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1.
Hautarzt ; 72(9): 751-759, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34383107

RESUMO

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


Assuntos
Alérgenos , Hipersensibilidade , Dessensibilização Imunológica , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Imunoglobulina E , Patologia Molecular
2.
Int Arch Allergy Immunol ; 182(9): 777-787, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34289474

RESUMO

BACKGROUND: The efficacy of allergen-specific immunotherapy (AIT) is mainly depended on the tolerogenic immune responses elicited. Properly conjugated nano-vaccine has the advantages of both specific targeting and continuous and on-demand release of allergen. OBJECTIVES: The aim of this study is to investigate the effects of a dendritic cells (DCs)-targeting nano-vaccine for AIT. METHODS: The nano-vaccine was produced by coupling polylactic-co-glycolic acid (PLGA)-encapsulated ovalbumin (OVA) with mannan. Allergen capture, human monocytes-derived DCs (hMoDCs) activation, and T cells responses were assessed by flow cytometry, confocal microscopy, quantitative real-time PCR, ELISA, and Cytometric Bead Array. Balb/c mice were immunized with the nano-vaccines, and the immune responses were analyzed. RESULTS: OVA-PLGA nanoparticle (NP) displayed favorable safety profile. OVA-mannan-PLGA NP was captured more efficiently by hMoDCs than OVA-PLGA NP, which was mediated mainly through DC-specific intercellular adhesion molecule 3-grabbing nonintegrin. A tolerogenic phenotype of hMoDCs was induced by OVA-mannan-PLGA NP, but not OVA-PLGA NP, and increased number of regulatory T (Treg) cells was generated subsequently in in vitro coculture. Immunization of Balb/c mice with OVA-mannan-PLGA NP resulted in lower serum level of OVA-specific immunoglobulins and less production of pro-inflammatory cytokines in splenocytes culture than the mice immunized with OVA-PLAG NP, PLGA NP, or OVA, while the number of splenic Treg cells was higher in OVA-mannan-PLGA group than in other groups. Moreover, preimmunization with OVA-mannan-PLGA NP significantly inhibited the Th2 immune response induced by OVA sensitization. CONCLUSIONS: The biocompatible PLGA-encapsulated OVA coupling with mannan has augmented ability for tolerance induction and could be developed as a novel vaccine for AIT.


Assuntos
Alérgenos/imunologia , Células Dendríticas/imunologia , Mananas/imunologia , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Linfócitos T Reguladores/imunologia , Vacinas/imunologia , Alérgenos/administração & dosagem , Animais , Dessensibilização Imunológica , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Tolerância Imunológica , Imunização , Camundongos , Linfócitos T Reguladores/metabolismo
3.
Medicine (Baltimore) ; 100(27): e26494, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232182

RESUMO

ABSTRACT: This retrospective study aimed to describe the association between the "ß-lactam allergy" labeling (BLAL) and the outcomes of a cohort of intensive care unit (ICU) patients.Retrospective cohort study.Seven ICU of the Aix Marseille University Hospitals from Marseille in France.We collected the uses of the label "ß-lactam allergy" in the electronic medical files of patients aged 18 years or more who required more than 48 hours in the ICU with mechanical ventilation and/or vasopressors admitted to 7 ICUs of a single institution.We retrospectively compared the patients with this labeling (BLAL group) with those without this labeling (control group).The primary outcome was the duration of ICU stay. Among the 7146 patients included in the analysis, 440 and 6706 patients were classified in the BLAL group and the control group, respectively. The prevalence of BLAL was 6.2%. In univariate and multivariate analyses, BLAL was weakly or not associated with the duration of ICU and hospital stays (respectively, 6 [3-14] vs 6 [3-14] days, standardized beta -0.09, P = .046; and 18 [10-29] vs 15 [8-28] days, standardized beta -0.09, P = .344). In multivariate analysis, the ICU and 28-day mortality rates were both lower in the BLAL group than in the control group (aOR 0.79 95% CI [0.64-0.98] P = .032 and 0.79 [0.63-0.99] P = .042). Antibiotic use differed between the 2 groups, but the outcomes were similar in the subgroups of septic patients in the BLAL group and the control group.In our cohort, the labeling of a ß-lactam allergy was not associated with prolonged ICU and hospital stays. An association was found between the labeling of a ß-lactam allergy and lower ICU and 28-day mortality rates.Trial registration: Retrospectively registered.


Assuntos
Cuidados Críticos/métodos , Hipersensibilidade/etiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , beta-Lactamas/efeitos adversos , Feminino , Seguimentos , França/epidemiologia , Mortalidade Hospitalar/tendências , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/terapia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendências
4.
Curr Opin Allergy Clin Immunol ; 21(5): 500-506, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34269742

RESUMO

PURPOSE OF REVIEW: To analyze if recommendations given before and during the COVID-19 pandemic are still a valid option for patients suffering of ocular allergy (OA). RECENT FINDINGS: During the last year many doctors and patients requested suggestions for the treatment of OA patients in COVID-19 time. Most of them were given by phone calls and emails following the recommendations given by Scientific Societies. SUMMARY: Considering the current multiple problems related to the COVID-19 pandemic, OA has not been considered a priority, even though patients need treatments. Topical antiallergic drugs are still the first option to treat all kind of OA, with the addition of topical corticosteroids in the severe forms of vernal and atopic keratoconjunctivitis (VKC and AKC) even in patients at risk of COVID-19. Topical immunomodulation is still recommended in severe forms of VKC and AKC unless the patient is infected. The number of patients treated with these drugs in our Center was similar than previous years. The risk to have a VKC patient affected by COVID-19 is similar to the general pediatric population but with a lower OR. In 2021, still in COVID-time, the management of OA should follow the previous recommendations with an update due to the risk of infection.


Assuntos
COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Conjuntivite Alérgica/terapia , Pandemias , Conjuntivite Alérgica/tratamento farmacológico , Oftalmopatias/terapia , Humanos , Hipersensibilidade/terapia , Guias de Prática Clínica como Assunto
5.
Arch. argent. pediatr ; 119(3): e193-e201, Junio 2021. tab, ilus
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1223310

RESUMO

Se describen como desafíos actuales en mucopolisacaridosis I la necesidad de una clasificación adecuada, vinculándola a las indicaciones terapéuticas; el diagnóstico temprano desde la pesquisa neonatal, sus ventajas y dificultades hasta la sospecha clínica de las formas grave y atenuada; el cuidado de la patología espinal y oftalmológica, desde el diagnóstico, el seguimiento y el tratamiento; las reacciones alérgicas por terapia de reemplazo enzimático, su diagnóstico y tratamiento. Por último, la transición hacia el cuidado adulto


Here we describe the current challenges of mucopolysaccharidosis type I: the need for an adequate classification, establishing its relationship to therapeutic indications; an early diagnosis, from neonatal screening, its advantages and barriers, to clinical suspicion of severe and attenuated forms; spinal and eye disease care, from diagnosis to follow-up and treatment; allergic reactions caused by enzyme replacement therapy, their diagnosis and treatment. And lastly, transition to adult care


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Mucopolissacaridose I/diagnóstico , Mucopolissacaridose I/terapia , Triagem Neonatal , Mucopolissacaridose I/classificação , Oftalmopatias/diagnóstico , Oftalmopatias/terapia , Transição para Assistência do Adulto , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia
6.
Ann Allergy Asthma Immunol ; 127(3): 293-300, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33971364

RESUMO

OBJECTIVE: The classical allergic march model posits that atopy begins in infancy with atopic dermatitis and progresses to asthma and allergic rhinitis in a subset of individuals. The growing prevalence and severity of allergic diseases have prompted renewed interest in refining this model. This review outlines epidemiologic evidence for the existence of allergic march trajectories (distinct paths of atopy development in individuals); reviews the roles that genetics, environment, and disease endotypes play in determining trajectory outcomes; and discusses the clinical utility of the trajectory model. DATA SOURCES: PubMed search of English-language articles and reviews without date limits pertaining to the epidemiology, genetics, and immunologic mechanisms of allergic march trajectories and disease endotypes. STUDY SELECTIONS: Studies and reviews were selected based on their high quality and direct relevance to the review topic. RESULTS: Recent work in the field has revealed that immunoglobulin E-mediated food allergy and eosinophilic esophagitis are components of the allergic march. Furthermore, the field is acknowledging that variability exists in the number and sequence of allergic manifestations that individuals develop. These allergic march pathways, or trajectories, are influenced by genetic, environmental, and psychosocial factors that are incompletely understood. CONCLUSION: Continued elucidation of the landscape and origins of allergic march trajectories will inform efforts to personalize allergic disease prevention, diagnosis, and treatment.


Assuntos
Hipersensibilidade , Exposição Ambiental , Predisposição Genética para Doença , Humanos , Hipersensibilidade/complicações , Hipersensibilidade/epidemiologia , Hipersensibilidade/genética , Hipersensibilidade/terapia , Risco
9.
Allergy Asthma Proc ; 42(3): 187-197, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33980331

RESUMO

Background: Both, allergen immunotherapy (AIT) and SARS-COV-2 infection cause a set of immunologic changes that respectively vary during the course of the treatment or the disease. Objective: To review immune changes brought along by each of these entities and how they might interrelate. Methods: We start presenting a brief review of the structure of the new coronavirus and how it alters the functioning of the human immune system. Subsequently, we describe the immune changes induced by AIT and how these changes could be favorable or unfavorable in the allergic patient infected with SARS-CoV-2 at a particular point of time during the evolving infection. Results: We describe how a healthy immune response against SARS-CoV-2 develops, versus an immune response that is initially suppressed by the virus, but ultimately overactivated, leading to an excessive production of cytokines (cytokine-storm-like). These changes are then linked to the clinical manifestations and outcomes of the patient. Reviewing the immune changes secondary to AIT, it becomes clear how AIT is capable of restoring a healthy innate immunity. Investigators have previously shown that the frequency of respiratory infections is reduced in allergic patients treated with AIT. On the other hand it also increases immunoregulation. Conclusion: As there are many variables involved, it is hard to predict how AIT could influence the allergic patient's reaction to a SARS-CoV-2 infection. In any case, AIT is likely to be beneficial for the patient with allergic rhinitis and/or allergic asthma in the context of the SARS-CoV-2 pandemic as controlling allergic diseases leads to a reduced need for contact with healthcare professionals. The authors remind the reader that everything in this article is still theoretical, since at the moment, there are no published clinical trials on the outcome of COVID-19 in allergic patients under AIT.


Assuntos
COVID-19/imunologia , Dessensibilização Imunológica/métodos , Hipersensibilidade/imunologia , SARS-CoV-2/fisiologia , Biomarcadores Farmacológicos , COVID-19/terapia , Síndrome da Liberação de Citocina , Humanos , Hipersensibilidade/terapia , Modelos Imunológicos
11.
Int Arch Allergy Immunol ; 182(5): 365-380, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33845475

RESUMO

T helper (TH) cells have evolved into distinct subsets that mediate specific immune responses to protect the host against a myriad of infectious and noninfectious challenges. However, if dysregulated, TH-cell subsets can cause inflammatory disease. Emerging evidence now suggests that human allergic disease is caused by a distinct subpopulation of pathogenic TH2 cells. Pathogenic TH2 cells from different type-2-driven diseases share a core phenotype and show overlapping functional attributes. The unique differentiation requirements, activating signals, and metabolic characteristics of pathogenic TH2 cells are just being discovered. A better knowledge of this particular TH2 cell population will enable the specific targeting of disease-driving pathways in allergy. In this review, we introduce a rational for classifying TH cells into distinct subsets, discuss the current knowledge on pathogenic TH2 cells, and summarize their involvement in allergic diseases.


Assuntos
Hipersensibilidade/etiologia , Hipersensibilidade/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Animais , Biomarcadores , Diferenciação Celular , Movimento Celular/imunologia , Citocinas/metabolismo , Suscetibilidade a Doenças , Metabolismo Energético , Regulação da Expressão Gênica , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Memória Imunológica , Imunofenotipagem , Ativação Linfocitária/imunologia , Especificidade de Órgãos/imunologia
12.
Biomaterials ; 273: 120798, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33895493

RESUMO

Despite the important roles of dendritic cells (DCs) in airway allergies, current therapeutic strategies such as drugs, allergen immunotherapy and biologics haven't been targeted at them. In this study, we established a promising DC-based therapeutic approach for the alleviation of allergic rhinitis (AR)-associated allergic reactions, using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated targeted gene disruption. RNA sequencing analysis revealed upregulation of vacuolar protein sorting 37 B (VPS37B) in AR-derived DCs, indicating a novel molecular target. Following antigen presentation, VPS37A and VPS37B enabled endocytosis of the mannose receptor, which recognizes the house dust mite (HDM) allergen Der p 1. DCs with targeted disruption of VPS37A/B alleviated Th2 cytokine production when co-cultured in vitro with allogeneic naïve CD4+ T cell from patients with AR. Furthermore, nasal administration of Vps37a/b-disrupted bone marrow DCs to a mouse model of AR resulted in strongly reduced AR-related symptoms. Thus, this novel modality using genetically engineered DCs can provide an effective therapeutic and preventative strategy for allergic diseases.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Hipersensibilidade , Animais , Antígenos de Dermatophagoides , Células Dendríticas , Humanos , Hipersensibilidade/terapia , Camundongos , Células Th2
13.
Front Immunol ; 12: 609029, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868229

RESUMO

Due to its richness in antigen presenting cells, e.g., dendritic cells (DC), the skin has been identified as a promising route for immunotherapy and vaccination. Several years ago, a skin delivery system was developed based on epicutaneous patches allowing the administration of antigen through intact skin. Using mouse models, we have shown that epicutaneous allergen application leads to a rapid uptake and transport of allergen-positive cells to skin-draining lymph nodes (LN). This occurred primarily in animals previously sensitized to the same allergen. In that context, we sought to better understand the role of the specific preexisting immunity in allergen capture by skin DC and their subsequent migration to LN. Specifically, we investigated the role of humoral immunity induced by sensitization and the involvement of IgG Fc receptors (FcγR). Epicutaneous patches containing fluorescently-labeled ovalbumin (OVA) were applied to naïve mice that had previously received either sera or purified IgG isolated from OVA-sensitized mice. To investigate the involvement of FcγR, animals received 2.4G2 (anti-FcγRII/RIII) blocking antibody, 24 hours before patch application. Mice that received sera or purified IgG originating from OVA-sensitized mice showed an increase in the quantity of OVA-positive DC in skin and LN. Moreover, the blockade of FcγR reduced the number of OVA-positive DC in LN to a level similar to that observed in naïve animals. Overall, these results demonstrate that preexisting specific-IgG antibodies are involved in allergen capture by skin DC following EPIT through the involvement of antigen-specific IgG-FcγR.


Assuntos
Alérgenos/imunologia , Movimento Celular/imunologia , Imunidade Humoral , Células de Langerhans/imunologia , Linfonodos/imunologia , Alérgenos/administração & dosagem , Animais , Biomarcadores , Modelos Animais de Doenças , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Imunização , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Imunofenotipagem , Células de Langerhans/metabolismo , Linfonodos/metabolismo , Camundongos , Receptores Fc/metabolismo
15.
Int J Mol Sci ; 22(6)2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33804685

RESUMO

The skin of an organism is affected by various environmental factors and fights against aging stress via mechanical and biochemical responses. Photoaging induced by ultraviolet B (UVB) irradiation is common and is the most vital factor in the senescence phenotype of skin, and so, suppression of UVB stress-induced damage is critical. To lessen the UVB-induced hyperimmune response and hyperpigmentation, we investigated the ameliorative effects of intense pulsed light (IPL) treatment on the photoaged phenotype of skin cells. Normal human epidermal keratinocytes and human epidermal melanocytes were exposed to 20 mJ/cm2 of UVB. After UVB irradiation, the cells were treated with green (525-530 nm) and yellow (585-592 nm) IPL at various time points prior to the harvest step. Subsequently, various signs of excessive immune response, including expression of proinflammatory and melanogenic genes and proteins, cellular oxidative stress level, and antioxidative enzyme activity, were examined. We found that IPL treatment reduced excessive cutaneous immune reactions by suppressing UVB-induced proinflammatory cytokine expression. IPL treatment prevented hyperpigmentation, and combined treatment with green and yellow IPL synergistically attenuated both processes. IPL treatment may exert protective effects against UVB injury in skin cells by attenuating inflammatory cytokine and melanogenic gene overexpression, possibly by reducing intracellular oxidative stress. IPL treatment also preserves antioxidative enzyme activity under UVB irradiation. This study suggests that IPL treatment is a useful strategy against photoaging, and provides evidence supporting clinical approaches with non-invasive light therapy.


Assuntos
Hipersensibilidade/etiologia , Hipersensibilidade/terapia , Terapia de Luz Pulsada Intensa , Transtornos da Pigmentação/etiologia , Transtornos da Pigmentação/terapia , Raios Ultravioleta/efeitos adversos , Antioxidantes/metabolismo , Biomarcadores , Células Cultivadas , Citocinas/metabolismo , Dermatite/etiologia , Dermatite/metabolismo , Dermatite/patologia , Humanos , Hipersensibilidade/patologia , Melaninas/biossíntese , Estresse Oxidativo/efeitos da radiação , Fototerapia , Pigmentação/efeitos da radiação , Transtornos da Pigmentação/metabolismo , Transtornos da Pigmentação/patologia , Espécies Reativas de Oxigênio/metabolismo , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos da radiação
16.
Ther Umsch ; 78(4): 165-170, 2021.
Artigo em Alemão | MEDLINE | ID: mdl-33899520

RESUMO

Cough from an allergological as well as from the ENT aspect Abstract. Cough is a common problem in the allergological, but less so in the rhinological consultation. The differential diagnostic spectrum for cough is extensive and may range from rhinitis and asthma to eosinophilic esophagitis and rarer diseases. In the case of chronic cough (> 2 months), the four most frequent causes must be sought, or be excluded (upper airway cough syndrome, asthma [cough-variant-asthma], non-asthmatic eosinophilic bronchitis, gastroesophageal reflux disease). Aeroallergens such as pollen, house-dust mites or occupational substances play a major role in allergies. Nevertheless, it is not uncommon for cough to be a main symptom of an antibody deficiency or a Sicca symptom complex. The more chronic the cough, the more thoroughly an investigation is indicated - often interdisciplinary. Therapy depends on the cause of the cough. In allergic respiratory diseases, allergy-specific immunotherapy may be indicated.


Assuntos
Asma , Refluxo Gastroesofágico , Hipersensibilidade , Doença Crônica , Tosse/diagnóstico , Tosse/etiologia , Tosse/terapia , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia
18.
Front Immunol ; 12: 590054, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33708195

RESUMO

Prevalence and incidence of IgE-mediated allergic diseases have increased over the past years in developed and developing countries. Allergen-specific immunotherapy (AIT) is currently the only curative treatment available for allergic diseases that has long-term efficacy. Although AIT has been proven successful as an immunomodulatory therapy since its beginnings, it still faces several unmet needs and challenges today. For instance, some patients can experience severe side effects, others are non-responders, and prolonged treatment schedules can lead to lack of patient adherence and therapy discontinuation. A common strategy to improve AIT relies on the use of adjuvants and immune modulators to boost its effects and improve its safety. Among the adjuvants tested for their clinical efficacy, CpG oligodeoxynucleotide (CpG-ODN) was investigated with limited success and without reaching phase III trials for clinical allergy treatment. However, recently discovered immune tolerance-promoting properties of CpG-ODN place this adjuvant again in a prominent position as an immune modulator for the treatment of allergic diseases. Indeed, it has been shown that the CpG-ODN dose and concentration are crucial in promoting immune regulation through the recruitment of pDCs. While low doses induce an inflammatory response, high doses of CpG-ODN trigger a tolerogenic response that can reverse a pre-established allergic milieu. Consistently, CpG-ODN has also been found to stimulate IL-10 producing B cells, so-called B regulatory cells (Bregs). Accordingly, CpG-ODN has shown its capacity to prevent and revert allergic reactions in several animal models showing its potential as both preventive and active treatment for IgE-mediated allergy. In this review, we describe how CpG-ODN-based therapies for allergic diseases, despite having shown limited success in the past, can still be exploited further as an adjuvant or immune modulator in the context of AIT and deserves additional attention. Here, we discuss the past and current knowledge, which highlights CpG-ODN as a potential adjuvant to be reevaluated for the enhancement of AIT when used in appropriate conditions and formulations.


Assuntos
Adjuvantes Imunológicos , Alérgenos/imunologia , Dessensibilização Imunológica , Tolerância Imunológica , Oligodesoxirribonucleotídeos , Alérgenos/administração & dosagem , Animais , Linfócitos B Reguladores/imunologia , Linfócitos B Reguladores/metabolismo , Biomarcadores , Dessensibilização Imunológica/métodos , Gerenciamento Clínico , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Hipersensibilidade/terapia , Imunoglobulina E/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Receptores Toll-Like/metabolismo
19.
J Biol Chem ; 296: 100585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33771560

RESUMO

House dust mites (HDMs) are a potent allergen source that are commonly found in human living environments. While HDMs are known to induce allergic diseases in humans, such as asthma, its other biological activities related to human health are less understood. Our laboratory recently purified the HDM protein PDI (protein disulfide isomerase). In this study, we assess the role of PDI in contributing to immune regulation. Using mass spectrometry, we analyzed the complexes of DEC205 and HDM extracts, and the role of PDI in the induction of tolerogenic dendritic cells (DCs) was assessed in human cell culture experiments and verified in a murine model. We found that more than 20 HDM-derived proteins, including PDI, bound to DCs by forming complexes with DEC205. Additionally, DEC205-mediated the endocytosis of PDI. HDM-derived PDI (HDM-PDI) promoted Foxp3 expression in DCs. HDM-PDI-primed DCs also showed tolerogenic properties that induced regulatory T cell development, indicating that the primed DCs were tolerogenic DCs. Our results suggested that the PDI/DEC205/TIEG1/Foxp3 signal pathway activation was involved in the HDM-PDI-induced Foxp3 expression in DCs. Finally, we found that HDM-PDI competitively counteracted the Th2 cytokines to restore DC's tolerogenicity, and administration of HDM-PDI could suppress experimental asthma. In conclusion, our data suggest that HDM-PDI contributes to immune regulation by inducing tolerogenic DC development. Administration of HDM-PDI can alleviate experimental asthma. These findings demonstrate that HDM-PDI has translational potential to be used in the treatment of immune disorders such as asthma.


Assuntos
Células Dendríticas/imunologia , Hipersensibilidade/terapia , Isomerases de Dissulfetos de Proteínas/metabolismo , Pyroglyphidae/enzimologia , Sistema Respiratório/imunologia , Animais , Citocinas/metabolismo , Células Dendríticas/metabolismo , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Camundongos
20.
J Allergy Clin Immunol Pract ; 9(5): 1780-1789, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33753052

RESUMO

Allergen immunotherapy (AIT) is the only setting in which a vaccine is applied in patients allergic exactly to the active principle in the vaccine. Therefore, AIT products need to be not only effective but also safe. In Europe, for subcutaneous AIT, this has been achieved by the allergoid strategy in which IgE epitopes are destroyed or masked. In addition, adjuvants physically precipitate the allergen at the injection site to prevent too rapid systemic distribution. The choice of adjuvant critically shapes the efficacy and type of immune response to the injected allergen. In contrast to TH2-promoting adjuvants, others clearly counteract allergy. Marketed products in Europe are formulated with aluminum hydroxide (alum) (66.7%), microcrystalline tyrosine (16.7%), calcium phosphate (11.1%), or the TH1 adjuvant monophosphoryl lipid A (5.6%). In contrast to the European practice, in the United States mostly nonadjuvanted extracts and no allergoids are used for subcutaneous AIT, highlighting not only a regulatory but maybe a "historic preference." Sublingual AIT in the form of drops or tablets is currently applied worldwide without adjuvants, usually with higher safety but lower patient adherence than subcutaneous AIT. This article will discuss how AIT and adjuvants modulate the immune response in the treated patient toward immune activation, modulation, or-with new developments in the pipeline-immune resilience.


Assuntos
Hipersensibilidade , Imunoterapia Sublingual , Alérgenos , Dessensibilização Imunológica , Europa (Continente) , Humanos , Hipersensibilidade/terapia
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