Allergic IgE Research Articles

Clonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy

Allergic disease reflects specific inflammatory processes initiated by interaction between allergen and allergen-specific IgE. Specific immunotherapy (SIT) is an effective long-term treatment option, but the mechanisms by which SIT provides desensitization are not well understood. Our aim was to characterize IgE sequences expressed by allergen-specific B cells over a 3-year longitudinal study of patients with aeroallergies who were undergoing SIT. Allergen-specific IgE-expressing clones were identified by using combinatorial single-chain variable fragment libraries and tracked in PBMCs and nasal biopsy samples over a 3-year period with antibody gene repertoire sequencing. The characteristics of private IgE-expressing clones were compared with those of stereotyped or "public" IgE responses to the grass pollen allergen Phleum pratense (Phl p) 2. Members of the same allergen-specific IgE lineages were observed in nasal biopsy samples and blood, and lineages detected at baseline persisted in blood and nasal biopsy samples after 3 years of SIT, including B cells that express IgE. Evidence of progressive class switch recombination to IgG subclasses was observed after 3 years of SIT. Acommon stereotyped Phl p 2-specific antibody heavy chain sequence was detected in multiple donors. The amino acid residues enriched in IgE-stereotyped sequences from seropositive donors were analyzed with machine learning and k-mer motif discovery. Stereotyped IgE sequences had lower overall rates of somatic hypermutation and antigen selection than did single-chain variable fragment-derived allergen-specific sequences or IgE sequences of unknown specificity. Longitudinal tracking of rare circulating and tissue-resident allergen-specific IgE+ clones demonstrates persistence of allergen-specific IgE+ clones, progressive class switch recombination to IgG subtypes, and distinct maturation of a stereotyped Phl p 2 clonotype.

YKL-40 as a possible marker of neutrophilic asthma.

Asthma is a heterogeneous chronic disorder of the airways, with inflammation and bronchial hyperresponsiveness as its major underlying phenomena. Asthmatics vary in terms of inflammation pattern, concomitant pathologies, and factors aggravating the course of the disease. As a result, there is a need for sensitive and specific biomarkers that could facilitate diagnosing asthma as well as phenotyping in everyday practice. Chitinases and chitinase-like proteins (CLPs) seem promising in this field. Chitinases are evolutionarily conserved hydrolases that degrade chitin. In contrast, CLPs bind chitin but do not have degrading activity. Mammalian chitinases and CLPs are produced by neutrophils, monocytes, and macrophages in response to parasitic or fungal infections. Recently, several questions have been raised about their role in chronic airway inflammation. Several studies demonstrated that overexpression of CLP YKL-40 was associated with asthma. Moreover, it correlated with exacerbation rate, therapy resistance, poor control of symptoms, and, inversely, with FEV1. YKL-40 facilitated allergen sensitization and IgE production. Its concentration was elevated in bronchoalveolar lavage fluid after an allergen challenge. It was also found to promote the proliferation of bronchial smooth muscle cells and correlate with subepithelial membrane thickness. Thus, it may be involved in bronchial remodeling. Associations between YKL-40 and particular asthma phenotypes remain unclear. Some studies showed that YKL-40 correlates with blood eosinophilia and FeNO, suggesting a role in T2-high inflammation. Quite the opposite, cluster analyses revealed the highest upregulation in severe neutrophilic asthma and obesity-associated asthma. The main limitation in the practical application of YKL-40 as a biomarker is its low specificity. High serum levels of YKL-40 were also found in COPD and several malignancies, in addition to infectious and autoimmune diseases. To conclude, the level of YKL-40 correlates with asthma and some clinical features in the whole asthmatic population. The highest levels are found in neutrophilic and obesity-related phenotypes. However, due to its low specificity, the practical application of YKL-40 remains uncertain but could be useful in phenotyping, especially when combined with other biomarkers.

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.

A new trend in sensitization to cockroach allergen: A cross-sectional study of indoor allergens and food allergens in the inland region of Southwest China.

Despite the increasing prevalence of allergic disease, large-scale studies to investigate allergen sensitization have rarely been conducted in the inland region of Southwest China. This study aimed to investigate the trend of allergen sensitization in mainland China from 2016 to 2017. During the 2-year study period, from 2016 to 2017, the serum samples of 7,759 allergic patients collected from 38 hospitals in Yunnan were detected the specific immunoglobulin E (sIgE) against 8 indoor and food allergens, namely, house dust mite, cockroach, dog dander, mold mix, egg white, milk, crab, and shrimp. The polysensitization patterns were analyzed through cluster analysis, and the relationship between cockroach and other indoor and food allergens was analyzed. Allergen sIgE positivity was prevalent in 45.6% of the population. Cockroach was the most common allergen (27.0%), followed by house dust mite (25.6%), shrimp (18.8%) and crab (15.6%). Three polysensitization clusters were identified: cluster 1): egg white/milk; cluster 2): crab/shrimp/cockroach/house dust mite/dog dander; and cluster 3): mold mix. The sIgE levels and sensitization rates to house dust mite, crab, and shrimp increased with the level of cockroach sIgE (P < 0.05). Based on big data in the real world, we found that there is a new trend in common allergens in Southwest China, where house dust mite is the only available reagent of specific immunotherapy. Cockroaches may become another major allergen in mainland China in the future, and clinicians should be aware of this.

EFFECT OF OMALIZUMAB ON VENOM SPECIFIC IGE AND VENOM SKIN TESTING

<h3>Introduction</h3> Omalizumab, a monoclonal IgG antibody which binds free IgE, is indicated for the treatment of chronic spontaneous urticaria, uncontrolled nasal polyps, and moderate to severe asthma with perennial allergic sensitization. This case illustrates the effect of omalizumab on venom-specific IgE and percutaneous testing. <h3>Case Description</h3> A 48 year old female with severe persistent asthma on omalizumab for six years experienced wheezing and throat swelling within two hours of a suspected hymenoptera sting. Evaluation while patient remained on omalizumab included venom serology obtained two weeks after sting, which was positive only to paper wasp and white-faced hornet, and percutaneous testing three months after sting to honeybee, yellow jacket, and yellow hornet, which was negative through 0.1 ug/mL intradermals, at which time testing was stopped due to systemic reaction. After holding omalizumab for sixteen weeks, repeat percutaneous testing was performed but confounded by dermatographism; repeat venom serology revealed increased specific IgE to all tested hymenoptera except honeybee. <h3>Discussion</h3> To our knowledge, this is the first report describing omalizumab's effect on venom-specific IgE levels and percutaneous testing. Given previous studies that have suggested omalizumab does not convert specific IgE for environmental allergens from positive to negative, it is important for allergists to be aware of omalizumab's potential to suppress venom-specific IgE and skin test reactivity. If a patient on omalizumab with concern for venom hypersensitivity has negative serologic or percutaneous testing to hymenoptera, consideration should be given to repeating testing after omalizumab has been discontinued for four to five half-lives.

Sensitization to Furry Animals in Patients with Suspected Allergic Disease in China: A Multicenter Study.

An objective of this study was to investigate the allergen sensitization characteristics of cat, dog and horse dander in patients with suspected allergic diseases in different geographical regions of Chinese mainland. We invited 2377 patients aged 0-86 years with suspected allergic diseases to participate in a cross-sectional survey in 11 provinces in China. Combined with the questionnaires and animal-specific IgE levels, we analyzed the epidemiological characteristics and risk factors of furry animal sensitization in different regions and populations of Chinese Mainland. Among the 2377 patients with suspected allergic diseases, 14.9% were sensitized to cat dander, 9.3% to dog dander and 5.5% to horse dander. Animal allergens mainly cause low-level sensitization (class 1-3). There was a significant correlation between cat, dog and horse dander allergen sIgE, with correlation coefficients (rs) all greater than 0.750. The majority (46.5%) of sIgE-positive patients were sensitized to at least two animal allergens simultaneously. The prevalence of these animals all showed a trend of increasing first and then decreasing with age, and all reached the peak in young adolescence. As for the geographical factors, the sensitization rate of cats and dogs in Western was significantly higher than that in Eastern (cat: 18.4% vs 9.2%, dog: 11.6% vs 5.5%, all P < 0.001), however, no significant differences were found in horses. Aged ≤6 years, living in Western, and high animal allergen exposure elevated the risk of cat or dog sensitization. Living on a lower floor (aOR: 0.56) was a protective factor for horse sensitization. In this representative sample of Chinese patients with suspected allergic diseases, there was an apparent geographic variation in sensitization to cats and dogs. Age factor and living in Western also had a significant impact on animal allergen sensitization rate.

Potential allergenicity and hydrolysis assessment of bovine casein and β-casein by treatment with lactic acid bacteria.

Casein is one of the main allergens in cow's milk, accounting for 80% of cow's milk proteins. The ability of hydrolyzing proteins by bacteria is also different. In this study, the capacity of lactic acid bacteria to hydrolyze casein or β-casein and the IgG/IgE-binding capacity of hydrolysates were evaluated. The intensity of casein and β-casein degradation was analyzed by SDS-PAGE and RP-HPLC. The hydrolysates were tested for their capacity to inhibit IgG and IgE binding by ELISA. The peptides in the hydrolysate were also analyzed by LC-MS/MS. In these strains, Lactobacillus rhamnosus (CICC No. 22175) had the strongest hydrolysis of casein and β-casein. The hydrolysate of Lactobacillus rhamnosus (CICC No. 22175) showed the lowest antigenicity and potential allergenicity. It also hydrolyzed major allergen IgE epitopes and preserved T cell epitopes. Thereore Lactobacillus rhamnosus (CICC No. 22175) could be used for developing hypoallergenic dairy products and the development of tolerance. PRACTICAL APPLICATIONS: By the study, it obtained that a strain of Lactobacillus rhamnosus could effectively degrade casein and reduced the potential allergenicity of casein. At the same time, some major allergic epitopes were hydrolyzed and T cell epitopes were preserved. Therefore, it is very valuable for the application and development of lactic acid bacteria. The hydrolysate can also be used in a new hypoallergenic dairy formula with specific health benefits and promoting oral tolerance.

A CASE OF NEAR-FATAL ASTHMA EXACERBATION

A CASE OF NEAR-FATAL ASTHMA EXACERBATION

Algorithm for selecting patients for house dust mite allergen specific immunotherapy in children with bronchial asthma and allergic rhinitis

Objective. Based on literature data and own research, on the selection of pediatric patients for the treatment of allergen immunotherapy (AIT) with house dust mite (HDM) allergens, to develop an Algorithm for selecting patients for AIT with HDM allergens in children with bronchial asthma (BA) and allergic rhinitis (AR). &#x0D; Methods. Data from our own studies included 420 patients with AR and complaints indicating domestic sensitization (256 boys, 164 girls), aged 5 to 17,.9 years (mean age 8,.44 ± 3.,06), of which 176 have had BA. Patients underwent skin prick tests (SPT) with household allergens, determination of sIgE for HDM allergens by the ImmunoCAP method, and nasal provocative test (NPT) with HDM. If the results were negative, the allergological examination was repeated again in 12-–18 months. &#x0D; Results: The Patient Selection Algorithm was constructed on the basis of the obtained data on the significance of the examination methods used. The primary role of SPT, the possibility of repeating the examination in case of negative results, indications for NPT with HDM allergens were taken into account. The algorithm makes it possible to organize an examination of a patient with HDM allergy in order to develop indications for AIT.

In vitro-induced Foxp3+ CD8+ regulatory T cells suppress allergic IgE response in the gut.

Several subsets of CD8+ T cells are known to have a suppressive function in different tissues and diseases in mice and humans. Due to the lack of a consensus on the phenotype of regulatory CD8+ T cells and very low frequency in the body, its clinical use as adoptive cellular therapy has not advanced much. In the present work, using DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (Aza), we efficiently and stably differentiated naïve CD8+ T cells (CD8+ CD25- CD44- cells) into the CD8+ Foxp3+ regulatory CD8+ T cells (CD8 Tregs). We also generated OVA peptide257-264 -specific CD8+ Foxp3+ Tregs. Compared with activated CD8 T cells, Aza plus TGF-β-induced CD8+ Foxp3+ Tregs showed significantly increased surface expression of CD39, CD73, CD122, CD62L, and CD103, and secreted TGF-βand suppressed the proliferation of effector CD4+ T cells. Interestingly, CD8+ Foxp3+ Tregs exhibited low expression of perforin and granzyme required for cytotoxic function. Analysis of chemokine receptors showed that TGF-β+Aza induced CD8+ Foxp3+ Tregs expressed gut-tropic chemokine receptors CCR6 and CCR9, and chemokine receptors CCR7 and CXCR3 required for mobilization into the spleen, lymph nodes, and gut-associated lymphoid tissues. Adoptive transfer of induced CD8+ Foxp3+ Tregs restored cholera toxin-induced breakdown of oral tolerance to OVA by regulating OVA-specific IgE and IgG1. Altogether, we showed an efficient method to generate antigen-specific CD8+ Foxp3+ Tregs, and the adoptive transfer of these cells induces oral tolerance by suppressing allergic response and maintaining intestinal homeostasis.

Eczema phenotypes and IgE component sensitization in adolescents: A population-based birth cohort

BackgroundEczema patients are commonly immunoglobulin (Ig)E polysensitized. Although atopic dermatitis (AD) phenotypes have been recognized, IgE sensitization patterns based on AD phenotypes have not been well illustrated. We aimed to investigate how eczema phenotypes impact IgE component sensitization patterns. MethodsThis birth cohort study investigated a general population in the Tokyo Children's Health, Illness, and Development Study (T-Child Study) until children reached the age of 13 years. Eczema was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Allergen component specific IgE antibody titers were measured using a multiplex array ImmunoCAP ISAC. ResultsPersistent eczema phenotype until adolescence was strongly associated with allergic march symptoms, such as wheezing and hay fever, and oral allergy symptoms, and IgE component sensitizations of airborne (Japanese cedar, house dust mite, Timothy, cat, and dog) and cross-reactive allergens (Bet v 1 family) compared to early-remission and late-onset eczema. On the other hand, late-onset eczema did not show any strong associations with allergic symptoms and IgE sensitization. Adolescents with persistent eczema have high comorbidity of symptoms of pollen-food allergy syndrome. ConclusionsEarly-onset eczema is deeply connected with the later allergic march, and late-onset eczema differs from the phenotype of allergic march. Early-onset eczema characterizing IgE sensitization was likely to be an extrinsic type, and late-onset eczema, which was not related to IgE sensitization, was likely an intrinsic type. Pollen-Food Allergy Syndrome is one of the allergic features in allergic march.

Art v 1 IgE epitopes of patients and humanized mice are conformational

Worldwide, pollen of the weed mugwort (Artemisiavulgaris) is a major cause of severe respiratory allergy, with its major allergen, Art v 1, being the key pathogenic molecule for millions of patients. Humanized mice transgenic for a human T-cell receptor specific for the major Art v 1 T-cell epitope and thecorresponding HLA have been made. We sought to characterize IgE epitopes of Art v 1-sensitized patients and humanized mice for molecular immunotherapy of mugwort allergy. Four overlapping peptides incorporating surface-exposed amino acids representing the full-length Art v 1 sequence were synthesized and used to search for IgE reactivity to sequential epitopes. For indirect mapping, peptide-specific rabbit antibodies were raised to block IgE against surface-exposed epitopes on folded Art v 1. IgE reactivity and basophil activation studies were performed in clinically defined mugwort-allergic patients. Secondary structure of recombinant (r) Art v 1 and peptides was determined by circular dichroism spectroscopy. Mugwort-allergic patients and humanized mice sensitized by allergen inhalation showed IgE reactivity and/or basophil activation mainly to folded, complete Art v 1 but not to unfolded, sequential peptide epitopes. Blocking of allergic patients' IgE with peptide-specific rabbit antisera identified a hitherto unknown major conformational IgE binding site in the C-terminal Art v 1 domain. Identification of the new major conformational IgE binding site on Art v 1, which can be blocked with IgG raised against non-IgE reactive Art v 1 peptides, is an important basis for the development of a hypoallergenic peptide vaccine for mugwort allergy.

The Mediating Effect of Cytokines on the Association between Fungal Sensitization and Poor Clinical Outcome in Asthma.

Sensitization to fungal allergens is one of the proposed phenotypes in asthma. An association between fungal sensitization and worse clinical outcomes is apparent. Moreover, fungal sensitization in asthma that is associated with different type of immunological mechanism has been reported. How the role of cytokines mediates the association between fungal sensitization and poorer asthmatic outcomes remains unclear. We aimed to determine role of cytokines in the relationship between fungal sensitization and worse clinical outcomes in asthma. Method: We conducted a prospective study to recruit adult patients with asthma. Data including age, sex, height, weight, smoking history, medication, emergency visit and admission, pulmonary function testing result, and Asthma Control Test (ACT) scores were collected. We used the automated BioIC method to measure fungal allergen sIgE in sera. Serum levels of Interleukin (IL) -4, IL-13, IL-6, IL-9, IL-10, IL-17 A, IL-22, Interferon (IFN) -γ, Immunoglobulin E (IgE), Tumor necrosis factor-α (TNF-α), and Transforming growth factor-β (TGF-β) were measured using ELISA. Result: IL-6 and IL-17A had a significant positive correlation between sensitization and most fungi species compared to IgE. Sensitization to Candida albicans had strongly positive association both with IL-6 and IL-17A. However, only IL-17A had significant relationship with ED visit times. The mediation analysis result indicates that IL-17A had a significant positively mediating effect (ME) on the association between Candida albicans and ED visit times. Conclusion: IL-17A is a potential mediator to link Candida albicans sensitization and ED visits for asthma. We suggest that patients with fungal sensitization, such as Candida albicans, have poorer outcomes associated with Th17-mediated immune response rather than Th2.

Analysis of specific sIgE detection of house dust mites and aspergillus fumigatus in 2 535 patients with respiratory allergic diseases and respiratory infectious diseases in the Guangzhou area

Objective: To compare the specific IgE positive rates of the patients between allergic respiratory diseases and respiratory infectious diseases in Guangzhou, the relationship between the co-sensitization of house dust mite (HDM) allergen and Aspergillus fumigatus (AF) allergen and asthma, allergic rhinitis with asthma, pneumonia, upper respiratory infections, bronchitis, serum total immunoglobulin E (total Immunoglobulin E, tIgE) and age were analyzed, to provide the basis for the prevention and treatment of respiratory allergic diseases and respiratory infectious diseases in this area. Methods: A total of 2 535 patients with confirmed respiratory allergic diseases and respiratory infectious diseases were selected retrospectively from the outpatient or inpatient department of the First Affiliated Hospital of Guangzhou Medical University from April 2017 to June 2021 and detected HDM and AF specific IgE (sIgE) by the ImmunoCAP system. The age range was 1 to 89 years. The median age was 5 years. The average age was 9. ≤3 years old group n=894, 4-6 years old group n=721, 7-18 years old group n=615, 19-49 years old group n=207, >49 years old group n=98. There were 1 596 males (62.96%) and 939 females (37.04%). There were 1 279 cases of allergic diseases and 1 256 cases of respiratory infectious diseases. The different disease groups were divided into asthma group (411 cases), allergic rhinitis group (458 cases), allergic rhinitis combined with asthma group (410 cases), pneumonia group (463 cases), upper respiratory tract infection group (299 cases) and bronchitis group (494 cases). The difference of specific IgE (sIgE) and tIgE between HDM and AF was analyzed. For statistical analysis, continuous variables were tested by Mann-Whitney U. Classification data by chi-square test or Fisher's exact test. Results: 1 313 (51.79%) patients were sIgE positive for HDM allergen, 65 (2.56%) were sIgE positive for AF allergen, and 50 (1.97%) were both positive. In the respiratory allergic disease group, 877 cases (68.57%,877/1 279) were positive for HDM allergen sIgE, 57 cases (4.46%,57/1 279) were positive for AF allergen sIgE, and 44 cases (3.44%,44/1 279) were both positive; 436 cases (34.71%,436/1 256) of respiratory infectious diseases were positive for HDM allergen sIgE, 8 cases (0.64%,8/1 256) were positive for AF allergen sIgE, and 6 cases (0.48%,6/1 256) were both positive. In monosensitization, the HDM allergen sIgE sensitization rate was the highest in the allergic rhinitis & asthma group, at 80.24% (329/410). The positive rate of HDM allergen sIgE in male patients was 53.76%(858/1 596), and the positive rate in female patients was 46.22%(434/939), and the difference between the two was statistically significant (χ2=13.449, P<0.001). In polysensitization, asthma patients (5.35%,22/411) had the highest positive rate of HDM sensitization with AF, followed by allergic rhinitis patients (3.06%,14/458), allergic rhinitis with asthma (1.95%,8/410). The positive rate of respiratory infectious diseases such as pneumonia (0.43%,2/463), upper respiratory infections (0.33%,1/299), and bronchitis (0.61%,3/494) with AF was extremely low. The positive rate of HDM combined with AF in infants(≤3 years old group,0.34%, 3/894; 4-6 years old group, 0.97%, 7/721)was significantly lower than that in teenagers and adults(7-18 years old group,3.58%, 22/615; 19-49 years old group,6.28%, 13/207;>49 years old group,5.10%, 5/98).In the patients with HDM and AF combined sensitization, HDM sIgE levels were distributed in all grades, and AF sIgE levels were mainly in grades 1, 2, and 3. Conclusion: The positive rate of HDM combined with AF was higher in patients with respiratory allergic diseases such as asthma, allergic rhinitis, and allergic rhinitis combined with asthma, suggesting that clinical attention should be paid to the combination of HDM and AF in patients with asthma and allergic rhinitis, especially adults, more likely to be combined with AF.

Characteristics and changes of sensitization patterns of major allergens in children from 2010 to 2020 in a hospital of pediatric in Beijing

Objective: To analyze the sensitization characteristics and change of major allergens in children from 2010 to 2020 in Beijing, so as to provide basis for diagnosis, treatment and prevention of allergic diseases in children. Methods: A retrospective study was conducted to analyze the children who were suspected of allergic diseases and tested for serum immunoglobulin E (total IgE and specific IgE) in the children's Hospital Affiliated to the Capital Institute of Pediatrics from January 2010 to December 2020. A total of 45 746 children aged 0-17 years in Beijing were enrolled with a median (interquartile range) of 3.8 (2.5, 5.3) years. There were 28 918 boys (63.2%) and 16 828 girls (36.8%) and 14 984 cases (32.8%) in the infant group (<3 years old), 22 049 cases (48.2%) in the preschool group (3-6 years old), and 8 713 cases (19.0%) in the school-age group (6 years old and above). Immunocap allergen detection system (fluorescence enzyme-linked immunosorbent assay) was used to detect and the characteristics and change trend of allergens during 11 years were statistically analyzed by Chi square test. Results: The top three positive rates of single food allergens sIgE were egg white 42.6% (2 788/6 577 tests), milk 38.4% (2 606/6 782 tests) and wheat 31.8% (1 417/4 449 tests), and the sequence of single inhaled allergens were Ragweed 42.6% (440/1 034 tests), Artemisia 38.4% (1 045/3 191 tests) and Alternaria alternata 31.3% (3 358/10 725 tests). The positive detection rates of egg white 47.0%(1 904/4 048 tests), milk 41.9%(1 769/4 226 tests) and wheat 33.9%(973/2 870 tests) in the infant group were the highest, and there have statistically significant(χ2=91.495, 73.907, 16.966, P<0.05). The positive rates of fx1 (22.5%, 121/537 tests), peanut (24.9%, 111/446 tests), soybean (20.0%, 74/370 tests) and shrimp (7.48%, 44/588 tests) were the highest in the school-age group(χ²=14.436, 10.751, 11.569, 13.703, P<0.05). The most common inhaled allergens were Alternaria alternata (14.8%, 422/2 859 tests) in the infant group, Ambrosia (34.5%, 143/415 tests) and Alternaria alternata (33.5%, 1 762/5 254 tests) in the preschool group, while in the school-age group were Ambrosia (56.4%, 282/500 tests) and Artemisia (48.2%, 573/1 189 tests). The positive rates of egg white, milk, wheat, sesame seed and peanut varied from 2010 to 2020, showing a trend of falling first and then rising(χ²=10.293,χ²=12.066,χ²=7.402,χ²=32.458,χ2=31.747,P<0.05).The positive detection rates of soybean showed a significant downward trend (21.4%, 173/809 tests in 2010, 15.4%, 70/455 tests in 2020, χ²=6.751,P=0.009), while that of shrimp and crab were at a stable low level(χ²=0.263, 1.346;P>0.05). From 2010 to 2020, mold (26.7%, 1 066/3 998 tests in 2010, 40.2% 1 705/4 243 tests in 2020), grass pollen (19.8%, 259/1 308 tests in 2010, 39.3%, 1 472/3 746 tests in 2020), tree pollen(17%, 180/1 058 tests in 2010, 29.8%, 916/3 075 tests in 2020) and animal dander (18.5%, 111/601 tests in 2010, 26.6%, 672/2 522 tests in 2020) were all showed significant upward trend (χ²=168.600, 163.601, 65.931 and 17.271 respectively, P<0.001) but dust mites (30.7%, 1 270/4 132 tests in 2010, 26.7%, 1 126/4 221 tests in 2020) showed a significant downward trend(χ²=16.822,P<0.001).In 2010, the most common inhaled allergen was dust mite 30.7% (1 270/4 132 tests), followed by mold 26.7% (1 066/3 998 tests), while they were mold 40.2% (1 705/1 243 tests), and grass pollen 39.3% (1 472/3 746 texts) respectively in 2020. Conclusion: In the past 11 years, the main food allergens in children were still egg white and milk, wheat, but the mold and pollen gradually replaced dust mite as the most common inhaled allergen.

Role of Vitamin D &amp; Immunoglobulins E in patients of Seasonal Allergic Conjunctivitis

Introduction: Allergic conjunctivitis is in fact a bunch of diseases affecting the visual surface and is usually related with type1 hypersensitivity reactions. Two acute disorders, seasonal allergic conjunctivitis and perennial allergic conjunctivitis, exist, as do 3 chronic illnesses, vernal keratoconjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis. Seasonal allergic conjunctivitis is related with seasonal hypersensitivities that ordinarily happen amid the spring and summer months, and in some cases amid the fall. Exposure to dust, grass and other airborne allergens causes seasonal allergic conjunctivitis. Low levels of vitamin D somewhat related to allergic disorders. This study show a relationship between Serum vitamin D and Immunoglobulin’s E in patients of seasonal allergic conjunctivitis Objective: To evaluate serum vitamin D and serum total immunoglobulin E levels in patients with seasonal allergic conjunctivitis (SAC). Material and Methods Study design: quantitative cross sectional Duration: Six months i.e. 1st September 2021 to 28th February 2022 Data Collection procedure: A cross sectional study was conducted on 100 patients. The study was conducted in Holy Family Hospital Rawalpindi. Ethical approval was taken from ethical committee. An educated consent was taken from the participants. 60 patients in this study presented with seasonal allergic conjunctivitis and 40 healthy normal persons were included. Serum vitamin D and serum total IgE levels were calculated. Results: The average age of the participant in this study was in between 30-50 years of age. In SAC group 40 were males and 20 females. Group two healthy normal consist of 25 males and 15 females. There is a significant decrease of vitamin D level in patients who were diagnosed seasonal allergic conjunctivitis and IgE levels were high when compared to normal healthy group Conclusion: In conclusion, we demonstrated lower plasma vitamin D levels in patients with SAC compared with the control bunch. To conclude a certain association between vitamin D status and allergic conjunctivitis, both multicenter larger case arrangement and further studies examining the impacts of vitamin D supplementation ought to be performed in the long run. Keywords: Vitamin D, seasonal allergic conjunctivitis, IgE, Allergy

THE DIAGNOSTIC VALUE OF ALLERGIC INFLAMMATION MARKERS IN INFANTS WITH BRONCHIOLITIS

Introduction. It is quite important to study the markers of allergic inflammation depending on the status of vitamin D in order to understand the pathogenetic links of bronchiolitis in infants.Aim of study. Analysis of the relationship between serum vitamin D levels and indicators of allergic inflammation (eosinophil cationic protein (ECP) and IgE) in infants with bronchiolitis.Materials and methods. A clinical examination of 55 infants was conducted. The main group consisted of 25 children with bronchiolitis who had a history of allergies. The comparison group consisted of 20 children with bronchiolitis without a burdensome allergy history. The control group included 10 relatively healthy children. The mean age of children in the main group was 7.2 ± 1.4 months, 6.4 ± 1.2 months in the comparison group, and 9.2 ± 1.6 months in the control group.Results of the study. It was found that the duration of hospital stay in children of the main group was 8.2 ± 1.32 days, while in children of the comparison group the duration of stay in hospital was significantly shorter (p &lt;0.05). We found a significant difference in the indicators of allergic inflammation that depended on the status of vitamin D in the examined children. Thus, in children with vitamin D deficiency and insufficiency, a marked increase in ECP (56.3 ± 12.8 ng / ml) and total IgE levels to 127.5 ± 3.12 IU / ml was found compared to the same indicators as in children of the main group with the optimal level of 25 (OH) D, and in children of the comparison group, p˂0,001. It should be noted that the rate of allergic inflammation marker ECP in children of the comparison group with deficiency and insufficiency of vitamin D in serum also had a significant difference when compared with infants of the control group, p˂0.05. Conclusions. In children with bronchiolitis, obtained history of allergies and insufficient levels of vitamin D and its insufficiency, the severity of the disease is manifested by a longer duration of clinical symptoms and hospital stay. Eosinophilic cationic protein can be considered as a marker of allergic inflammation in infants with bronchiolitis.

Cross-Reacting Carbohydrate Determinants Inhibitor Can Improve the Diagnostic Accuracy in Pollen and Food Allergy.

BackgroundCross-reacting carbohydrate determinants (CCD) exist in some pollen and food allergens, but they do not contribute to allergic symptoms. However, CCD can induce specific IgE (sIgE) production and may lead to incorrect allergen diagnosis and treatment. CCD inhibitor is a specific antibody adsorbent which can preclude CCD from binding to sIgE. Currently, the data of CCD inhibition in allergen sIgE test are limited.MethodsThe allergic patients with positive skin prick reactions to two or more pollen and/or food allergen extracts were included in our study. Their sera were obtained and sIgE was tested with an allergen panel that included 29 single and mixed allergens (MEDIWISS Analytic GmbH, China) before and after CCD inhibition. The changes of sIgE against these allergens and the correlations of sIgEs to clinical symptoms were analyzed.ResultsA total of 44 patients were included and 36 (81.82%) of those were multi-sensitized to house dust mites and pollen allergens based on skin prick tests. The sIgE levels and positive rates against most pollen and food allergens were significantly lower after CCD inhibition. The sIgE levels of pollen were positively correlated to those of food allergens before CCD inhibition. However, these correlations were weakened or no longer existed after CCD inhibition. The sIgE against pollen and food allergens showed significantly higher consistency with clinical symptoms after CCD inhibition.ConclusionCross-sensitization caused by CCD is widespread in pollen and food. CCD inhibition test can improve the diagnostic accuracy of pollen and food allergy.

Major Grass Pollen Allergen Components and Cross-Reactive Carbohydrate Determinants in Mugwort-Sensitized Child Patients With Allergic Respiratory Disease in Western China.

Mugwort is a common pollen allergen in western China, and this study aimed to investigate the patterns of molecular sensitization to major grass pollen allergens (mugwort, ragweed, bermuda grass, and timothy grass) and cross-reactive carbohydrate determinants (CCD) in children who were sensitized to mugwort in western China. Serum-specific IgE (sIgE) of major allergen components and CCD were detected among 121 mugwort SPT-positive children via the EUROBlotMaster system if the mugwort-sIgE was positive (MSP). A CCD inhibition test was further performed on the serum of patients with positive CCD-sIgE. Latent class analysis was used to identify the patterns of potential sensitization to major grass pollen allergens. Of a total of 100 patients with mugwort-sIgE positive (MSP), 52.0, 41.0, and 31.0% of them were positive to Art v 1, Art v 3, and Art v 4, respectively. An optimal model with three latent classes was determined using grass pollen allergens, components, and CCD. The sensitization patterns can be summarized as (1) MSP and cosensitized to ragweed, bermuda grass, and timothy grass (23.74%); (2) MSP and cosensitized to Art v 1 (54.08%); (3) MSP and cosensitized to Art v 4, Cyn d 12, Phl p 12 (22.18%). Additionally, CCD sIgE levels had a significant positive correlation with ragweed, bermuda grass, and timothy grass (P < 0.05), and CCD-Inhibitor can highly inhibit the above allergens sIgE. Our findings suggest that Art v 4 was the typical cross-reaction component of mugwort, which is cosensitized to Phl p 12 and Cyn d 12. A wide cross-reaction among ragweed, bermuda grass, and timothy grass caused by CCD was observed.

Blocking function of allergen-specific immunoglobulin G, F(ab')2, and Fab antibodies prepared from patients undergoing Dermatophagoides pteronyssinus immunotherapy

BackgroundThe blocking function of allergen-specific F(ab')2 [sF(ab')2] and Fab (sFab) fragment antibodies prepared from allergen immunotherapy–induced specific immunoglobulin G (sIgG) has not been fully investigated. ObjectiveTo investigate the inhibitory function of sIgG, sF(ab')2, and sFab antibodies in patients undergoing Dermatophagoides pteronyssinus (Der-p) subcutaneous immunotherapy (SCIT). MethodsThis study involved 10 subjects (aged 18-42 years) with house dust mite allergic rhinitis or asthma who received a 156-week course of Der-p SCIT. Total IgG levels were purified from the serum of the participants at weeks 0 and 156 by protein A affinity chromatography. Der-p sIgG was purified by affinity chromatography with Der-p as a ligand at week 156. The sF(ab')2 and sFab antibodies were prepared from Der-p sIgG by treatment with pepsin and papain, respectively. Furthermore, IgE-facilitated allergen binding assay, basophil activation inhibition test, and cytokine release inhibition assay were used to assess the inhibitory function of Der-p sIgG, sF(ab')2, and sFab antibodies. ResultsWe found that the Der-p sIgG, sF(ab')2, and sFab antibodies markedly blocked Der-p–allergen sIgE complex binding to B cells, inhibited basophil activation, and markedly reduced the production of interleukin (IL)-5, IL-13, IL-17, and tumor necrosis factor-α by peripheral blood mononuclear cells. ConclusionSCIT-induced Der-p sIgG, sF(ab')2, and sFab antibodies may block the formation of Der-p–sIgE complexes and may serve as a potential allergen-targeted biologics candidate for the treatment of allergic asthma. Clinical Trial RegistrationThis study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University and registered in the Chinese Clinical Trial Registry (ChiCTR-OOC-15006207, https://www.chictr.org.cn/enindex.aspx).