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1.
J Investig Allergol Clin Immunol ; 34(3): 157-166, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38888580

ABSTRACT

BACKGROUND AND OBJECTIVE: Sensitization to Blomia tropicalis is associated with asthma in various tropical and subtropical countries; however, information about the specific molecular components associated with this disease is scarce. Using molecular diagnosis, we sought to identify B tropicalis allergens associated with asthma in Colombia. METHODS: Specific IgE (sIgE) to 8 B tropicalis recombinant allergens (Blo t 2, 5, 7, 8, 10, 12, 13, and 21) was determined using an in-house ELISA system in asthma patients (n=272) and controls (n=298) recruited in a national prevalence study performed in several Colombian cities (Barranquilla, Bogotá, Medellín, Cali, and San Andrés). The study sample included children and adults (mean [SD] age, 28 [17] years). Cross-reactivity between Blo t 5 and Blo t 21 was evaluated using ELISA-inhibition. RESULTS: Specific IgE (sIgE) to 8 B tropicalis recombinant allergens (Blo t 2, 5, 7, 8, 10, 12, 13, and 21) was determined using an in-house ELISA system in asthma patients (n=272) and controls (n=298) recruited in a national prevalence study performed in several Colombian cities (Barranquilla, Bogotá, Medellín, Cali, and San Andrés). The study sample included children and adults (mean [SD] age, 28 [17] years). Cross-reactivity between Blo t 5 and Blo t 21 was evaluated using ELISA-inhibition. CONCLUSION: Although Blo t 5 and Blo t 21 are considered common sensitizers, this is the first report of their association with asthma. Both components should be included in molecular panels for diagnosis of allergy in the tropics.


Subject(s)
Allergens , Asthma , Immunoglobulin E , Humans , Asthma/immunology , Asthma/diagnosis , Asthma/epidemiology , Immunoglobulin E/immunology , Immunoglobulin E/blood , Adult , Male , Female , Case-Control Studies , Child , Adolescent , Colombia/epidemiology , Allergens/immunology , Young Adult , Middle Aged , Antigens, Plant/immunology , Cross Reactions , Tropical Climate , Prevalence , Child, Preschool
2.
Adv Respir Med ; 92(3): 218-229, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38921061

ABSTRACT

Ragweed pollen allergy is the most common seasonal allergy in western Romania. Prolonged exposure to ragweed pollen may induce sensitization to pan-allergens such as calcium-binding proteins (polcalcins) and progression to more severe symptoms. We aimed to detect IgE sensitization to recombinant Amb a 9 and Amb a 10 in a Romanian population, to assess their potential clinical relevance and cross-reactivity, as well as to investigate the relation with clinical symptoms. rAmb a 9 and rAmb a 10 produced in Escherichia coli were used to detect specific IgE in sera from 87 clinically characterized ragweed-allergic patients in ELISA, for basophil activation experiments and rabbit immunization. Rabbit rAmb a 9- and rAmb a 10-specific sera were used to detect possible cross-reactivity with rArt v 5 and reactivity towards ragweed and mugwort pollen extracts. The results showed an IgE reactivity of 25% to rAmb a 9 and 35% to rAmb a 10. rAmb a 10 induced basophil degranulation in three out of four patients tested. Moreover, polcalcin-negative patients reported significantly more skin symptoms, whereas polcalcin-positive patients tended to report more respiratory symptoms. Furthermore, both rabbit antisera showed low reactivity towards extracts and showed high reactivity to rArt v 5, suggesting strong cross-reactivity. Our study indicated that recombinant ragweed polcalcins might be considered for molecular diagnosis.


Subject(s)
Calcium-Binding Proteins , Cross Reactions , Immunoglobulin E , Rhinitis, Allergic, Seasonal , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Cross Reactions/immunology , Rhinitis, Allergic, Seasonal/immunology , Rhinitis, Allergic, Seasonal/blood , Romania , Calcium-Binding Proteins/immunology , Antigens, Plant/immunology , Allergens/immunology , Female , Male , Ambrosia/immunology , Rabbits , Adult , Plant Extracts
3.
Dermatol Reports ; 16(1): 9819, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38623363

ABSTRACT

Acute or chronic infections have been described among causes of chronic urticaria (CU). Anisakidosis is a human disease caused by the ingestion of larval nematodes of the family Anisakidae. The infestation is acquired by eating raw seafood or undercooked fish and squid. There are considerable variations in the frequency of underlying causes in the different studies and in different countries, such as differences in diets and the prevalence of infections. Anisakis simplex has been recognized as a trigger of both acute and CU manifestations. However, there is still a lack of evidence about its management and treatment in dermatology. We, therefore, reviewed some biologic properties of Anisakis simplex in order to understand the relationship between its biology and the mechanism it uses to establish chronic dermatological conditions such as urticaria and cause late complications. In addition, we herein report some concerns about the effectiveness of systemic treatment in preventing complications and management in dermatological settings.

4.
Mol Immunol ; 161: 11-24, 2023 09.
Article in English | MEDLINE | ID: mdl-37480600

ABSTRACT

PURPOSE OF REVIEW: This review evaluates the current modes of allergen-specific immunotherapy for cockroach allergens, in terms of clinical outcomes and explores future trends in the research and development needed for a more targeted cockroach immunotherapy approach with the best efficacy and minimum adverse effects. SUMMARY: Cockroach allergy is an important risk factor for allergic rhinitis in the tropics, that disproportionately affects children and young adults and those living in poor socio-economic environments. Immunotherapy would provide long-lasting improvement in quality of life, with reduced medication intake. However, the present treatment regime is long and has a risk of adverse effects. In addition, cockroach does not seem to have an immuno-dominant allergen, that has been traditionally used to treat allergies from other sources. Future trends of cockroach immunotherapy involve precision diagnosis, to correctly identify the offending allergen. Next, precision immunotherapy with standardized allergens, which have been processed in a way that maintains an immunological response without allergic reactions. This approach can be coupled with modern adjuvants and delivery systems that promote a Th1/Treg environment, thereby modulating the immune response away from the allergenic response.


Subject(s)
Cockroaches , Drug-Related Side Effects and Adverse Reactions , Rhinitis, Allergic , Child , Humans , Young Adult , Animals , Quality of Life , Desensitization, Immunologic , Rhinitis, Allergic/therapy , Allergens
5.
Mol Nutr Food Res ; 67(16): e2200601, 2023 08.
Article in English | MEDLINE | ID: mdl-37173826

ABSTRACT

SCOPE: Red meat, a staple food of Western diets, can also induce IgE-mediated allergic reactions. Yet, apart from the heat-labile protein serum albumin and the carbohydrate α-Gal, the molecules causing allergic reactions to red meat remain unknown. METHODS AND RESULTS: IgE reactivity profiles of beef-sensitized individuals are analyzed by IgE-immunoblotting with protein extracts from raw and cooked beef. Two IgE-reactive proteins are identified by peptide mass fingerprinting as myosinlight chain 1 (MYL1) and myosin light chain 3 (MYL3) in cooked beef extract and are designated Bos d 13 isoallergens. MYL1 and MYL3 are produced recombinantly in Escherichia coli. ELISAs proved their IgE reactivity and circular dichroism analysis showed that they represent folded molecules with remarkable thermal stability. In vitro gastrointestinal digestion experiments showed the higher stability of rMYL1 as compared to rMYL3. Exposure of a monolayer of Caco-2 cells to rMYL1 indicated that the molecule is able to cross intestinal epithelial cells without disturbing the integrity of the tight junctions, suggesting the sensitizing capacity of MYL1. CONCLUSION: MYLs are identified as novel heat-stable bovine meat allergens.


Subject(s)
Allergens , Food Hypersensitivity , Humans , Cattle , Animals , Food Hypersensitivity/etiology , Hot Temperature , Caco-2 Cells , Immunoglobulin E , Meat/analysis , Cross Reactions
6.
Article in English | MEDLINE | ID: mdl-36811838

ABSTRACT

BACKGROUND AND OBJECTIVES: Blomia tropicalis sensitization is associated with asthma in different tropical and sub-tropical countries; however, information about the specific molecular components associated with this disease is scarce. Using molecular diagnosis, we sought to identify B. tropicalis allergens associated with asthma in Colombia. METHODS: Specific IgE (sIgE) to eight B. tropicalis recombinant allergens (Blo t 2/5/7/8/10/12/13 and 21) was determined using an in-house developed ELISA system in asthmatic patients (n=272) and control subjects (n=298) recruited in a national prevalencestudy performed in Colombian cities (Barranquilla, Bogotá, Medellín, Cali and San Andrés). Sample study included children and adults (mean age: 28±SD 17 years old). Cross-reactivity between Blot 5 and Blo t 21 was evaluated by ELISA-inhibition. RESULTS: Sensitization to Blo t 21 (aOR: 1.9; 95% CI: 1.2 - 2.9) and Blo t 5 (aOR: 1.6; 95%CI: 1.1 - 2.5), but not Blo t 2, was associated with asthma. sIgE levels to Blo t 21 and to Blo t 5 were significantly higher in the disease group. Cross-reactivity between Blo t 21 and Blo t 5 is on average moderate; however, individual analysis indicates that may be high (>50%) in some cases. CONCLUSIONS: Although Blo t 5 and Blo t 21 has been described as common sensitizers, this is the first report of their association with asthma. Both components should be included in molecular panels for allergy diagnosis in the tropics.

7.
Clin Mol Allergy ; 20(1): 11, 2022 Sep 14.
Article in English | MEDLINE | ID: mdl-36104791

ABSTRACT

BACKGROUND: Allergy to Apis dorsata (Giant Asian Honeybee) venom is the commonest insect allergy in Sri Lanka and South East Asia. However, laboratory diagnosis is difficult as the pure venom and diagnostic reagents are not commercially available. OBJECTIVE: This study assessed the use of four recombinant allergens of A. mellifera venom and the passive basophil activation test in the diagnosis of A. dorsata venom anaphylaxis. METHODS: Serum IgE levels to four recombinant allergens of A. mellifera, rApi m 1, 2, 5 and 10 were assessed and compared with serum IgE to the crude venom of A. mellifera or V. vulgaris by Phadia ImmunoCAP, in patients who developed anaphylaxis to A. dorsata stings. Basophil activation in response to venom of A. dorsata or V. affinis was assessed using a passive basophil activation test. Association of the severity of the reaction with basophil activation was compared. RESULTS: rApi m 1 and 10 combinedly had significant correlation (r = 0.722; p < 0.001) with the crude venom of A. mellifera (Western honeybee) and a higher positivity rate of 90% (27/30). Whereas, IgE reactivity to rApi m 2 or 5 had significant correlation (p = 0.02 and p = 0.005 respectively) with V. vulgaris crude venom. All 30 (100%) were positive to A. dorsata venom in passive BAT; 70% (21/30) had over 80% activation, 96.7% (29/30) had over 60% activation and 100% had over 50% activation. Percentage activation of basophils in patients who had mild or moderate reactions (n = 20) was significantly low (p = 0.02) from that of patients who had severe reactions (n = 10). CONCLUSIONS: rApi m 1 and 10 when combined was sensitive for the diagnosis of A. dorsata allergy. This combination had the lowest cross-reactivity rate with Vespula vulgaris. The passive BAT is highly sensitive in A. dorsata allergy. The basophil reactivity was significantly higher in severe anaphylaxis compared to mild/moderate anaphylaxis. This finding should be further explored in further studies.

8.
Clin Chim Acta ; 535: 112-119, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-36030884

ABSTRACT

BACKGROUND: ALEX multiplex platform has been recently commercialized but its clinical utility as quantitative technique respect to ImmunoCAP-singleplex as the reference method has not yet been confirmed on patients suffering from nut allergy and co-sensitization to different nuts. METHODS: 58 serum samples from patients with nut allergy from a Mediterranean population were assayed in parallel by ALEX-multiplex and ImmunoCAP-singleplex techniques. Patients were diagnosed based on clinical symptoms and positive skin prick tests (SPTs). The following whole extracts were compared between both techniques: walnut, hazelnut, peanut, almond, pistachio and sunflower seed; besides the recombinant Pru p 3. A qualitative and quantitative study was carried out. RESULTS: Both techniques had similar sensitivities respect to whole extracts from walnut, hazelnut and peanut as well as to Pru p 3 (p > 0.05). However for whole extracts from almond, pistachio and sunflower seed the sensitivity obtained by ALEX was much lower than ImmunoCAP (9.09 % vs 88.63 %; 14.81 vs 70.37 %; and 8.51 % vs 88.88 %; respectively). The concordance between both techniques showed only a substantial agreement for Pru p 3 (k = 0.791); moderate agreement for hazelnut and peanut (k = 0.550 and k = 0.544, respectively); fair agreement for walnut (k = 0.386) and poor agreement for almond, pistachio and sunflower seed (k < 0.2). Quantitative analysis showed that ImmunoCAP for walnut, peanut and sunflower seed had higher mean values than ALEX. Relationships were significant for all specific IgE levels except to for almond, pistachio and sunflower seed. CONCLUSIONS: ALEX platform is a suitable technique to patients with nut allergy from the Mediterranean area except to for those suffering from allergy to almond, pistachio and sunflower seed.

9.
Int Arch Allergy Immunol ; 183(3): 315-321, 2022.
Article in English | MEDLINE | ID: mdl-34700320

ABSTRACT

INTRODUCTION: There is limited knowledge on the sensitization patterns to peanut proteins and food allergy in the Middle East. The objective of this study is to analyze the relationship between sensitization patterns to peanut proteins and clinical symptoms in a group of patients with physician-diagnosed peanut allergy (PA) in Kuwait. METHODS: PA patients were evaluated by the skin prick test (SPT), serum total IgE, peanut-specific IgE (sIgE), and sIgE against Ara h 1-3, 8, and 9, and clinical data were collected. RESULTS: Sixty-nine patients were included. A positive correlation between peanut SPT and sIgE was detected for all 3 storage proteins (Ara h 1-3) in patients <6 years old and for Ara h 1 and 2 in older patients. ROC analysis of positive correlations showed that oral food challenge should be considered for definite diagnosis of PA only if the level of Ara h 2 is <22.25 KUA/L, with level of Ara h 2 ≥15.4 allowing the detection of systemic reactions with a sensitivity of 55.56%. Patients presenting with systemic reactions more frequently had positive Ara h 1 (88.9%) and Ara h 2 (83.3%), compared with 44.1% and 52.9% in those with local reaction (p = 0.0046 and p = 0.0378). The levels of Ara h 1 and 2 were also significantly higher in patients with systemic reactions compared to those with a local reaction, with those differences being especially relevant for Ara h 2 (15.9 vs. 0.4) (p = 0.0005). CONCLUSIONS: The pattern of sensitization to peanut proteins in the Middle East is similar to that of the Western world. Measurement of sIgE antibodies to Ara h 1, 2, and 3 is useful in the diagnosis of PA and in the investigation of reactions to raw and roasted peanuts.


Subject(s)
Arachis , Peanut Hypersensitivity , 2S Albumins, Plant , Aged , Allergens , Antigens, Plant , Child , Humans , Immunoglobulin E , Kuwait/epidemiology , Peanut Hypersensitivity/diagnosis , Peanut Hypersensitivity/epidemiology
10.
Hautarzt ; 72(11): 1003-1013, 2021 Nov.
Article in German | MEDLINE | ID: mdl-34652490

ABSTRACT

Anaphylaxis is a suddenly occurring potentially life-threatening systemic allergic reaction. In childhood, food allergens play a major role but insect stings and drugs are also potential triggers. The symptoms appear in minutes up to few hours on the skin, airways, gastrointestinal tract and/or the cardiovascular system. Intramuscular adrenaline is the drug of first choice due to its rapid effectiveness and its low side effect potential. A detailed patient history and the determination of potential IgE antibodies must be carried out to identify the triggers. The register for anaphylaxis has improved knowledge on epidemiology. An education in anaphylaxis is useful for every patient as well as parents and caregivers. Allergen-specific immunotherapy is currently the only causal treatment option; however, at the present time it is only available for insect bites and peanut allergy.


Subject(s)
Anaphylaxis , Food Hypersensitivity , Insect Bites and Stings , Adolescent , Allergens , Anaphylaxis/diagnosis , Anaphylaxis/therapy , Desensitization, Immunologic , Epinephrine , Food Hypersensitivity/diagnosis , Food Hypersensitivity/therapy , Humans , Insect Bites and Stings/diagnosis , Insect Bites and Stings/therapy
11.
Hautarzt ; 72(9): 751-759, 2021 Sep.
Article in German | MEDLINE | ID: mdl-34383107

ABSTRACT

The basis of allergen immunotherapy (AIT) is the diagnosis of the eliciting allergen sources, which is a challenge, 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.


Subject(s)
Allergens , Hypersensitivity , Desensitization, Immunologic , Humans , Hypersensitivity/diagnosis , Hypersensitivity/therapy , Immunoglobulin E , Pathology, Molecular
13.
Int Arch Allergy Immunol ; 182(7): 637-641, 2021.
Article in English | MEDLINE | ID: mdl-33839729

ABSTRACT

INTRODUCTION: Weed pollen allergy is an important and in prevalence increasing cause of pollinosis in Europe and across the world. In this study we focus on the value of common diagnostic tools for detection of a sensitization to mugwort and English plantain, especially with regard to the clinical relevance of the sensitization. METHODS: Eighty weed pollen sensitized patients (41 to mugwort and 39 to English plantain) were assessed retrospectively regarding their clinical anamnesis, in-vivo tests (skin prick test [SPT] and allergen specific provocation) and in-vitro tests (immunoglobulin E [IgE] reactivity to purified natural allergen extract and specific allergen components in serum). RESULTS: 85% of mugwort and 83% of English plantain sensitizations could be diagnosed by SPT alone. Distinction between allergic and non-allergic patients could be made with clinical challenges solely. IgE serology revealed IgE antibodies against the native pollen extracts for mugwort in 98% and for English plantain in 90% of patients. Detection of major allergens nArt v 1, nArt v 3 and Pla l 1 did not add accuracy to the diagnosis. A vast majority of the weed pollen allergic patients was sensitized to >1 allergen. Minor allergens were found to be of less importance. CONCLUSION: The exact diagnosis of weed pollen allergy can be challenging due to confounding components in anamnesis and diagnostic tests. IgE-serology does not delineate allergic from sensitized patients. Component resolved diagnostics (CRD) can confirm, but not replace, extract based diagnostic methods, such as SPT, provocation tests or serology to native extracts. Hence, these are the gold standard diagnostic tools in weed pollen allergy up to now.


Subject(s)
Allergens/immunology , Plant Weeds/adverse effects , Pollen/immunology , Rhinitis, Allergic, Seasonal/epidemiology , Rhinitis, Allergic, Seasonal/immunology , Antigens, Plant/immunology , Humans , Immunization , Immunoglobulin E/blood , Immunoglobulin E/immunology , Rhinitis, Allergic, Seasonal/diagnosis , Skin Tests
14.
Int Arch Allergy Immunol ; 182(2): 120-130, 2021.
Article in English | MEDLINE | ID: mdl-32942277

ABSTRACT

INTRODUCTION: Sensitization to Aspergillus fumigatus is a risk factor for severe asthma. However, little is known about its presence, appearance, and impact on allergic rhinitis. Herein, we investigated the usefulness of component resolved diagnostics in patients sensitized to Aspergillus fumigatus protein extract. METHODS: Seventy-eight patients with suspected allergic rhinitis and elevated IgE levels toward Aspergillus fumigatus protein extract were retrospectively evaluated regarding their total and Aspergillus-specific IgE levels and their skin prick test. Furthermore, they were tested for specific IgE antibodies against Asp f 1, 2, 3, 4, and 6. RESULTS: Skin prick test missed 6 patients (7.7%) with elevated IgE toward Aspergillus fumigatus protein extract. Fifty percent of patients (n = 39) were sensitized to at least one component. Even though monosensitization affected all components, all patients with positivity toward more than one component were sensitized to Asp f 1. There was a statistically significant increase of Aspergillus-specific IgE with increasing number of components affected by sensitization. Many patients were oligo- (34.6%) or polysensitized (51.3%). There was a high prevalence of sinusitis (61.8%). CONCLUSIONS: Component resolved diagnostic testing toward the major allergen Asp f 1 was less sensitive than skin prick test and serology to Aspergillus fumigatus protein extract. However, sensitivity of component resolved diagnostics might be underestimated. Diagnostics of the species-specific allergens Asp f 1, 2, and 4 might allow to differentiate between genuine and cross-reactive sensitization. In the clinical routine, skin prick test and serology to crude extract remain the methods of choice.


Subject(s)
Aspergillosis/diagnosis , Aspergillosis/microbiology , Aspergillus fumigatus , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Allergens/immunology , Antibody Specificity , Antigens, Fungal/immunology , Aspergillus fumigatus/immunology , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Male , Middle Aged , Rhinitis, Allergic/diagnosis , Rhinitis, Allergic/immunology , Skin Tests , Young Adult
15.
J Biol Regul Homeost Agents ; 34(5): 1729-1737, 2020.
Article in English | MEDLINE | ID: mdl-33143407

ABSTRACT

Molecular characterization of IgE reactivity of specific individual components of allergenic extracts is now possible due to the technology of recombinant allergens derived from studies of molecular biology of allergic pathology. The identification of the immunoreactivity to single allergenic components in allergic subjects allows to specifically define her/his allergic profile and obtain the so-termed Component Resolved Diagnosis (CRD). Molecular allergens can be classified into those that induce the respiratory allergic reactivity and those that identify the food-related allergic pathology. It is also essential to identify those molecular allergens whose immunoreactivity is able to connect the two clinical conditions: respiratory symptoms and food allergy symptoms. The present study was conducted on 50 patients with a clinical history of hypersensitivity to pollen and/or allergy and positivity to Skin Prick Test. The sera were analyzed in our laboratories and the panel of recombinant allergens was applied in the case of positivity of the specific IgE. Of the 50 patients enrolled, 31 were selected as positive to 4 main pan-allergen Bet v1, Par j2, Art v1 and Phl p1; among these, 14 subjects showed one allergen-specific IgE towards natural extracts of tested foods even in absence of clinical history. CRD allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in: a) resolving genuine vs cross-reactive sensitization in poly-sensitized patients, b) assessing, in selected cases, the risk of severe, systemic vs mild, local reactions in food allergy, and c) identifying patients and triggering allergens for specific immunotherapy (ITS). In light of our results, we believe that the transition from a diagnostic based on the use of allergenic extracts to another one based on the use of single allergenic molecules that is able to define the specific allergenic profile of each patient, seems to be able to revolutionize the allergy diagnosis.


Subject(s)
Allergens , Female , Food Hypersensitivity/diagnosis , Humans , Immunoglobulin E , Male , Pollen/immunology , Skin Tests
16.
Article in German | MEDLINE | ID: mdl-33095280

ABSTRACT

Currently, extract-based therapeutic allergens from natural allergen sources (e.g., house dust mites, tree and grass pollen) are used for allergen-specific immunotherapy (AIT), the only causative therapy that can exhibit positive disease-modifying effects by tolerance induction and prevention of disease progression. Due to variations in the natural composition of the starting materials and different manufacturing processes, there are variations in protein content, allergen composition, and allergenic activity of similar products, which poses specific challenges for their standardization. The identification of the nucleotide sequences of allergenic proteins led to the development of molecular AIT approaches. This allows for the application of exclusively relevant structures as chemically synthesized peptides, recombinant single allergens, or molecules with hypoallergenic properties that potentially allow for an up-dosing with higher allergen-doses without allergic side effects leading more quickly to effective cumulative doses. Further modifications of AIT preparations to improve allergenic and immunogenic properties may be achieved, e.g., by including the use of virus-like particles (VLPs). To date, the herein described therapeutic approaches have been tested in clinical trials only. This article provides an overview of published molecular approaches for allergy treatment used in clinical AIT studies. Their added value and challenges compared to established therapeutic allergens are discussed. The aim of these approaches is to develop highly effective and well-tolerated AIT preparations with improved patient acceptance and adherence.


Subject(s)
Allergens , Hypersensitivity , Desensitization, Immunologic , Germany , Humans , Hypersensitivity/therapy , Immunotherapy , Peptides
17.
Int J Mol Sci ; 21(14)2020 Jul 16.
Article in English | MEDLINE | ID: mdl-32708567

ABSTRACT

Hypersensitivity or an allergy to chicken egg proteins is a predominant symptomatic condition affecting 1 in 20 children in Australia; however, an effective form of therapy has not yet been found. This occurs as the immune system of the allergic individual overreacts when in contact with egg allergens (egg proteins), triggering a complex immune response. The subsequent instantaneous inflammatory immune response is characterized by the excessive production of immunoglobulin E (IgE) antibody against the allergen, T-cell mediators and inflammation. Current allergen-specific approaches to egg allergy diagnosis and treatment lack consistency and therefore pose safety concerns among anaphylactic patients. Immunotherapy has thus far been found to be the most efficient way to treat and relieve symptoms, this includes oral immunotherapy (OIT) and sublingual immunotherapy (SLIT). A major limitation in immunotherapy, however, is the difficulty in preparing effective and safe extracts from natural allergen sources. Advances in molecular techniques allow for the production of safe and standardized recombinant and hypoallergenic egg variants by targeting the IgE-binding epitopes responsible for clinical allergic symptoms. Site-directed mutagenesis can be performed to create such safe hypoallergens for their potential use in future methods of immunotherapy, providing a feasible standardized therapeutic approach to target egg allergies safely.


Subject(s)
Egg Hypersensitivity/diagnosis , Egg Hypersensitivity/therapy , Immunotherapy/methods , Allergens/immunology , Animals , Egg Hypersensitivity/immunology , Egg Proteins/immunology , Epitopes/immunology , Humans , Immunoglobulin E/immunology
18.
J Allergy Clin Immunol ; 146(5): 1097-1108, 2020 11.
Article in English | MEDLINE | ID: mdl-32298697

ABSTRACT

BACKGROUND: House dust mites (HDMs) are among the most important allergen sources containing many different allergenic molecules. Analysis of patients from a double-blind, placebo-controlled allergen-specific immunotherapy (AIT) study indicated that patients may benefit from AIT to different extents depending on their molecular sensitization profiles. OBJECTIVE: Our aim was to investigate in a real-life setting whether stratification of patients with HDM allergy according to molecular analysis may enhance AIT success. METHODS: Serum and nasal secretion samples from patients with HDM allergy (n = 24) (at baseline, 7, 15, 33, and 52 weeks) who had received 1 year of treatment with a well-defined subcutaneous AIT form (Alutard SQ 510) were tested for IgE and IgG reactivity to 15 microarrayed HDM allergen molecules with ImmunoCAP Immuno-solid-phase Allergen Chip technology. IgG subclass levels to allergens and peptides were determined by ELISA, and IgG blocking was assessed by basophil activation. In vitro parameters were related to reduction of symptoms determined by combined symptom medication score and visual analog scale score. RESULTS: Alutard SQ 510 induced protective IgG mainly against Dermatophagoides pteronyssinus (Der p) 1 and Der p 2 and to a lesser extent to Der p 23, but not to the other important allergens such as Der p 5, Der p 7, and Der p 21, showing better clinical efficacy in patients sensitized only to Der p 1 and/or Der p 2 as compared with patients having additional IgE specificities. CONCLUSION: Stratification of patients with HDM allergy according to molecular sensitization profiles and molecular monitoring of AIT-induced IgG responses may enhance the success of AIT.


Subject(s)
Antigens, Dermatophagoides/immunology , Arthropod Proteins/immunology , Cysteine Endopeptidases/immunology , Desensitization, Immunologic/methods , Hypersensitivity/therapy , Immunoglobulin E/metabolism , Immunoglobulin G/metabolism , Plant Extracts/therapeutic use , Adult , Animals , Epitopes/immunology , Female , Humans , Hypersensitivity/immunology , Injections, Subcutaneous , Male , Protein Array Analysis , Pyroglyphidae
19.
J Allergy Clin Immunol ; 146(4): 894-900.e2, 2020 10.
Article in English | MEDLINE | ID: mdl-32259540

ABSTRACT

BACKGROUND: We recently reported that 16 weeks of sublingual immunotherapy (SLIT) with recombinant (r) Mal d 1, but not rBet v 1, significantly improved birch pollen-related apple allergy. Allergen-specific IgE-blocking IgG antibodies have been associated with clinical efficacy. OBJECTIVE: We compared the quantity, quality, and IgE-blocking bioactivity of SLIT-induced Mal d 1-specific IgG antibodies in both treatment groups. METHODS: Pre- and post-SLIT sera were assessed for rMal d 1-specific IgG antibodies in ELISA and for their ability to inhibit apple allergen-induced upregulation of CD63 on basophils from nontreated individuals with birch pollen-related apple allergy. Post-SLIT sera depleted of IgG1 or IgG4 were compared for their IgE-blocking activity. IgG1 binding to rMal d 1 was competed with rMal d 1 and rBet v 1 in ELISA. RESULTS: SLIT with rMal d 1 and rBet v 1 induced comparable levels of rMal d 1-specific IgG1, IgG2, IgG3, and IgG4 antibodies. Only post-rMal d 1 SLIT sera displayed IgE-blocking activity, which was significantly reduced by depletion of IgG1 and less so by IgG4 depletion. In competition ELISA, IgG1 binding to Mal d 1 in post-rMal d 1 SLIT sera was fully inhibited with rMal d 1 but not with rBet v 1. Correspondingly, Bet v 1 was the more potent competitor for IgG1 binding to Mal d 1 in post-rBet v 1 SLIT sera. CONCLUSION: rMal d 1 SLIT for 16 weeks induced functional, primarily Mal d 1-specific IgE-blocking antibodies, whereas rBet v 1 SLIT induced Bet v 1-specific, Mal d 1-cross-reactive IgG antibodies with limited cross-blocking activity. These results provide a possible explanation for the limited effectiveness of birch pollen immunotherapy in birch pollen-related food allergy and indicate a dominant protective role of functional IgE-blocking IgG1 antibodies in the early phase of allergy treatment.


Subject(s)
Allergens/immunology , Antibodies, Blocking/immunology , Antigens, Plant/immunology , Food Hypersensitivity/immunology , Immunoglobulin E/immunology , Malus/adverse effects , Plant Proteins/immunology , Antibodies, Blocking/blood , Antibody Specificity/immunology , Basophils/immunology , Basophils/metabolism , Female , Food Hypersensitivity/diagnosis , Food Hypersensitivity/therapy , Humans , Immunoglobulin E/blood , Immunoglobulin G/immunology , Male , Protein Binding , Recombinant Proteins , Sublingual Immunotherapy , Treatment Outcome
20.
Curr Allergy Asthma Rep ; 20(4): 9, 2020 03 06.
Article in English | MEDLINE | ID: mdl-32144500

ABSTRACT

PURPOSE OF REVIEW: Focusing on the strict relationship between house dust mites and crustaceans from the allergenic point of view. RECENT FINDINGS: The well-known tropomyosin was considered for years as the cross-reacting allergen between shrimp and house dust mites. In the last few years, several allergens not only in shrimps but also in house dust mite have been identified and other molecules other than tropomyosin have been shown to cross-react between crustaceans and mites. The present review investigates the very complex allergen sources in shrimp and mites, giving a satisfactorily complete picture of the interrelationships between common allergens. Several minor HDM allergens are homologous to major and minor shrimp allergens; tropomyosin is not the only cross-reactive allergen between shrimp and mites.


Subject(s)
Allergens/immunology , Antigens, Dermatophagoides/immunology , Arthropod Proteins/immunology , Decapoda/immunology , Pyroglyphidae/immunology , Animals , Cross Reactions/immunology , Humans , Tropomyosin/immunology
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