Ig)E-mediated allergic reactions, which occur in various allergic diseases including anaphylaxis, asthma, and atopic dermatitis. In this study, we demonstrated the effects of dabrafenib, a therapeutic agent used to treat metastatic melanoma, with a focus on mast cell activation and local cutaneous anaphylaxis. In two types of mast cells (RBL-2H3 and mouse bone marrow-derived mast cells), dabrafenib (0.01, 0.1, 1 μM) pretreatment significantly decreased IgE-induced degranulation, intracellular calcium influx, and the activity of intracellular signaling molecules, such as Lyn, Syk, Akt, and PLCγ. Dabrafenib ameliorated mRNA and protein expression levels of interleukin-4 and tumor necrosis factor-α by the reduction of nuclear localization of nuclear factor-κB and nuclear factor of activated T-cells. In passive cutaneous anaphylaxis, oral administration of dabrafenib (0.1, 1, 10 mg/kg) reduced local pigmentation and ear thickness in a dose-dependent manner. Taken together, these results suggest that dabrafenib is a therapeutic drug candidate that controls IgE-mediated allergic inflammatory diseases through suppression of mast cell activity.

Ameliorative effect of selective NLRP3 inflammasome inhibitor MCC950 in an ovalbumin-induced allergic rhinitis murine model

Allergic rhinitis (AR) is a complex IgE-mediated nasal allergic and inflammatory disease. Nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) is essential in the process of allergic and inflammatory responses. MCC950 is a selective NLRP3 inhibitor. However, its role and mechanism in AR remains undetermined. The present study aimed to explore the effect and mechanism of MCC950 on an ovalbumin (OVA) induced mouse model of AR. The AR BALB/c mice were constructed using OVA and administrated intranasally with MCC950. Concentrations of OVA-specific IgE, histamines and leukotrienes C4 (LTC4) in serum, and OVA-specific IgE, ECP, IFN-γ, IL-4, IL-5, IL-13, IL-1β and IL-18 in nasal lavage fluid (NLF) were assayed by enzyme-linked immunosorbent assay (ELISA). Inflammatory cells were counted in NLF. HE and PAS staing were used for evaluating eosinophils and goblet cells. Immunohistochemistry (IHC) staining were employed to evaluate immunolabeling of NLRP3, Caspase-1, ASC, IL-1β and IL-18 in nasal mucosas of mice. Real-time PCR was conducted to assay NLRP3, Caspase-1, ASC, IL-1β and IL-18 mRNA levels. In vitro studies, western blotting, real-time PCR and ELISA were performed to evaluate the effects and mechanisms of OVA and NLRP3 inhibitor MCC950 on spleen mononuclear cells. We found significant downregulation of sneezing, nasal rubbing, inflammatory cytokines, inflammatory cells and NLRP3, Caspase-1, ASC, IL-1β and IL-18 expression in MCC950 treated mice compared with untreated AR mice. In spleen mononuclear cells culture and stimulation experiment, NLRP3, Caspase-1, ASC, IL-1β and IL-18 levels were upregulated by OVA but inhibited by MCC950. In conclusion, MCC950 could effectively exert its ameliorative effect in murine AR by inhibiting NLRP3 and leads to reduction of Caspase-1, ASC, IL-1β and IL-18, resulting in the attenuation of the allergic and inflammatory responses.

Medical thermography in evaluation of results of skin testing by prick test method in patients with IgE-mediated allergic diseases

Objective — to study the aspects of use of medical thermography to evaluate the results of skin testing with allergen solutions in patients with allergic rhinitis, atopic asthma and acute allergic urticaria.Materials and methods. During our study, 40 patients with bronchial asthma and/or allergic rhinitis and/or acute allergic urticaria were examined using a skin prick-test with solutions of diagnostic allergens, followed by visual and thermographic evaluation. The study was open-ended, comparative. Skin testing was performed by standardized prick-test method with domestic allergens manufactured by ME Immunolog (Vinnytsya, Ukraine). Immediately after the visual assessment, an instrumental evalua­tion was performed using a thermograph with a locked image in the memory of the device for further processing.After the initial admission and testing procedure, the antihistamine preparation of bilastine was administered at an average recommended daily dose of 20 mg one tablet per day. After three days (72 hours), all patients were retested with a prick-test method and its visual and thermographic evaluation was performed to determine the degree of suppression of the skin reaction by an antihistamine drug.Results and discussion. Analyzing the comparison of results of visual and thermographic measurements of papule size, we found a high coefficient of correlation between test scores (r = 0.9), but the difference between papule sizes averaged 1.6 mm. However, when analyzing the results, the coincidence of visual analysis by the allergist and thermographic measu­rement accounted for only 70 % of cases.Conclusions. As a result of the analysis and further statistical processing, it was found that the average diameter of the papules of the positive test during the re-examination after taking bilastine decreased by 55.6 % (95 % CI 0.50—0.59). At the same time, in the vast majority (87.2 %) of patients (95 % CI 0.83—0.91), the positive test disappeared completely.

Can atopy have a protective effect against cancer?

BackgroundAn increased prevalence of allergies and an increased incidence of breast cancer have been observed. The hypothesis that atopy may have a protective effect against the risk of different types of breast cancer was evaluated.MethodsIn this study, 11,101 patients (11,101 women with a mean age of 55.2±14.7 years) with different types of breast cancer were tested for allergies. Allergies were confirmed based on the retrospective analysis of allergy diagnostic procedures in patients who had been previously diagnosed with breast cancer. The retrospective prevalence rates of active allergic diseases, including allergic rhinitis, bronchial asthma and atopic dermatitis, were assessed. All patients were also analyzed for bronchial asthma and allergic rhinitis according to the relevant guidelines. A group of healthy control patients was used for the comparisons.ResultsThe women with breast cancer had a significantly lower incidence of IgE-mediated allergic diseases than the controls. The odds ratios (ORs) for allergic rhinitis, atopic dermatitis, and bronchial asthma were 0.61 (95% CI: 0.57–0.73), 0.17 (95% CI: 0.11–0.44), and 0.73 (95% CI: 0.65–0.83), respectively. The mean serum concentrations of total IgE were significantly lower in the study population of women with breast cancer than in the patients of the control group (39.2 ± 26.2 kU/L vs. 108.5 ± 38.5 kU/L; p = 0.002).ConclusionOur results suggest that the overall incidence of allergies, especially allergic rhinitis, is lower in patients with certain types of cancer than in individuals who did not have cancer. Further studies are needed to confirm our findings.

Allergen immunotherapy and asthma.

Allergen immunotherapy (AIT) represents at present the unique disease-modifying treatment strategy for IgE-mediated allergic diseases. AIT can induce clinical improvement of allergic asthma, including reduced symptoms, medication use, and improvement of quality of life, with a long-lasting effect after cessation of treatment. Notably, the current asthma guidelines are now recommending sublingual immunotherapy as an add-on therapy for asthma in adults and adolescents with house dust mite allergy. Clinical indications of AIT, with particular reference to pediatric asthma, mechanisms of clinical and immunological tolerance to allergens, and the potential biomarkers predicting clinical response are discussed.

Sestrin2 Mediates IL-4-induced IgE Class Switching by Enhancing Germline ε Transcription in B Cells

Sestrin2 (Sesn2), a metabolic regulator, accumulates in response to a diverse array of cellular stresses. Sesn2 regulates cellular metabolism by inhibiting the mammalian target of rapamycin complex 1 through the AMP-activated protein kinase (AMPK) signaling pathway. Recently, researchers reported that Sesn2 regulates the differentiation and function of innate immune cells and T cells; however, the role of Sesn2 in B cells is largely unknown. In this study, we investigated the role of Sesn2 in Ig class switching and Ig production in mouse B cells. We observed that mouse B cells express Sesn2 mRNA. Interestingly, the expression of germline ε transcripts (GLTε) was selectively decreased in lipopolysaccharide-stimulated Sesn2−/− splenocytes. Overexpression of Sesn2 increased GLTε promoter activity in B cells. In addition, AICAR (an activator of AMPK) selectively increased IL-4-induced GLTε expression and surface IgE (sIgE) expression in splenocytes. Furthermore, AICAR selectively enhanced IL-4-induced GLTε expression, sIgE expression, and IgE production by anti-CD40-stimulated B cells. We observed that ovalbumin (OVA)-specific IgE concentration was reduced in OVA-challenged Sesn2−/− mice. Taken together, these results indicate that Sesn2-AMPK signaling selectively enhances IL-4-induced IgE class switching and IgE production by B cells, suggesting that this could be a therapeutic strategy targeting Sesn2 in IgE-mediated allergic diseases.

Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.

IgE-mediated allergic disease represents an increasing health problem. Although numerous studies have investigated IgE sequences in allergic patients, little information is available on the healthy IgE repertoire. IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR. Complete VDJ regions were sequenced to near-exhaustion on the PacBio platform. Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs. IgE repertoires appeared to be highly oligoclonal with preferential usage of certain IGHV genes compared to the other isotypes. IgE sequences carried more somatic mutations than IgM, yet fewer than IgG and IgA. Many IgE sequences contained N-linked glycosylation motifs. IgE sequences had no clonal relationship with the other isotypes. The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA. The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens. These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE. This background knowledge may help to elucidate pathogenic mechanisms in allergic disease and to design improved desensitization strategies.

Laboratory Evaluation of Immunotherapy in Treatment of Allergic Airway Diseases

Background: Immunotherapy is a well-established therapeutic approach for treatment of IgE-mediated allergic diseases. It’s the only modality that targets the definite cause of allergy, blocks the pathophysiologic aspect of the disease and possibly prevents the development of a new sensitization. Objective: The aim of this work is evaluation of the response of allergic airway diseases to allergen specific immunotherapy. Patients and methods: We enrolled 50 patients with allergic airway diseasesreceiving subcutaneous immunotherapy (SCIT)shots and 30 control patients on pharmacotherapy. The study evaluated clinical assessment of allergic symptoms, medication used and laboratory markers (including specific and total IgE and eosinophil count) before and after 2 years of immunotherapy. Results: Our results showed that there was a significant decrease in total and specific IgE and eosinophil count after SCIT. Also, SCIT effectively reduced the allergic symptoms and the need for medication. Conclusion: Subcutaneous immunotherapy could alleviate allergic symptoms and reduce airway inflammation in allergic patients.

Laboratory Evaluation of Immunotherapy in Treatment of Allergic Airway Diseases

Background: Immunotherapy is a well-established therapeutic approach for treatment of IgE-mediated allergic diseases. It’s the only modality that targets the definite cause of allergy, blocks the pathophysiologic aspect of the disease and possibly prevents the development of a new sensitization. Objective: The aim of this work is evaluation of the response of allergic airway diseases to allergen specific immunotherapy. Patients and methods: We enrolled 50 patients with allergic airway diseasesreceiving subcutaneous immunotherapy (SCIT)shots and 30 control patients on pharmacotherapy. The study evaluated clinical assessment of allergic symptoms, medication used and laboratory markers (including specific and total IgE and eosinophil count) before and after 2 years of immunotherapy. Results: Our results showed that there was a significant decrease in total and specific IgE and eosinophil count after SCIT. Also, SCIT effectively reduced the allergic symptoms and the need for medication. Conclusion: Subcutaneous immunotherapy could alleviate allergic symptoms and reduce airway inflammation in allergic patients.

The significance of cow’s milk proteins in the development of IgE-mediated food allergy among children

Identification of offending allergens in patients with food allergy is a very important part of an allergist’s activity. Objective. To study the structure оf sensitization to food allergens among children in Moscow and Moscow region and to determine the significance of sensitization to milk proteins . Methods. The level and class of specific IgE in blood serum of children with IgEmediated allergic diseases were examined with RIDA AllergyScreen method. Serum of children with high level of specific IgE to milk allergenic proteins was studied. The level and ratio of specific IgE to individual milk allergens were revealed. Results. The structure of sensitization to food allergens was determined. It was revealed that cow’s milk allergens are the leading triggers of food allergy, especially in early childhood in Moscow and the Moscow region. The features of sensitization to cow’s milk proteins among children were analyzed. Conclusions. According to the study, about half of children with IgEmediated food allergies in Moscow and the Moscow region have sensitization to cow’s milk proteins. The leading role in the frequency of sensitization belongs to whey proteins of milk. Among them sensitization to а-lactalbumin was detected more often. The questions about the selection of hypoallergenic milk formulas for feeding of children with allergy to cow’s milk proteins were discussed.

Development of subcutaneous allergen immunotherapy (part 2): preventive aspects and innovations

Allergen immunotherapy with subcutaneous injection (SCIT) of the relevant allergen is the classic causal treatment method for IgE-mediated allergic respiratory disease and has already been successfully used for over 100 years. This publication is based on a selective literature search in PubMed and MEDLINE. Recent publications in German-language journals that are not available in literature databases were also analyzed. This literature search included original and review articles both in German and in English. Primary, secondary and tertiary prevention characteristics have been demonstrated for SCIT; however, these require further evaluation. In combination with biologic agents, the safety, and in some cases the efficacy, of SCIT can be increased. Adjuvants seem to offer enormous development potential for SCIT. Aluminum salts, microcrystalline tyrosine (MCT), and monophosphoryl lipid A (MPL) are already used in commercial SCIT preparations. At the same time, other adjuvants are being researched, e.g., liposomes, microspheres, CpG motifs (C: nucleotide cytosine, p: phosphate, G: nucleotide guanine), or virus-like particles (VLPs). The therapeutic extracts themselves are also undergoing further development, for instance as recombinant allergens, hypoallergenic variants such as site-directed mutants (SDM), conformational variants, allergen fragmentation, allergen oligomers, deletion mutants, and hybrid allergens/mosaic antigens. SCIT preparations are among the most innovative treatment options in the immunotherapy of allergic diseases. Due to the numerous immunological approaches, they will make treatment safer and more effective in the future with reduced effort.