Molecular Allergy Diagnostics Research Articles

Может ли компонентная аллергодиагностика помочь в установлении траектории формирования «атопического марша»?

Recently, the atopic march (AM) is no longer considered a clear and sequential development of successive allergic diseases, such as atopic dermatitis (AD), asthma, and allergic rhinitis (AR). Recent studies have shown that associations between allergic disorders in children are much more complex, and there may be different variants of AM trajectories. Previously, eight classes of AM were described: (1) no allergic disorders, (2) AM, (3) AD and transient wheeze, (4) AD with later-onset rhinitis, (5) transient wheeze and later-onset rhinitis, (6) transient wheeze only, (7) eczema only, and (8) rhinitis only. 48.3% of children exhibit specific types of sequential development of allergic disorders, but only 7% exhibit profiles resembling ‘classic' AM. The aim of this article was to analyze AM trajectories in real clinical practice in children and to discuss the role of component resolved diagnosis (CRD) in the analysis of AM. The article presents anamnestic patient data and CRD results using a multiplex panel. The literature shows that AM classes do not always match the actual clinical presentation of a patient, indicating the presence of previously unreported AM trajectories. Molecular allergy diagnostics can identify true and cross-sensitization in complex clinical cases, allowing for consideration of the causes of established sensitization and conceptualization of clinical symptoms and individual AM trajectory. It is important to ensure that sensitization to true allergens is established and clinically verified. The analysis of anamnestic data can make it difficult to understand the sequence of allergic disease development. However, CRD significantly facilitates diagnostic search by allowing consideration of the order of sensitization and clinical manifestations. This can help predict the possible severity of allergic reactions to established allergens. KEYWORDS: atopic march, atopic dermatitis, allergic rhinitis, asthma, children, component resolved diagnosis, respiratory allergens. FOR CITATION: Lepeshkova T.S., Andronova E.V. Can component resolved diagnosis help establish "atopic march" trajectory? Russian Medical Inquiry. 2024;8(3):163–170 (in Russ.). DOI: 10.32364/2587-6821-2024-8-3-7.

Клінічна характеристика дітей з персистуючим алергічним ринітом та бронхіальною астмою, сенсибілізованих до різних молекул алергенів кліщів домашнього пилу

Allergic rhinitis (AR) is a disease characterised by different frequency and severity of its course. It has been proven that sensitisation to individual molecules has a different impact on the development of allergy and its clinical manifestations. Modern methods of molecular allergy diagnostics make it possible to determine sensitisation to known and new allergen molecules, including new molecules of HDM - Der p 20 and Der p 21 - in a wide clinical practice. The aim is to identify clinical and anamnestic features in children with AR, taking into account the current spectrum of sensitisation to CDP allergens, to assess the impact of individual (new) HDM allergens on the severity of AR. Materials and methods. Clinical and anamnestic examination of 259 children aged 5-17 years with AR and with a combination of AR and asthma, who were sensitised to HDM allergens, was carried out. Results. The Der p 21 molecule of HDM was more frequently detected in patients with severe AR (35.7%), whereas in children with mild, moderate AR and with a combination of AR and asthma - 21.3-26.2%, but there was no statistical significance in the detected changes. Sensitisation to the new Der p 20 HDM molecule was significantly more frequent in patients with moderate AR (χ2=13.11, p<0.05) compared with patients with mild AR (2.3%). Conclusions. Sensitisation to the new molecule Der p 21 was prevalent in patients with severe AR; sensitisation to Der p 20 was more common in children with moderate and severe AR. Clinicians should consider the presence of sensitisation to new molecules in patients with AR as a possible criterion for predicting the severity of AR. The study was performed in accordance with the principles of the Declaration of Helsinki of the World Medical Association. The protocol of scientific work was approved by the Commission on Bioethical Expertise and Ethics of Scientific Research of the Bogomolets National Medical University (Expert Opinion No. 139 of 26.11.2020) for all patients who participated in the study. The informed consent of patients (parents of children or their guardians) was obtained for the studies. No conflict of interests was declared by the authors.

Hot topics in allergen immunotherapy, 2023: Current status and future perspective.

The importance of allergen immunotherapy (AIT) is multifaceted, encompassing both clinical and quality-of-life improvements and cost-effectiveness in the long term. Key mechanisms of allergen tolerance induced by AIT include changes in memory type allergen-specific T- and B-cell responses towards a regulatory phenotype with decreased Type 2 responses, suppression of allergen-specific IgE and increased IgG1 and IgG4, decreased mast cell and eosinophil numbers in allergic tissues and increased activation thresholds. The potential of novel patient enrolment strategies for AIT is taking into account recent advances in biomarkers discoveries, molecular allergy diagnostics and mobile health applications contributing to a personalized approach enhancement that can increase AIT efficacy and compliance. Artificial intelligence can help manage and interpret complex and heterogeneous data, including big data from omics and non-omics research, potentially predict disease subtypes, identify biomarkers and monitor patient responses to AIT. Novel AIT preparations, such as synthetic compounds, innovative carrier systems and adjuvants, are also of great promise. Advances in clinical trial models, including adaptive, complex and hybrid designs as well as real-world evidence, allow more flexibility and cost reduction. The analyses of AIT cost-effectiveness show a clear long-term advantage compared to pharmacotherapy. Important research questions, such as defining clinical endpoints, biomarkers of patient selection and efficacy, mechanisms and the modulation of the placebo effect and alternatives to conventional field trials, including allergen exposure chamber studies are still to be elucidated. This review demonstrates that AIT is still in its growth phase and shows immense development prospects.

Selected Technical Aspects of Molecular Allergy Diagnostics.

Diagnosis of allergic diseases is a complex, multi-stage process. It often requires the use of various diagnostic tools. The in vitro diagnostics (IVD), which includes various laboratory tests, is one of the stages of this process. Standard laboratory tests include the measurement of the serum concentration of specific immunoglobulin E (sIgE) for selected allergens, full allergen extracts and/or single allergen components (molecules). The measurement of IgE sIgE to the allergen components is called molecular allergy diagnosis. During the standard laboratory diagnostic process, various models of immunochemical tests are used, which enable the measurement of sIgE for single allergens (one-parameter tests, singleplex) or IgE specific for many different allergens (multi-parameter tests, multiplex) in one test. Currently, there are many different test kits available, validated for IVD, which differ in the method type and allergen profile. The aim of the manuscript is to present various technical aspects related to modern allergy diagnostics, especially in the area of molecular allergy diagnostics.

Molecular Allergy Diagnostics in Children with Cow's Milk Allergy: Prediction of Oral Food Challenge Response in Clinical Practice.

Cow's milk allergy (CMA) is the most common food allergy in early childhood. Children with CMA require a precise and punctual diagnosis. Oral food challenge (OFC) is the gold-standard procedure for diagnosing allergies, but it is laborious and requires a particular setting. The aim of the study was to identify the cutoff value of serum allergen-specific IgE values able to predict a positive response to OFC. Children with suspected CMA performed OFC with cow's milk (CM) or derivatives. Total IgE and specific IgE to raw CM, α-lactalbumin, β-lactoglobulin, and casein were measured. Seventy-two children performed OFC, and 30 (41.6%) had a positive response. The significant predictive factors were sensitization to raw CM extract (p = 0.03), α-lactalbumin (p = 0.013), β-lactoglobulin (p = 0.09), and casein (p = 0.019). The cutoff was, respectively: 5.13 kUA/L for raw CM, 1.47 for α-lactalbumin, 1.35 for β-lactoglobulin, and 4.87 for casein. This study allowed us to define a set of cutoff values for CM protein-specific IgE. However, these cutoffs should be interpreted not as a diagnostic tool for CMA but only predictive of response to OFC in a specific territory. Thus, the practical message may be that a value above the cutoff allows a good approximation to identify children to be started on OFC.

An update on the prevalence and diagnosis of cat and dog allergy – Emphasizing the role of molecular allergy diagnostics

The clinical presentation of cat and dog allergy vary from discomfort caused by rhinoconjuncitivitis to severe asthma. Exposure to allergens from these animals is ubiquitous and allergic sensitization to cat or dog affect up to 25% of all children and adults, but allergic sensitization does not always cause symptoms. The introduction of molecular-based allergy diagnostics has improved the possibility to characterize the allergic patient in greater detail. However, the full clinical potential of using molecular allergology in the diagnosis, characterization and treatment of patients with allergy to cats and dogs has not yet been established, although significant progress has been made during the last decade, which will be reviewed in detail in this paper.

Molecular allergy diagnostics in predicting oral cow's milk challenge outcome in Finnish children.

Oral food challenges (OFC) are required to diagnose food allergies but are resource-intensive. To reduce the need for OFCs, we sought to determine serum specific immunoglobulin E (sIgE) cutoff levels for cow's milk and its major allergens predicting oral milk challenge outcomes in children with suspected cow's milk allergy. A total of 135 Finnish children (median age, 1.8 years [range, 1.0-14.1 years]) with suspected cow's milk allergyunderwent open OFC with unheated cow's milk. The sIgE levels to milk (f2), casein (Bos d 8), alpha-lactalbumin (Bos d 4),beta-lactoglobulin (Bos d 5), and bovine serum albumin (BSA) (Bos d 6) were measured and compared with the challenge outcomes. Of the 135 OFCs, 5 were excluded from the study due to purely subjective symptoms. Of the 130 remaining OFCs, 98 results (75%) were positive. In a receiver operating characteristic analysis with 1-2-year-old children, no individual allergen sIgE had a better area under the curve than milk sIgE (0.824). A milk sIgE level > 6.30 kU/L gave 94% specificity and 33% sensitivity for positive OFCs. In 3-14-year-old children, a cutoff value >13.9 kU/L predicted a positive OFC result with 93% specificity and 25% sensitivity. Children with moderate-to-severe reactions had higher sIgE levels to milk, alphalactalbumin, and BSA than did children with mild reactions. Molecular allergy diagnostics did not improve the predictive performance compared with milk sIgE. The milk sIgE value that exceeds the cutoff for 95% specificity in combination with the clinical history may help to reduce the need for OFCs. The severity of an allergic reaction cannot reliably be predicted from sIgE measurements.

Molecular sensitization patterns of common food-and respiratory allergens in the Hungarian population

BackgroundRecently developed Immunoglobulin-E (IgE) based molecular allergy diagnostics provide the ability of identifying allergenic components or ingredients at the molecular level (component-resolved-diagnosis, CRD). Compared to the classical IgE-based allergy diagnostics, molecular technology is providing more sensitive and specific IgE-sensitization patterns. Certain sensitization patterns are characteristic of large geographic regions. There are only few data available on the molecular IgE sensitization patterns in East-Central Europe. This study aims to present further data from this region. MethodsData of 3993 stored, anonymized molecular ImmunoCap IgE measurements (CRD), performed in Hungary between January-December 2019 from sera of 1288 subjects (mean age: 27 years ±18 years, male/female ratio 0.56) were analyzed retrospectively, in order to get a local distributional pattern of the sensitizing (IgE >0.35 KU/l) molecular allergens. ResultsThe proportion of CRD positive cases was 24.3%. Amongst them, the most prevalent inhalative allergens were Amb a 1 (18%) Art v 1 (8%) in adults and Der p 2 (3%) and Der p 1 (3%) and Amb a 1 (4%) in subjects below 18 years of age. The same for food allergens were Gal d 2 (21%), Bos d 4 (17%), Bos d 5 (11%) in adults and Gal d 2 (38%), Gal d 1 (28%), Bos d 4 (21%), Bos d 5 (13%) and Bos d 8 (7%) in children. The ratio of mono-sensitivities among CRD-positive cases was 37.5%. ConclusionOur results provide region-specific patterns of sensitization and molecular allergen spreading for Hungary. The relatively higher abundance of polysensitization's among allergic cases underlines the need for early diagnostic -and preventive measures in the future.

Prevalence of sensitization to molecular food allergens in Europe: A systematic review.

BackgroundRecent reports indicate that the prevalence of food allergy is increasing, but accurate estimates remain a challenge due to cross‐reactivity and limited use of precise diagnostic methods. Molecular allergy diagnostics, in which sensitization to individual molecular allergens is measured, is emerging as a promising tool for evaluation of sensitization profiles. In this systematic review, we summarized estimates of prevalence of sensitization to molecular food allergens in the general population in Europe.MethodsFollowing a protocol prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO; reference CRD42021266657), we searched seven databases with no restrictions on publication date or language. Two reviewers independently screened the literature, extracted data, and appraised the risk of bias in the included studies. The findings were synthesized narratively.ResultsFrom 4776 de‐duplicated records, five studies, with low to moderate overall risk of bias, were included. Forty‐six molecular allergens from 18 foods were investigated. Overall, the prevalence of sensitization was low, particularly for major allergens, and non‐existent for 10 molecular allergens (0% [95% CI 0–0.8]). The highest prevalence was seen for PR‐10 proteins, such as Cor a 1.04 (13.6% [95% CI 10.9–16.9]).ConclusionsAvailable data, primarily from North‐western Europe, indicate that sensitization to molecular food allergens is overall low. The highest estimates were found for cross‐reactive PR‐10 proteins. There were not enough studies to discern regional differences or perform meta‐analysis, highlighting the need for more population‐representative studies in order to elucidate patterns of sensitization to molecular food allergens in Europe.

Allergen-Specific Immunotherapy In Combination With Vitamin D In Patients With Seasonal Allergic Rhinitis

Introduction — Currently, over 500 million people suffer from allergic rhinitis worldwide. For many decades, allergen-specific immunotherapy (ASIT) was the only effective treatment for seasonal allergic rhinitis. The development of molecular allergy diagnostics via ISAC technology allows identifying true and cross-reactive allergens, thereby increasing the information content in selecting an appropriate ASIT. For many years, studies have been conducted on the immunomodulatory effect of vitamin D. These studies revealed the presence of a link between allergic rhinitis and vitamin D deficiency. In this regard, there is a strong need to assess the status of the population in terms of vitamin D for further examination of the effect of the vitamin D inclusion in the treatment regimen on the efficacy of ASIT. Objective — To evaluate the efficacy of ASIT in combination with vitamin D in polysensitized patients with seasonal allergic rhinitis in Karaganda Oblast, Kazakhstan. Material and Methods — Randomized controlled open-label study was conducted during July 2019 – September 2020 at Divera Allergy Center in Karaganda. Patients received sublingual ASIT: the experimental group received ASIT in combination with vitamin D, while comparison group received ASIT in accordance with the standard scheme. Clinical efficacy was monitored by assessing the severity of symptoms and the content of allergen-specific immunoglobulin E. ISAC test was employed to determine the allergen-specific immunoglobulin E. The significance of intergroup differences was determined by statistical methods: the nonparametric Mann-Whitney test for comparing independent groups and the Wilcoxon test for comparing dependent groups. Results — Vitamin D deficiency was revealed in the blood serum of patients in both groups (median value of 16.32 ng/ml and 15.65 ng/ml, respectively). An overall symptom severity score after treatment demonstrated statistically significant changes between the two groups (p=0.777; Mann-Whitney criterion). In the experimental group, the median of overall symptom severity score declined by 46% (from 11 points to 6 points), and in the comparison group by 22% (from 11.5 points to 9 points). Conclusion — As a result of our study, it was established that the adapted scheme of ASIT in combination with vitamin D in polysensitized patients with seasonal allergic rhinitis in Karaganda Oblast (Kazakhstan) was more effective, compared with the conventional scheme of ASIT. Hence, in patients with seasonal allergic rhinitis in the regions with known vitamin D deficiency, it is necessary to determine the vitamin D content with the purpose of its subsequent inclusion in the complex ASIT-based therapy.

Allergic sensitization to lipocalins reflects asthma morbidity in dog dander sensitized children.

BackgroundSensitization to dog is an important risk factor for asthma in children, but the clinical relevance of IgE to available dog‐ and furry animal allergen molecules is uncertain.MethodsSpirometry, methacholine challenge, fraction of exhaled nitric oxide, nasal challenge with dog extract and questionnaires were performed in 59 dog‐sensitized children (age 10–18 years). Serum IgE to dog‐, cat‐, horse extracts and the allergen molecules Can f 1–6, Fel d 1, Fel d 2, Fel d 4 and Equ c 1 were evaluated.ResultsMedian numbers of positive IgE results to furry animal allergen molecules among children without asthma was 3, with asthma 5.5 and with troublesome asthma 9 (asthma vs. no asthma; p = 0.039; troublesome asthma vs. no asthma; p = 0.009). The odds ratio for asthma if sensitized to any lipocalin was 7.2 (95% confidence Interval: 1.44–35.9). Children with troublesome asthma had higher IgE levels to the lipocalins Can f 2, Can f 4 and Can f 6 compared to the rest of the study population (44 vs. 4.1 kUA/L, p = 0.015; 5.8 vs. 0.9 kUA/L, p = 0.018 and 1.3 vs. 0.7 kUA/L, p = 0.03 respectively). Furthermore, a positive nasal challenge was more common among children with troublesome asthma (83% vs. 36%, p = 0.036).ConclusionsPolysensitization to furry animal allergens and lipocalins is associated with asthma in dog‐sensitized children. Children with troublesome asthma have higher IgE levels to several dog lipocalins than other dog sensitized children.Key messagePolysensitization to furry animal allergens and high IgE levels to the dog lipocalins Can f 2, Can f 4 and Can f 6 is associated with asthma severity in dog dander sensitized children. Molecular allergy diagnostics may thus help the clinicians to evaluate the impact of allergic sensitization on asthma morbidity.

Determination of co-sensitization is an important step in improving the effectiveness of allergen-specific immunotherapy in patients with pollen disease

In order to increase the effectiveness of allergen-specific immunotherapy in patients with pollen disease, the profile of allergen sensitization was determined at the molecular level, performed in 47 patients with clinical manifestations of seasonal rhinoconjunctivitis and perennial allergic rhinitis during a long time period. Allergic examination of patients included history taking, molecular blood tests using ALEX technology to determine the level of specific antibodies class lgE of major and minor components of pollen and household allergens and diagnostic skin tests (pre-test). Assessment of the main clinical manifestations of allergic rhinitis was performed according to the recommendations of the European Association of Allergists and Immunologists. The severity of nasal symptoms was determined by the TNSS scale, and ocular symptoms - by the TOSS scale. Integral assessment of the intensity of clinical symptoms of allergic rhinitis was calculated as the sum of scores by the main symptoms. According to the results of molecular allergy diagnostics, the profile of allergic sensitization in patients with pollen disease was determined, which established the presence of specific lgE - antibodies to major allergy components of ragweed pollen (nAmb a1) – in 91.5±4.1% of patients, wormwood (nArt v3, nArt v1) – in 40.4±7.2%, meadow thyme (rPh1 p1, rPh1 p5b) – in 17.0±5.5%, house dust mites (Der p1, Der p2) – in 29.8±6,7%. Developed on the basis of molecular allergy diagnostics, the profile of allergological sensitization to allergocomponents allows to obtain complete and detailed information on patient sensitization (diagnose a real allergy), cross-reactivity to other allergens, justify the feasibility and predict the effectiveness of allergen-specific immunotherapy.

Методи мультикомпонентного (мультиплексного) імуноаналізу специфічних IGE до алергокомпонентів у хворих на IGE-залежну алергію

Abstract. Component-resolved diagnostics or molecular allergy diagnostics has found application in the practice of an allergist. It is used to map a patient’s allergenic sensitization at the molecular level, using purified natural or recombinant allergenic molecules in place of extracts. Multiplex methods for determining the concentration of specific IgE in the blood serum allow to characterize the repertoire of IgE sensitization of the patient, to create an allergological «passport» of the patient. There are ISAC (Immuno Solid-Phase Allergen Chip — ISAC), which includes the determination of IgE to 112 allergens and ALEX2 (Allergy Explorer — ALEX2), which includes the determination of IgE to 295 allergens.

Ребенок с пищевой анафилаксией. Как обеспечить полноценное питание?

This article presents a modern approach to developing a balanced personalized diet for a child with polyvalent food allergy and history of severe life-threatening allergic reactions, based on the results of molecular allergy diagnostics. Providing an adequate and safe nutrition for children who have experienced episodes of food-induced anaphylaxis becomes a serious problem for their family. This article describes the continuation of observation of a five-year-old patient with polyvalent food allergy and recurrent episodes of food-induced anaphylaxis. According to the component-resolved allergy diagnostics, it was found that the child was sensitized to many food allergens: milk and egg proteins, wheat, beans, peanuts, nuts, fruits, and some other products that make up a healthy diet. Based on the findings, a safe and balanced personalized elimination diet was developed with a specialized amino acid-based formula, which is presented in this publication. Key words: food anaphylaxis, children, polyvalent allergy, recurrent anaphylaxis, nutrition

Ефективність алергенспецифічної імунотерапії пилковими алергенами в дітей із позиції молекулярної алергології

Мета роботи — встановити можливі причини неефективності алергенспецифічної імунотерапії (АСІТ) пилковими алергенами (бур’янів) у дітей із сезонним алергічним ринітом і/або бронхіальною астмою на підставі вивчення гіперчутливості до алергенів, аналізу анамнестичних даних. Матеріали та методи. Проведено алерготестування 192 дітей. 52 пацієнтам проведене анамнестичне опитування з акцентом на перехресну алергію та супутню патологію верхніх дихальних шляхів, а також на ефективність АСІТ. Статистична обробка результатів проведена в програмі Statistica for Windows 6.0. Результати. Серед хворих на поліноз переважала гіперчутливість до амброзії (56 %), циклахени (46 %) та соняшника (58 %). До злакових рослин (райграс, грястиця, вівсяниця) чутливі 10—20 % пацієнтів. 23 % дітей мають сенсибілізацію до 5 та більше алергенів (в середньому до 3,3 ± 0,4). 52 % дітей мають супутню харчову алергію, 15 % — синдром оральної алергії, третина дітей — аденоїдні вегетації, гіпертрофію глоткових мигдалин, у 13 % алергічний риніт ускладнювався синуситом. Незадовільний клінічний ефект АСІТ пилковими алергенами асоціювався з наявністю поєднаної пилково-грибкової сенсибілізації, перехресної харчової та пилкової алергії, із сенсибілізацією до 4 та більше пилкових алергенів, з полівалентною алергією, а також спостерігався при поєднанні алергічного риніту із синуситом (р < 0,05). Висновки. Перед початком АСІТ дітям із полінозами необхідно визначити групу ризику стосовно можливої неефективності цього методу терапії та рекомендувати їм визначення специфічних імуноглобулінів класу Е до мажорних та мінорних алергенів для прогнозування ефективності АСІТ.

Significance of molecular diagnostics in allergen immunotherapy : Practical tips for the application in various groups of allergens with exemplary cases

The basis of allergen immunotherapy (AIT) is the diagnosis of the eliciting allergen sources, which is achallenge, especially in the case of multiple sensitizations. Molecular allergy diagnostics can be of special help, since detection of "marker allergens", usually important major allergens, allows to distinguish between primary sensitization and cross-reactions. Thus, the indication and extract selection for AIT can be facilitated. While molecular diagnosis is particularly useful for double-sensitized hymenoptera venom and polysensitized pollen allergic patients, the benefit is probably lower in case of house dust mite allergy.

96 Sublingual allergen-specific immunotherapy in pediatric patients: biomarkers and molecular allergy diagnostics as predictors of therapeutic success

Abstract Background Efficacy of allergen-specific immunotherapy (ASIT) in patients with asthma could be significantly enhanced when physicians have an opportunity to identify those who are most likely to respond, determine when to stop treatment, and predict relapse. Thus, molecular allergy diagnostic is an effective tool that could help to individualize the diagnosis and treatment of asthma by accurate detection of the causative and cross-reactive allergens in pediatric patients. Cytokines are known as reliable diagnostic and prognostic biomarkers for asthma and can be used to evaluate the therapeutic effect. Objectives To evaluate the roles of molecular allergy diagnostic and biomarkers (L-10, IFNγ и TGFβ) as predictors of ASIT efficacy in pediatric patients with asthma. Design/Methods Eighty children aged 5 to 18 years with mild and moderate atopic bronchial asthma were included in the study. Sixty-eight out of 80 (85%) were found to have sensitization to house dust mites Dermatophagoides Pteronyssinus and/or Dermatophagoides Farinae. All these patients underwent molecular diagnostics using ImmunoCAP (Phadia 100) to determine the major (r Der p1, r Der p 2) and minor allergens (r Der p10) of the house dust mites. Twenty-eight patients with mild and moderate asthma were found to have a high sensitivity to these allergens and received SLIT with a mixture of house dust mites (Dermatophagoides Pteronyssinus and/or Dermatophagoides Farinae). To compare the efficacy of SLIT, we evaluated the severity of asthma clinical symptoms on a point scale from 0 to 3, and biomarker levels (IL-10, IFNγ и TGFβ) before and 6 months after SLIT. Twelve healthy children were included in the study as a reference group. Results At the beginning of the study, the average daily score in the SLIT group of 2.5 ± 0.7, and after 6 months of treatment, it decreased to 0.5 ± 0.2. The levels of biomarkers were markedly decreased prior to the treatment, especially TGFβ levels, and normalized at the end of treatment (Tab.1). Conclusion These findings support the efficacy of molecular diagnosis to determine the efficacy of allergen-specific immunotherapy in patients with asthma.

Молекулярная аллергодиагностика и оптимизация аллергенспецифической иммунотерапии при сенсибилизации к пыльце сорных трав

Молекулярная аллергодиагностика и оптимизация аллергенспецифической иммунотерапии при сенсибилизации к пыльце сорных трав

Molecular Allergy Diagnostics Refine Characterization of Children Sensitized to Dog Dander

To analyze patterns of immunoglobulin E (IgE) reactivity to dog allergen components in sensitized children and investigate the association between those patterns and clinical symptoms by nasal provocation tests (NPT).Children 10 to 18 years (n = 60) with known sensitization to dog identified by a skin prick test wheal >3 mm or serum-specific IgE >10 kU/L were included.NPTs were performed with a commercial dog extract by using a standardized protocol. The extract was analyzed by radioallergosorbent test inhibition and contained all 6 dog allergens (Can f 1, 2, 3, 4, 5, and 6) used in subsequent analyses. The allergens were present in a wide range of concentrations. Serum-specific IgE levels to dog extract and each of the allergenic components were measured.All but 2 children had allergic rhinitis or conjunctivitis, and 41 out of 60 (68%) reported symptoms with dog exposure. The mean serum-specific IgE level was 11.5 kU/L (interquartile range: 3.15–43.0 kU/L). Sensitization to Can f 1 was most common, followed in frequency by Can f 5, 4, 6, 2, and 3. There was a wide range of IgE levels to the components, with the highest levels to Can f 1, 2, and 5. History of dog-related rhinitis was most common among those sensitized to Can f 3 (94% vs 59% of those not sensitized, P = .012) and Can f 6 (86% vs 63%, P = .007). Similar associations were found for histories of dog-induced asthma. Most patients were sensitized to several components, with great overlap in their sensitization to the proteins belonging to different groups (lipocalins: Can f 1, 2, 4, and 6; serum albumin: Can f 3; and prostatic kallikrein: Can f 5). No single protein group was associated with history of dog-induced airway symptoms, but sensitization to more proteins increased the odds ratio (OR) of dog-induced asthma or rhinitis. Those sensitized to all proteins from all 3 groups were at higher risk of dog-induced rhinitis (OR: 8.36; 95% confidence interval: 1.0–69.5). Forty-two percent (25 out of 60) of patients had positive NPT results, 14 out of 60 (23%) had inconclusive NPTs, and 21 out of 60 (35%) had negative challenges. Those with positive NPT results were significantly more likely to report dog-induced rhinitis and asthma as compared with those with negative NPT results. After adjusting for the effects of different protein groups, only sensitization to the lipocalins (Can f 1, 2, 4, and 6) was associated with positive NPT results. Those sensitized to all 3 groups had the highest OR for a positive NPT result, but as with reported symptoms above, sensitization to increasing numbers of proteins was associated with increasing risk for a positive NPT result.Sensitization to lipocalins and to an increasing number of allergenic dog proteins is associated with dog-induced airway symptoms (dog allergy).“I am not allergic to my dog, but other dogs bother me.” My dog is “hypoallergenic.” How many times have we heard comments like these from patients? Every study that has tried to identify allergenic differences between breeds of dogs has failed to find that elusive hypoallergenic dog. In fact, there is great homology of Can f 1 (the major dog allergen) among breeds. Furthermore, all breeds have comparable amounts of airborne Can f 1 in the homes of dog owners. So, what is going on here? The answer might lie in component-resolved diagnostics (CRD). Commercially available CRDs have already helped our understanding of some food allergies by enhancing our ability to make accurate diagnoses of allergy in sensitized patients. Options for follow-up studies to this one are obvious. Do different breeds of dog produce varying amounts of individual or total lipocalins? Are some patients more highly sensitized to particular proteins or more types of proteins, placing them at differential risk of allergy to certain breeds? Or, are some less highly sensitized, making them more tolerant of different breeds? When those questions are answered and when CRDs for dog allergens are commercially available, we still might not identify a consistently less-allergenic dog. But, we might be able to identify the breeds most likely to be tolerated by a child sensitized to dog.

Molecular allergy diagnostics as a predictor of efficacy of sublingual allergen-specific immunotherapy in pediatric patients

Molecular allergy diagnostics as a predictor of efficacy of sublingual allergen-specific immunotherapy in pediatric patients