Targeting the RhoA-GEF-H1 pathway of mast cells attenuates experimental airway allergy.

Mast cells are the major effector cells in allergic diseases. RhoA and its downstream pathway is associated with the pathogenesis of airway allergy. The objective of this study is to test a hypothesis that modulating the RhoA-GEF-H1 axis in mast cells can attenuate airway allergy. An airway allergic disorder (AAD) mouse model was employed. Mast cells were isolated from AAD mouse airway tissues to be analyzed by RNA sequencing. We observed that mast cells isolated from the respiratory tract of AAD mice were resistant to apoptosis. Mast cell mediator levels in nasal lavage fluid were correlated with apoptosis resistance in AAD mice. Activation of RhoA in AAD mast cells was related to resistance to apoptosis. Mast cells isolated from the airway tissues in AAD mouse exhibited strong RhoA-GEF-H1 expression. The RhoA-GEF-H1 axis was associated with the lower FasL expression in AAD mast cells. Activation of the RhoA-GEF-H1 axis promoted the production of mediators in mast cells. Inhibition of GEF-H1 facilitated the SIT-induced mast cell apoptosis and enhanced the therapeutic efficacy of AAD. In conclusion, RhoA-GEF-H1 activities are associated with resistance to apoptosis in mast cells isolated from sites of allergic lesions. The state of apoptosis resistance in mast cells is associated with the state of AAD disease. Inhibition of GEF-H1 restores the sensitivity of mast cells to apoptosis inducers, and alleviates experimental AAD in mice.

Intranasal administration of nucleus-deliverable GATA3-TMD alleviates the symptoms of allergic asthma.

Although the T helper 2 (Th2) subset is a critical player in the humoral immune response to extracellular parasites and suppression of Th1-mediated inflammation, Th2 cells have been implicated in allergic inflammatory diseases such as asthma, allergic rhinitis, and atopic dermatitis. GATA binding protein 3 (GATA3) is a primary transcription factor that mediates Th2 differentiation and secretion of Th2 cytokines, including IL-4, IL-5, and IL-13. Here, a nucleus-deliverable form of GATA3-transcription modulation domain (TMD) (ndG3-TMD) was generated using Hph-1 human protein transduction domain (PTD) to modulate the transcriptional function of endogenous GATA3 without genetic manipulation. ndG3-TMD was shown to be efficiently delivered into the cell nucleus quickly without affecting cell viability or intracellular signaling events for T cell activation. ndG3-TMD exhibited a specific inhibitory function for the endogenous GATA3-mediated transcription, such as Th2 cell differentiation and Th2-type cytokine production. Intranasal administration of ndG3-TMD significantly alleviated airway hyperresponsiveness, infiltration of immune cells, and serum IgE level in an OVA-induced mouse model of asthma. Also, Th2 cytokine secretion by the splenocytes isolated from the ndG3-TMD-treated mice substantially decreased. Our results suggest that ndG3-TMD can be a new therapeutic reagent to suppress Th2-mediated allergic diseases through intranasal delivery.

Effects of human adipose tissue- and bone marrow-derived mesenchymal stem cells on airway inflammation and remodeling in a murine model of chronic asthma.

It is challenging to overcome difficult-to-treat asthma, and cell-based therapies are attracting increasing interest. We assessed the effects of mesenchymal stem cell (MSC) treatments using a murine model of chronic ovalbumin (OVA)-challenged asthma. We developed a murine model of chronic allergic asthma using OVA sensitization and challenge. Human adipose-derived MSCs (hADSCs) or human bone marrow-derived MSCs (hBMSCs) were administered. We measured the levels of resistin-like molecule-ß (RELM-ß). We also measured RELM-ß in asthma patients and normal controls. OVA-challenged mice exhibited increased airway hyper-responsiveness, inflammation, and remodeling. hBMSC treatment remarkably decreased airway hyper-responsiveness but hADSC treatment did not. Both MSCs alleviated airway inflammation, but hBMSCs tended to have a more significant effect. hBMSC treatment reduced Th2-cytokine levels but hADSC treatment did not. Both treatments reduced airway remodeling. The RELM-ß level decreased in the OVA-challenged control group, but increased in both treatment groups. We found that the serum level of RELM-ß was lower in asthma patients than controls. MSC treatments alleviated the airway inflammation, hyper-responsiveness, and remodeling associated with chronic asthma. hBMSCs were more effective than hADSCs. The RELM-ß levels increased in both treatment groups; the RELM-ß level may serve as a biomarker of MSC treatment efficacy.

Allergen immunotherapy for respiratory allergies in clinical practice: A comprehensive review.

Allergen-specific immunotherapy (AIT) is the only treatment that modifies the underlying pathophysiology of IgE-mediated allergic diseases. Evidence shows the efficacy in achieving better control of the symptoms and reduction in medication use in patients with allergic rhinoconjunctivitis and/or asthma. It should be used in association with proper pharmacotherapy for at least three years. The benefits are sustained for several years after discontinuation of treatment. Moreover, it may prevent the development of new sensitization and progression of disease from allergic rhinitis to asthma in children. The favorable efficacy of AIT is associate to the appropriate selection of patients, allergen extracts, adherence, and duration of treatment. Safety during AIT is another concerning issue. AIT has an acceptable safety profile if administered under the appropriate circumstances. Future studies investigating the prescription, efficacy, and safety need to be developed. The new application routes, use of adjuvants, modification of allergens, and use of biologics are currently under evaluation. Moreover, there is an urgent need for real-world data in developing countries regarding the cost-effectiveness analysis, and optimization of AIT schedules and products, so that clinical practice and implementation of AIT for respiratory allergic diseases can be effective and safe.

Local Respiratory Allergy: From Rhinitis Phenotype to Disease Spectrum.

Local respiratory allergy (LRA) is defined by the negativity of atopy tests, a clinical history suggestive of airway allergy and a positive response to the nasal and/or bronchial allergen challenge. The clinical spectrum of LRA is comprised of three conditions: local allergic rhinitis (LAR) and local allergic asthma in non-atopic patients, and dual allergic rhinitis (coexistence of allergic rhinitis and LAR) in atopic individuals. LRA is an independent disease phenotype not progressing to atopy over time, but naturally evolving to the clinical worsening and the onset of comorbidities. Published data suggests that LRA is mediated through the mucosal synthesis of allergen-specific (s)IgE, which binds to FcϵRI on resident mast cells, and in >50% of cases traffics to the blood stream to sensitize circulating basophils. To date, 4 clinical trials have demonstrated the capacity of allergen immunotherapy (AIT) to decrease nasal, conjunctival and bronchial symptoms, to improve quality of life, to increase the threshold dose of allergen eliciting respiratory symptoms, and to induce serum sIgG4 in LRA individuals. Collectively, these data indicate that local allergy is a relevant disease mechanisms in both atopic and non-atopic patients with airway diseases.

Peptide allergen-specific immunotherapy for allergic airway diseases-State of the art.

Allergen-specific immunotherapy (AIT) is the only means of altering the natural immunological course of allergic diseases and achieving long-term remission. Pharmacological measures are able to suppress the immune response and/or ameliorate the symptoms but there is a risk of relapse soon after these measures are withdrawn. Current AIT approaches depend on the administration of intact allergens, often comprising crude extracts of the allergen. We propose that the challenges arising from current approaches, including the risk of serious side-effects, burdensome duration of treatment, poor compliance and high cost, are overcome by application of peptides based on CD4+ T cell epitopes rather than whole allergens. Here we describe evolving approaches, summarize clinical trials involving peptide AIT in allergic rhinitis and asthma, discuss the putative mechanisms involved in their action, address gaps in evidence and propose future directions for research and clinical development.

TMT-based quantitative proteomics reveals suppression of SLC3A2 and ATP1A3 expression contributes to the inhibitory role of acupuncture on airway inflammation in an OVA-induced mouse asthma model.

Asthma is a chronic airway inflammatory disease and acupuncture is frequently used in patients suffering from asthma in clinic. However, the regulatory mechanism of acupuncture treatment in asthma is not fully elucidated. We sought to investigate the effectiveness of acupuncture on asthma and the associated regulatory mechanism. An ovalbumin (OVA)-induced mouse asthma model was established and the effect of acupuncture on airway hyperresponsiveness (AHR), mucus hypersecretion and inflammation was assessed. Tandem mass tag (TMT)-based quantitative proteomics analysis of lung tissue and bioinformatics analysis were performed. Our results revealed that the OVA-induced mouse asthma model was successfully established with the significantly elevated AHR to methacholine (Mch), and acupuncture was effective in attenuation of AHR to Mch, peribronchial and perivascular inflammation and mucus production. The inflammatory cells around the airways, mucous secretion as well as levels of IgE, CCL5, CCL11, IL-17A in bronchoalveolar lavage fluid (BALF) and IL-4, IL-5 and IL-13 levels in serum were siginificantly inhibited by acupuncture. TMT-based quantitative proteomics analysis found that a total of 6078 quantifiable proteins were identified, and 564 (334 up-regulated and 230 down regulated) differentially expressed proteins (DEPs) were identified in OVA-induced asthma model group (A) versus normal control group (NC). Acupuncture treatment resulted in 667 DEPs (416 up-regulated and 251 down regulated) compared with A group, and 86 overlapping DEPs were identified in NC, A and AA groups. Among the 86 overlapping DEPs, we identified 41 DEPs regulated by acupuncture. Based on the above data, we performed a systematic bioinformatics analysis of the 41 DEPs, and results showed that these 41 DEPs were predominantly related to 4 KEGG pathways including SNARE interactions in vesicular transport, ferroptosis, endocrine and other factor-regulated calcium reabsorption, and protein digestion and absorption. DEPs of SLC3A2 and ATP1A3 expression levels were verified by immumohistochemical staining. Mice in OVA-induced asthma model group had elevated SLC3A2 and ATP1A3 expression and acupuncture had the ability to downregulate SLC3A2 and ATP1A3 protein expression. Furthermore, acupuncture reduced the MDA level and increased the GSH and SOD levels in the lung tissue. Taken together, our data suggested that acupuncture was effective in treating asthma by attenuation of AHR, mucus secretion and airway inflammation, and the mechanism was associated with regulation of ferroptosis, SLC3A2 and ATP1A3 protein expression as well as oxidative stress. Results from our experiments revealed the anti-inflammatory effect of acupuncture in OVA-induced mouse asthma model, leading to a more effective approach to be chosen by patients in clinic.

High dose vitamin D3 empowers effects of subcutaneous immunotherapy in a grass pollen-driven mouse model of asthma.

Allergen-specific immunotherapy (AIT) has the potential to provide long-term protection against allergic diseases. However, efficacy of AIT is suboptimal, while application of high doses allergen has safety concerns. The use of adjuvants, like 1,25(OH)2VitD3 (VitD3), can improve efficacy of AIT. We have previously shown that low dose VitD3 can enhance suppression of airway inflammation, but not airway hyperresponsiveness in a grass pollen (GP)-subcutaneous immunotherapy (SCIT) mouse model of allergic asthma. We here aim to determine the optimal dose and formulation of VitD3 for the GP SCIT. GP-sensitized BALBc/ByJ mice received three SCIT injections of VitD3-GP (30, 100, and 300 ng or placebo). Separately, synthetic lipids, SAINT, was added to the VitD3-GP-SCIT formulation (300 nmol) and control groups. Subsequently, mice were challenged with intranasal GP, and airway hyperresponsiveness, GP-specific IgE, -IgG1, and -IgG2a, ear-swelling responses (ESR), eosinophils in broncho-alveolar lavage fluid and lung were measured. VitD3 supplementation of GP-SCIT dose-dependently induced significantly enhanced suppression of spIgE, inflammation and hyperresponsiveness, while neutralizing capacity was improved and ESR were reduced. Addition of VitD3 further decreased Th2 cytokine responses and innate cytokines to allergens in lung tissue by GP-SCIT. However, addition of synthetic lipids to the allergen/VitD3 mixes had no additional effect on VitD3-GP-SCIT. We find a clear, dose dependent effect of VitD3 on GP-SCIT-mediated suppression of allergic inflammation and airway hyperresponsiveness. In contrast, addition of synthetic lipids to the allergen/VitD3 mix had no therapeutic effect. These studies underscore the relevance of VitD3 as an adjuvant to improve clinical efficacy of SCIT treatment regimens.

Collagenous colitis in a child induced by chronic respiratory allergy: A case report.

INTRODUCTION: Collagen colitis (CC) is a microscopic colitis diagnosed by mucosal biopsy and is extremely rare in children. PATIENT CONCERNS: We reported a child with severe persistent diarrhea that could not be relieved with traditional diarrheal treatment. No abnormalities were found after multiple colonoscopies. DIAGNOSES: A significant increase in total IgE levels was found in the patient's blood. He had a history of mild chronic allergic rhinitis and slightly intermittent wheezing. However, we found that the child had a hyperallergic reaction to multiple respiratory antigens and had mild pulmonary dysfunction. Finally, colonoscopy with biopsy identified the diagnosis of CC. INTERVENTION: Considering that a respiratory allergic reaction was one of the causes of diarrhea, anti-allergic treatment was given to the child, and his severe diarrhea was soon relieved. Corticosteroid treatment was suggested to the patient, but his parents firmly refused steroid therapy. According to the patient's specific allergic reaction to mites, desensitization treatment was finally chosen for him. OUTCOMES: After 1 year of desensitization for dust mites, the patient's respiratory symptoms improved, total IgE levels decreased, autoantibodies declined, and diarrhea did not reoccur. Colonoscopy with biopsy showed a significant improvement in pathology. CONCLUSION: CC in children is rare, and childhood CC induced by a respiratory allergic reaction has not been previously reported. Therefore, this is a special case of CC in a patient who was cured with anti-allergy treatments and desensitization instead of steroid therapy.

Allergen immunotherapy for respiratory allergy: to what extent can the risk of systemic reactions be reduced?

INTRODUCTION: Allergen immunotherapy is an effective treatment for respiratory allergy, but the administration to patients of extracts of the causative allergen may elicit systemic reactions, which include, particularly with subcutaneous immunotherapy (SCIT), anaphylaxis. In the past, the occurrence (tough rare) of fatal reactions has represented a serious problem that has limited the prescription of SCIT. AREAS COVERED: The authors analyzed in this review the safety data of SCIT, especially concerning the years following the identification of uncontrolled asthma at the moment of allergen injection as the major risk of life-threatening reactions and fatalities. The safety of SLIT, which is far better than SCIT, was analyzed and its specific risk factors for systemic reactions were highlighted. EXPERT OPINION: Presently, the safety profile of SCIT and SLIT is satisfactory, provided the treatment is administered by physicians experienced in this treatment, who are aware of the known risk factors for severe reactions and who implement all measures to avoid them. For SLIT, which is self-administered by the patient, receiving the first dose under medical control is recommended.

[The clinical practice of allergen immunotherapy in Mexico according to 277 allergists who were surveyed during a three-year AIT course]. / La práctica clínica de la inmunoterapia con alérgenos en México según 277 alergólogos encuestados durante un curso trianual.

BACKGROUND: There are different guidelines for the diagnosis of allergic diseases and the application of allergen immunotherapy (AIT). OBJECTIVE: To describe how Mexican allergists diagnose and treat respiratory and food allergies with AIT. METHODS: 227 allergists who attended an immunotherapy symposium were surveyed; the topics investigated were the daily practices in the diagnosis of respiratory and food allergies, as well as ways to apply AIT. RESULTS: The surveyed allergists use skin prick tests for the diagnosis of both respiratory and food allergies in 100 % and 87.7 % of their cases respectively; in vitro diagnosis through serum specific IgE in 55.5 % and 63 %, and molecular diagnostics in 14.1% and 13.2 %. For aeroallergens, 81 % prescribe subcutaneous AIT, 77.9 % use liquid sublingual AIT, and 1.8 % prefer SLIT in tablets; however, 45 % indicated that they would use tablets in the future. Regarding food allergens, most respondents did not prescribe AIT; however, 55% of them are interested in oral AIT and 59% of them are interested in sublingual AIT. CONCLUSIONS: Generally, the diagnosis and treatment of allergic diseases are carried out according to international guidelines; besides, the interviewed allergists expressed flexibility to adopt new schemes.

Antecedentes: Existen lineamientos para el diagnóstico de las enfermedades alérgicas y la aplicación de inmunoterapia con alérgenos (ITA). Objetivo: Describir cómo los alergólogos mexicanos diagnostican y tratan con ITA las alergias alimentaria y respiratoria. Métodos: Se encuestó a 227 alergólogos que acudieron a un simposio de inmunoterapia; se indagaron prácticas cotidianas en el diagnóstico de las alergias respiratoria y alimentaria, así como en la forma de aplicar la ITA. Resultados: Los alergólogos utilizan las pruebas cutáneas por punción para el diagnóstico de las alergias respiratorias y alimentarias en 100 y 87.7 % de los casos de una y otra; diagnóstico in vitro mediante determinación de IgE alérgeno-específica en 55.5 y 63 %; y diagnóstico molecular por componentes en 14.1 y 13.2 %. Para los aeroalérgenos, 81 % emplea ITA subcutánea; 77.9 %, ITA sublingual líquida; 1.8 %, ITA sublingual en tabletas; 45 % indicó que estaba dispuesto a emplear tabletas en el futuro. Para los alérgenos de alimentos, la mayoría no utilizaba ITA, aunque 55 % se interesa en la ITA oral y 59 %, en la ITA sublingual. Conclusiones: En términos generales, el diagnóstico y tratamiento de las enfermedades alérgicas se realizan conforme los lineamientos internacionales, además, los alergólogos encuestados mostraron flexibilidad para adoptar nuevos esquemas.

Management of eosinophilic esophagitis in children according to atopic status: A retrospective cohort in northeast of France.

INTRODUCTION: Most children with eosinophilic esophagitis (EoE) are atopic, but the impact of atopy on the remission and development of EoE is still unclear. The aim of our study was to determine the impact of atopy on remission of EoE and to describe allergy tests and the choice of treatment for a cohort of EoE children in France. METHODS: All children diagnosed with EoE between January 2013 and June 2018 in the five pediatric centers in the northeast of France were included. Children were divided into two groups according to personal atopic disorders. Histological remission was defined on the basis of an eosinophilic count below 15 eosinophils per high-power field. RESULTS: Among the 49 children included, 38 (78%) were atopic. Allergy tests were performed for 45 children (92%). Rates of sensitization were similar in both groups: 64% had food sensitization and 64% had aeroallergen sensitization. The most commonly attempted first-line therapy was with proton pump inhibitors (63%), followed by swallowed topical steroids (STS) (18%). First-line therapy was not associated with atopic status (P=0.88). Atopic children had a nonsignificant tendency for a higher remission rate after STS (55% vs. 0%, P=0.24) and a higher global remission rate (54% vs. 33%, P=0.18) compared with non-atopic children. CONCLUSION: Allergy testing is relevant in the majority of children with EoE whether or not they have atopic disorders. Atopy seems to be associated with better response to STS. Further studies are needed to determine whether atopic status determines histological response.

Understanding the immunology of asthma: Pathophysiology, biomarkers, and treatments for asthma endotypes.

Asthma is a common disease in paediatrics and adults with a significant morbidity, mortality, and financial burden worldwide. Asthma is now recognized as a heterogeneous disease and emerging clinical and laboratory research has elucidated understanding of asthma's underlying immunology. The future of asthma is classifying asthma by endotype through connecting discernible characteristics with immunological mechanisms. This comprehensive review of the immunology of asthma details the currently known pathophysiology and clinical practice biomarkers in addition to forefront biologic and targeted therapies for all of the asthma endotypes. By understanding the immunology of asthma, practitioners will be able to diagnose patients by asthma endotype and provide personalized, biomarker-driven treatments to effectively control patients' asthma.

Allergen-specific Immunotherapy for Inhalant Allergens in Children.

Allergen-specific immunotherapy (AIT) for aeroallergens consists of the administration of standardized allergen extracts to patients with respiratory IgE-mediated diseases to the same allergen in order to achieve immune tolerance to the allergen and prevent the onset of symptoms. AIT is usually delivered by sublingual (SLIT), subcutaneous (SCIT) route. AIT with one or multiple allergens currently represents the only causal treatment able to change the natural history of allergic airway diseases. Significant progresses have been made in terms of AIT efficacy and safety. In this paper, mechanisms of action, indication and side effects of allergen immunotherapy are reviewed. SLIT and SCIT have been found to be effective in the treatment of asthma and rhinoconjunctivitis due to inhalant allergens. The route of AIT administration should be selected on availability, cost (dependent from the local health system), tolerability (better for SLIT), patient's preference (injections are less accepted in young children), and adherence (higher for SCIT beyond pediatric age). However, it should be taken into account that metanalyses on AIT do not consider that effectiveness and safety depend upon the product chosen for treatment. Each product should be separately assessed to avoid generalization on administration routes or age group that may affect the decision.

Modulation of protective reflex cough by acute immune driven inflammation of lower airways in anesthetized rabbits.

Chronic irritating cough in patients with allergic disorders may reflect behavioral or reflex response that is inappropriately matched to the stimulus present in the respiratory tract. Such dysregulated response is likely caused by sensory nerve damage driven by allergic mediators leading to cough hypersensitivity. Some indirect findings suggest that even acid-sensitive, capsaicin-insensitive A-δ fibers called "cough receptors" that are likely responsible for protective reflex cough may be modulated through immune driven inflammation. The aim of this study was to find out whether protective reflex cough is altered during acute allergic airway inflammation in rabbits sensitized to ovalbumin. In order to evaluate the effect of such inflammation exclusively on protective reflex cough, C-fiber mediated cough was silenced using general anesthesia. Cough provocation using citric acid inhalation and mechanical stimulation of trachea was realized in 16 ovalbumin (OVA) sensitized, anesthetized and tracheotomised rabbits 24h after OVA (OVA group, n = 9) or saline challenge (control group, n = 7). Number of coughs provoked by citric acid inhalation did not differ between OVA and control group (12,2 ±6,1 vs. 17,9 ± 6,9; p = 0.5). Allergic airway inflammation induced significant modulation of cough threshold (CT) to mechanical stimulus. Mechanically induced cough reflex in OVA group was either up-regulated (subgroup named "responders" CT: 50 msec (50-50); n = 5 p = 0.003) or down-regulated (subgroup named "non responders", CT: 1200 msec (1200-1200); n = 4 p = 0.001) when compared to control group (CT: 150 msec (75-525)). These results advocate that allergen may induce longer lasting changes of reflex cough pathway, leading to its up- or down-regulation. These findings may be of interest as they suggest that effective therapies for chronic cough in allergic patients should target sensitized component of both, reflex and behavioral cough.

Adoptive transfer of type 1 regulatory T cells suppressed the development of airway hyperresponsiveness in ovalbumin-induced airway inflammation model mice.

Type 1 regulatory T (Tr1) cells are CD4+ T cells that produce a large amount of IL-10, an anti-inflammatory cytokine. However, it has not been fully elucidated whether Tr1 cells suppress allergic asthma. In this study, the effects of adoptive transfer of in vitro-induced Tr1 cells on allergic asthma were evaluated. Splenocytes from ovalbumin (OVA)-sensitized BALB/c mice were cultured with OVA, IL-21, IL-27, and TGF-ß. After culture, IL-10-producing CD4+ T cells were isolated by Dynabeads mouse CD4 and IL-10 secretion assay, and analyzed by flow cytometry. Purified Tr1 cells (IL-10+ CD4+ T cells) were intravenously injected into OVA-sensitized BALB/c mice. The recipient mice were intratracheally challenged with OVA. Airway hyperresponsiveness to methacholine was assessed by the forced oscillation technique, followed by bronchoalveolar lavage (BAL). Almost all of the induced IL-10-producing CD4+ T cells were negative for interferon-γ, IL-4, IL-17A, and forkhead box P3, suggesting that the cells were Tr1 cells. The adoptive transfer of Tr1 cells significantly suppressed the development of airway hyperresponsiveness, and increases in IL-5, eosinophils, and neutrophils in BAL fluid. In conclusion, we demonstrated that Tr1 cells suppressed allergic asthma in mice.

[The effectiveness and safety of subcutaneous immunotherapy for inhalable allergens in patients with respiratory allergies]. / Eficacia y seguridad de la inmunoterapia subcutánea para alérgenos inhalables en pacientes con alergia respiratoria.

BACKGROUND: Specific immunotherapy is a treatment aimed at modifying the course of the allergic disease, with which important immunological and clinical changes are achieved. OBJECTIVE: To assess the effectiveness and safety of subcutaneous immunotherapy in patients diagnosed with respiratory allergies in the University Hospital of Puebla, Mexico. METHODS: A longitudinal, analytic, quasi-experimental study. The study was carried out with patients aged four to sixty-five years, diagnosed with allergic rhinitis or asthma, with sensitization to aeroallergens, in whom immunotherapy was started. For the effectiveness assessment, the Control of Allergic Rhinitis and Asthma Test (CARAT) was used. Safety was assessed through Portnoy's Questionnaire Survey of Adverse Reactions. RESULTS: 59 patients were included: 72.9% were female; 23.7% of them were diagnosed with allergic rhinitis and asthma, and 76.3% were diagnosed with allergic rhinitis. The comparison of averages of the CARAT questionnaire at the beginning of the treatment and after four months of follow up showed a statistically significant positive development. An incidence of adverse local reactions of 9.03% was found; no adverse systemic reactions were reported. CONCLUSIONS: The assessed scheme of subcutaneous immunotherapy got to significantly decrease the asthma symptoms and AR symptoms, with a desirable safety profile.

Antecedentes: La inmunoterapia específica es un tratamiento orientado a modificar el curso de la enfermedad alérgica y con la que se han logrado importantes cambios inmunológicos y clínicos. Objetivo: Evaluar eficacia y seguridad de la inmunoterapia subcutánea en pacientes con diagnóstico de alergia respiratoria en el Hospital Universitario de Puebla, México. Métodos: Estudio longitudinal, analítico, cuasiexperimental. Se incluyeron pacientes de cuatro a 65 años con diagnóstico de asma o rinitis alérgica, con sensibilización a aeroalérgenos, que iniciaron tratamiento con inmunoterapia. Para la valoración de la eficacia se utilizó el cuestionario Control of Allergic Rhinitis and Asthma Test (CARAT). La seguridad se evaluó mediante el cuestionario de reacciones adversas de Portnoy. Resultados: Se incluyeron 59 pacientes, 72.9 % fueron mujeres; 23.7 % con diagnóstico de rinitis alérgica y asma y 76.3 % con diagnóstico de rinitis alérgica. La comparación de promedios del cuestionario CARAT al inicio del tratamiento y a los cuatro meses de seguimiento mostró evolución favorable estadísticamente significativa. Se encontró una incidencia de reacciones adversas locales de 9.03 %; no se reportaron reacciones adversas sistémicas. Conclusiones: El esquema de inmunoterapia subcutánea evaluado logra disminuir significativamente los síntomas del asma y la rinitis alérgica, con un conveniente perfil de seguridad.

CRM197-Coupled Der p 2 Peptides Suppress Allergic Airway Inflammation in a Der p 2-Induced Asthma Mouse Model.

Allergic diseases affect more than 25% of the global population. Der p 2 is the major allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus. Allergen-specific immunotherapy is the only treatment to change the course of allergic diseases. In this study, two synthesized Der p 2 peptides coupled to cross-reacting material 197 (CRM197) showed reduced IgE reactivity and allergenic activity. CRM197-coupled Der p 2 peptides induced rDer p 2-specific IgG1 antibodies in mice, which could inhibit HDM-allergic patients' IgE binding to rDer p 2. The immunity effects of CRM197-coupled Der p 2 peptides were studied in an rDer p 2-induced asthma mouse model. CRM197-coupled Der p 2 peptides can suppress asthmatic airway inflammation in this model. Analysis of IL-4, IL-5, and IFN-γ levels in bronchoalveolar lavage fluid revealed that the suppression was associated with a shift from a Th2 to a Th1 response. Thus, CRM197-bound Der p 2 peptides exhibited less allergenic activity than the rDer p 2 allergen, which preserved immunogenicity and may be candidates for mite allergy vaccines.