Inmunoterapia con ácaros Valergen por vía sublingual y subcutánea en pacientes alérgicos. Cabaiguán 2010-2019 / Sublingual and subcutaneous Valergen mite immunotherapy in allergic patients in Cabaiguán 2010-2019

RESUMEN Fundamento: La inmunoterapia consiste en la administración de dosis crecientes del alérgeno para controlar la sensibilidad hacia este. Objetivo: Describir el comportamiento de la inmunoterapia por vía subcutánea o sublingual a ácaros. Metodología: Estudio retrospectivo realizado en Cabaiguán, periodo de 2010 a 2019, el universo de 267 pacientes con pruebas positivas a ácaros y la muestra de 53 pacientes. Los datos se obtuvieron del registro de datos. Resultados: Usó la vía sublingual el 60.4 %, predominó el grupo de edad entre 5-18 años (41.5 %), la vía subcutánea se utilizó en un 39.6 %, fue más frecuente en el sexo masculino (58.5 %). La vía subcutánea se indicó mayoritariamente en la rinitis alérgica (20.7 %) y la sublingual en el asma (32.1 %); para ambas, fue el Dermatofagoide pteronyssinus el ácaro de mayor sensibilidad y utilización (43.4 %), el tiempo de administración dominante fue de 3 años (67.9 %). El control de los síntomas se alcanzó con la vía sublingual (37.7 %). En la vía sublingual no se presentaron eventos adversos en el 43.3 %, con la vía subcutánea 11.3 % de los eventos adversos fueron locales y 7.6 % sistémicos leves. Conclusiones: La vía sublingual fue la más utilizada, la de mayor control de los síntomas y menos eventos adversos en el estudio.

ABSTRACT Background: Immunotherapy consists of the administration of the allergen increasing doses to control sensitivity towards it. Objective: To describe the behavior of subcutaneous or sublingual immunotherapy to mites. Methodology: Retrospective study carried out in Cabaiguán, from 2010 to 2019, the universe of 267 patients with positive tests to mites and the sample 53 patients. Data were obtained from the data record. Results: 60.4 % used sublingual, the age group between 5-18 years prevailed (41.5 %), the subcutaneous was used in 39.6 %, and it was more frequent in males (58.5 %). The subcutaneous was indicated mainly in allergic rhinitis (20.7 %) and sublingual in asthma (32.1 %); for both, Dermatofagoide pteronyssinus was the highest sensitivity and use mite (43.4 %) the dominant administration time was 3 years (67.9 %). Symptom control was achieved by sublingual (37.7 %). In sublingual, there were no adverse events in 43.3 %, with the subcutaneous, 11.3 % of the adverse events were local and 7.6 % were mild systemic. Conclusions: Sublingual was the most used, the one with the highest control of symptoms and the fewest adverse events in the study.

IgY antialérgenos específicos del grupo 1 de ácaros del polvo doméstico inducidos por oligopéptidos sintéticos no glicosilados / Specific IgY anti-group 1 dust mite allergens induced by unglycosylated synthetic oligopeptides

Resumen Introducción. La obtención de anticuerpos específicos capaces de detectar alérgenos del grupo 1 de ácaros del polvo doméstico representa una estrategia potencial de salud pública para reducir la exposición y la sintomatología clínica asociada con el asma y la rinitis alérgica. Objetivo. Producir y purificar anticuerpos aviares antialérgenos específicos del grupo 1 de los ácaros Dermatophagoides sp.y Blomia tropicalis utilizando la tecnología IgY. Materiales y métodos. Se diseñaron y sintetizaron oligopéptidos que evidenciaran epítopes inmunogénicos de los alérgenos Der p1, Der f1 y Blo t1 empleados posteriormente para producir anticuerpos IgY policlonales en gallinas Hy Line Brown. Las IgY presentes en las yemas de los huevos se purificaron mediante cromatografía tiofílica. Su inmunorreactividad y especificidad se determinaron mediante un inmunoensayo ELISA indirecto y Dot Blot. Resultados. Se obtuvo una reactividad elevada de las IgY contra epítopes de alérgenos presentes en extractos de cuerpo entero de D. farinae, D. pteronyssinus y B. tropicalis. Los niveles más altos de IgY se produjeron entre los días 32 y 40 de inmunización. Los anticuerpos mostraron mayor inmunorreactividad y especificidad en el reconocimiento de proteínas de D. farinae, con un límite de detección mayor de 0,03 µg de proteína total delcaroajo las condiciones experimentales analizadas. Las IgY purificadas no mostraron reactividad significativa frente al extracto de Periplaneta americana. Conclusión. La tecnología IgY permitió la producción de anticuerpos específicos contra alérgenos del grupo 1 de los ácaros del polvo al utilizar oligopéptidos sintéticos no glicosilados. Hasta donde se sabe, esta es la primera vez que se usan estos reactivos inmunológicos para la detección de ácaros de importancia médica.

Abstract Introduction: The use of specific antibodies capable of detecting allergens of the group 1 of house dust mites represents a potential strategy to reduce exposure and clinical symptomatology associated with asthma and allergic rhinitis. Objective: To produce and purify chicken antibodies specific for the dust mites Dermatophagoides sp. and B. tropicalis using the IgY technology. Materials and methods: We designed and synthesized oligopeptides showing immunogenic epitopes of Der p1, Der f1, and Blo t1. These were used to produce IgY antibodies in Hy Line Brown chickens. IgY were extracted from egg yolk using thiophilic chromatography. The immunogenicity and specificity were assayed by indirect ELISA and Dot Blot. Results: We obtained high reactivity of IgY antibodies against epitopes of allergens present in whole body mites extracts of D. farinae, D. pteronyssinus, and B. tropicalis. The highest IgY levels were registered between days 32 and 40 after immunization. The antibodies showed high immunoreactivity and specificity towards D. farinae proteins with detection limits above 0.03 µg of mite proteins under the experimental conditions used. Purified IgY did not show significant reactivity when binding to Periplaneta americana extract. Conclusion: The IgY technology allowed the production of specific antibodies against house dust mites group 1 allergens using non-glycosylated synthetic peptides. To our knowledge, this is the first time that this immunochemicals are used in the detection of mites of medical relevance.

Efficacy of dermatophagoides farinae drops in treatment of children with allergic rhinitis and its influence on serum IL-4 and IL-35 levels / 重庆医学

Objective To explore the efficacy of dermatophagoides farinae drops for treating allergic rhinitis in children and its influence on serum IL‐4 and IL‐35 levels .Methods A total of 80 children with mite sensitized allergic rhinitis in the Central Hospital of Nanyang city from January 2012 to October 2013 were selected as the research subjects and randomly divided into the control group and the observation group according to random number table method ,40 cases in each group .The control group was given the symptomatic treatment ,while the observation group was given sublingual dermatophagoides farinae drops .The treatment lasted for 18 months .The efficacy ,symptom score and eosinophil count value (Eos) were observed .ELISA was used to detect ser‐um IL‐4 ,IL‐35 levels .Results The total effective rate after treatment in the observation group was 97 .50% ,which was higher than 92 .50% in the control group ,but without statistically significant difference between them(χ2 =1 .052 6 ,P=0 .305) .After treat‐ment ,the symptom scores ,medication scores and Eos count had statistical differences in the two groups were significantly lower than before(P<0 .05) ,but which had statistical differences between the two groups after treatment(P<0 .05);serum IL‐4 level af‐ter treatment in the two groups were significantly lower than before(P<0 .05) ,while the IL‐35 level was significantly higher than before(P<0 .05) ,the serum IL‐4 and IL‐35 levels after treatment had statistically significant differences between the two groups (P<0 .05) .The incidence rate of adverse reactions showed no statistically significant difference between the two groups (χ2 =0 .213 3 ,P=0 .644) .Conclusion Sublingual specific immunotherapy of dermatophagoides farinae drops can effectively improve the symptoms of mite sensitized allergic rhinitis in children ,reduces proinflammatory cytokine IL‐4 level and increases suppressing in‐flammatory cytokine IL‐35 level .

Der p 1, Der p 2 and Der p 10 IgE Reactivities in Allergic Rhinitis Patients in Korea

BACKGROUND AND OBJECTIVES: To evaluate IgE reactivity profiles to Der p 1, Der p 2, and Der p 10 in house dust mite (HDM) allergic rhinitis (AR) patients in Korea. Symptomatic and serologic changes after sublingual immunotherapy (SLIT) were analyzed according to IgE profiles. MATERIALS AND METHODS: Sixty AR patients diagnosed with an HDM allergy were tested for the presence of IgE antibodies against purified HDM allergen molecules (i.e., nDer p 1, rDer p 2, and rDer p 10) and native Dermatophagoides pteronyssinus (Dp) using ImmunoCAP 250®. Symptom scores and laboratory findings were analyzed after SLIT. RESULTS: Prevalence rates of IgE for Dp, Der p 1, Der p 2, and Der p 10 were 100%, 98.3%, 93.3%, and 8.3%, respectively. After one year of immunotherapy with SLITone○R (standardized to major allergens, but not Der p 10), symptom scores and laboratory findings improved in patients with and without Der p 10 IgE antibodies. CONCLUSION: In Korean AR patients, specific IgE antibodies to Der p 1 or Der p 2 are present in most Dp-allergic patients, while reactivity to Der p 10 is very low. Allergic symptoms improved in patients with Der p 10 IgE antibodies after SLIT.

No Concentration Decrease of House Dust Mite Allergens With Rising Altitude in Alpine Regions

PURPOSE: Several studies over the past 4 decades have indicated a significant reduction in house dust mite (HDM) and HDM allergen concentration in areas higher than 1,500 m above sea level. These have served as basis of allergen avoidance therapies for HDM allergy and asthma. However, modern construction techniques used in the insulation, heating, and glazing of buildings as well as global warming have changed the environmental parameters for HDM living conditions. The present study revisits the paradigm of decreasing HDM allergen concentrations with increasing altitude in the alpine region of Germany and Austria. METHODS: A total of 122 dust samples from different abodes (hotels, privates and mountain huts) at different altitudes (400-2,600 m) were taken, and concentrations of HDM allergens were analyzed. Humidity and temperature conditions, and numerous indoor environmental parameters such as fine dust, type of flooring, age of building, and frequency of cleaning were determined. RESULTS: HDM allergen concentrations did not significantly change with increasing altitude or relative humidity. At the level of indoor parameters, correlations could be found for different flooring types and the concentration of HDM allergens. CONCLUSIONS: In contrast to the widespread view of the relationship between altitude and HDM allergen concentrations, clinically relevant concentrations of HDM allergens could be detected in high-lying alpine regions in Austria and Germany. These results indicate that improvement in conditions of asthmatic patients sensitized against HDMs during a stay at high altitude can no longer be ascribed to decreased levels of HDM allergens, instead, other mechanisms may trigger the beneficial effect.

Sensitization by subcutaneous route is superior to intraperitoneal route in induction of asthma by house dust mite in a murine mode / Sensibilização por via subcutânea é superior à intraperitoneal na indução de asma por ácaro em modelo murino

ABSTRACT Objective To develop a new experimental model of chronic allergic pulmonary disease induced by house dust mite, with marked production of specific immunoglobulin E (IgE), eosinophilic inflammatory infiltrate in the airways and remodeling, comparing two different routes of sensitization. Methods The protocol lasted 30 days. BALB/c mice were divided into six groups and were sensitized subcutaneously or intraperitoneally with saline (negative control), Dermatophagoides pteronyssinus (Der p) 50 or 500mcg in three injections. Subsequently they underwent intranasal challenge with Der p or saline for 7 days and were sacrificed 24 hours after the last challenge. We evaluated the titration of specific IgE anti-Der p, eosinophilic density in peribronchovascular space and airway remodeling. Results Both animals sensitized intraperitoneally and subcutaneously produced specific IgE anti-Der p. Peribronchovascular eosinophilia increased only in mice receiving lower doses of Der p. However, only the group sensitized with Der p 50mcg through subcutaneously route showed significant airway remodeling. Conclusion In this murine model of asthma, both pathways of sensitization led to the production of specific IgE and eosinophilia in the airways. However, only the subcutaneously route was able to induce remodeling. Furthermore, lower doses of Der p used in sensitization were better than higher ones, suggesting immune tolerance. Further studies are required to evaluate the efficacy of this model in the development of bronchial hyperresponsiveness, but it can already be replicated in experiments to create new therapeutic drugs or immunotherapeutic strategies.

RESUMO Objetivo Desenvolver um novo modelo experimental de doença pulmonar alérgica crônica por ácaro, com proeminente produção de imunoglobulina E (IgE) específica, infiltrado inflamatório eosinofílico nas vias aéreas e remodelamento, comparando duas vias diferentes de sensibilização. Métodos O protocolo teve duração de 30 dias. Camundongos BALB/c foram divididos em seis grupos submetidos à sensibilização por via subcutânea ou intraperitoneal com solução salina (controles negativos),Dermatophagoides pteronyssinus (Der p) 50 ou 500mcg, em três aplicações. Posteriormente, foram submetidos à provocação intranasal com Der p ou salina por 7 dias e sacrificados 24 horas após o último desafio. Avaliamos a titulação de IgE específica anti-Der p, densidade eosinofílica no espaço peribroncovascular e remodelamento das vias aéreas. Resultados Tanto os animais sensibilizados por via subcutânea como intraperitoneal produziram IgE específica anti-Der p. Ocorreu aumento da eosinofilia peribroncovascular apenas nos animais que receberam menor dose de Der p. Porém apenas o grupo sensibilizado com Der p 50mcg subcutânea apresentou remodelamento significativo das vias aéreas. Conclusão Neste modelo murino de asma, as duas vias de sensibilização levaram à produção de IgE específica e eosinofilia nas vias aéreas. No entanto, apenas a via subcutânea foi capaz de induzir ao remodelamento. Além disso, doses menores de Der p utilizadas foram superiores às mais elevadas, sugerindo tolerância. Mais estudos são necessários para avaliar a eficácia deste modelo no desenvolvimento da hiperresponsividade brônquica, mas ele pode ser replicado em experimentos para criação de novas estratégias terapêuticas medicamentosas ou imunoterápicas.

Clinical manifestation and sensitization of allergic children from Malaysia

BACKGROUND: An epidemiological rise of allergic diseases in developing countries raises new challenges. Currently a paucity of data exists describing allergy symptomology and sensitization to common food and aeroallergens in young children from developing countries. OBJECTIVE: To compare changes in symptomology, food allergen sensitization and aeroallergen sensitization in a cross-sectional study of children 0.35 kU/L) to common food (egg white, cow's milk, cod fish, wheat, peanut, soya, peanut, and shrimp) and house dust mites (Dermatophagoides pteronyssinus and Blomia tropicalis). RESULTS: In children < 2 years, atopic dermatitis (65.7%) was the most common symptom whereas in children 2-10 years it was rhinoconjunctivitis (74.5%). Higher sensitization rate to eggs (p < 0.01) and cow's milk (p = 0.044) was seen in < 2 years group when compared to the 2-10 years group, but no significant differences for shrimp (p = 0.29), wheat (p = 0.23) and soya (p = 0.057). Interestingly, sensitization to peanut (p = 0.012) and fish (p = 0.035) was significantly decreased in the 2-10 years group. Sensitization to house dust mites (p < 0.01) dramatically increased in the older children. CONCLUSION: Our study supports concept of atopic march from a developing country like Malaysia.

Establishment and functional analysis of a cell model expressing the C-type lectin receptor Langerin / 中华皮肤科杂志

Objective To establish a cell model expressing the Langerhans cell-specific C type lectin receptor Langerin in vitro.Methods The cDNA of Langerin was obtained by PCR and cloned into a eukauotic green fluorescent protein (EGFP) expression vector pEGFP-C 1 with EGFP located in the N terminal region of the Langerin gene.Then,the recombinant plasmid was transfected into a human embryonic kidney carcinoma cell line HEK293T.Subsequently,laser confocal microscopy was performed to observe the expression of EGFP-Langerin fusion protein,and flow cytometry to measure the expression of Langerin.Laser confocal microscopy was also conducted to visualize the recognition and endocytosis of dust mite antigen (nDer p 2) by Langerin.Results PCR and Western blot confirmed the successful transfection of HEK293T cells with the recombinant plasmid as well as the expression of Langerin in the transfected cells.As flow cytometry revealed,the expression level of Langerin in transfected HEK293T cells was increased by 43％ compared with untransfected cells.Laser confocal microscopy showed that green fluorescein-labeled Langerin was successfully expressed,and could bind to and endocytose the red fluorescein-labeled antigen nDer p 2.Conclusions The fusion protein EGFP-Langerin expressed in HEK293T cells showed the distribution characteristic of cell surface receptors,and could bind to and endocytose allergens.

Treatment of Patients with Refractory Atopic Dermatitis Sensitized to House Dust Mites by Using Sublingual Allergen Immunotherapy

Even though atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, its treatment remains a challenge in clinical practice, with most approaches limited to symptomatic, unspecific anti-inflammatory, or immunosuppressive treatments. Many studies have shown AD to have multiple causes that activate complex immunological and inflammatory pathways. However, aeroallergens, and especially the house dust mite (HDM), play a relevant role in the elicitation or exacerbation of eczematous lesions in many AD patients. Accordingly, allergen-specific immunotherapy has been used in AD patients with the aim of redirecting inappropriate immune responses. Here, we report three cases of refractory AD sensitized to HDM who were treated with sublingual immunotherapy.

Dust mite allergy may be a risk factor for early-onset and severe type of alopecia areata / 中华皮肤科杂志

Objective To analyze the clinical features of,concurrence of allergic diseases in,as well as serum levels of total immunoglobulin E (IgE) and specific IgEs in,232 patients with alopecia areata (AA),and to estimate their relationship.Methods Serum samples were obtained from 232 patients with AA and 110 healthy controls from a health check-up center.Turbidimetric immunoassay and fluorescence-based enzyme-linked immunosorbent assay were performed to measure total IgE and specific IgEs to common antigens in these serum samples,respectively.Statistical analysis was carried out by t test,rank sum test,and chi-square test.Results The patients showed a male/female ratio of 127 ∶ 105 with an average age of (26.4 ± 13.8) years and clinical course of (25.3 ± 42.3) months.Among these patients,89 (38.4％) suffered from severe AA,and 67 (28.9％) reported at least one allergic disease.No significant difference was found in the positive rates of serum total IgE (30.2％ vs.21.8％,P ＞ 0.05),anti-Dermatophagoides pteronyssinus and-Cockroach specific IgEs or the serum levels of antiDermatophagoides pteronyssinus or-Cockroach IgE between the patients and healthy controls.The three most common specific IgEs were anti-Dermatophagoides pteronyssinus IgE (34.1％),anti-Dermatophagoides farinae IgE (31.9％) and anti-Cockroach IgE (22.5％) in patients with AA,whose serum levels were positively correlated with the level of serum total IgE separately.A significant increase was observed in the positive rates and serum levels of anti-Dermatophagoides pteronyssinus and-Cockroach specific IgEs in patients with severe and diffuse AA compared with the healthy controls and patients with mild AA,as well as in those of anti-Dermatophagoides pteronyssinus specific IgE in child patients with AA compared with the healthy controls and adult patients with AA (P ＜ 0.05 or 0.01).Conclusions Dust mite allergy may be not only a pathogenic factor for severe,diffuse and childhood AA,but also a risk factor for early onset and severe type of AA.

Safety of Accelerated Schedules of Subcutaneous Allergen Immunotherapy with House Dust Mite Extract in Patients with Atopic Dermatitis

The safety of accelerated schedules of allergen immunotherapy (ASAI) in patients with bronchial asthma (BA) has been reported but there are little data on the safety of ASAI for patients with atopic dermatitis (AD). In this study, we investigated the safety of ASAI in patients with AD. Sixty patients with AD and 18 patients with BA sensitized to house dust mites (HDM) were studied. A maximum maintenance dose of HDM extract, adsorbed to aluminum hydroxide, was administered to patients by subcutaneous injection with either a 3-day protocol (rush immunotherapy) or 1-day protocol (ultra-rush immunotherapy). Systemic reactions were observed 4 of 15 patients (26.7%) with AD during rush immunotherapy, 13 of 45 patients (28.9%) with AD during ultra-rush immunotherapy, and 4 of 18 patients (22.2%) with BA during rush immunotherapy (P > 0.05). No severe or near fatal systemic reactions occurred in 78 subjects of this study. Systemic reactions developed within 4 hr after administration of the maximum allergen dose in 20 of 21 patients (95.2%) with AD and BA who showed systemic reactions during rush or ultra-rush immunotherapy. In conclusion, ASAI was safe and well tolerated in patients with AD. ASAI can be a useful therapeutic option for AD.

House Dust Mite Induces Expression of Intercellular Adhesion Molecule-1 in EoL-1 Human Eosinophilic Leukemic Cells

The house dust mite (HDM) is considered to be the most common indoor allergen associated with bronchial asthma. In this study, we investigated whether crude extract of the HDM Dermatophagoides farinae could activate human eosinophilic leukemic cells (EoL-1) to induce upregulation of cell-surface adhesion molecules. When EoL-1 cells were incubated with D. farinae extract, expression of intercellular adhesion molecule-1 (ICAM-1) significantly increased on the cell surfaces compared to cells incubated with medium alone. In contrast, surface expression of CD11b and CD49d in EoL-1 cells was not affected by D. farinae extract. In addition, pretreatment of cells with NF- kappaB inhibitor (MG-132) or JNK inhibitor (SP600125) significantly inhibited ICAM-1 expression promoted by HDM extract. However, neither p38 MAP kinase inhibitor nor MEK inhibitor prevented HDM-induced ICAM-1 expression in EoL-1 cells. These results suggest that crude extract of D. farinae induces ICAM-1 expression in EoL-1 cells through signaling pathways involving both NF- kappaB and JNK.

Association between skin prick test of dust mites and serum specific IgE / 中国耳鼻咽喉头颈外科

OBJECTIVE To evaluate the association between the results of skin prick test (SPT) of dust mites and serum specific IgE (S-IgE). METHODS A total of 170 patients with allergic rhinitis received SPT and detection of S-IgE of Der p and Der f. The positive rates and grades of S-IgE to different diameters of skin reaction or skin index (SI) were compared. RESULTS The positive rates and grades of S-IgE showed significant differences among different diameters of skin reaction or skin index (SI) patients. The positive rates and grades of S-IgE increased significantly according to the diameters of skin reaction or SI. CONCLUSION There is a significant association between SPT of dust mites and S-IgE.

The relationship between skin test responsiveness and IgE in allergic rhinitis patients sensitive to Dermataphagoides pteronyssinus / 中国耳鼻咽喉头颈外科

0.05). The total serum IgE lev-els in allergic rhinitis patients were compared with those of the controls. The total serum IgE levels of the pa-tients were much higher than those of the controls (geometric mean of the patients and the controls were 224 IU/ml and 50 IU/ml respectively,P