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2.
Nature ; 584(7821): 463-469, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32717743

RESUMO

Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1-4. However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. By contrast, patients with severe COVID-19 maintained these elevated responses throughout the course of the disease. Moreover, severe COVID-19 was accompanied by an increase in multiple type 2 (anti-helminths) effectors, including interleukin-5 (IL-5), IL-13, immunoglobulin E and eosinophils. Unsupervised clustering analysis identified four immune signatures, representing growth factors (A), type-2/3 cytokines (B), mixed type-1/2/3 cytokines (C), and chemokines (D) that correlated with three distinct disease trajectories. The immune profiles of patients who recovered from moderate COVID-19 were enriched in tissue reparative growth factor signature A, whereas the profiles of those with who developed severe disease had elevated levels of all four signatures. Thus, we have identified a maladapted immune response profile associated with severe COVID-19 and poor clinical outcome, as well as early immune signatures that correlate with divergent disease trajectories.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Citocinas/análise , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Citocinas/imunologia , Eosinófilos/imunologia , Feminino , Humanos , Imunoglobulina E/análise , Imunoglobulina E/imunologia , Interleucina-13/análise , Interleucina-13/imunologia , Interleucina-5/análise , Interleucina-5/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Linfócitos T/citologia , Linfócitos T/imunologia , Carga Viral , Adulto Jovem
3.
Proc Natl Acad Sci U S A ; 117(30): 18068-18078, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32661165

RESUMO

Mast cells and basophils are main drivers of allergic reactions and anaphylaxis, for which prevalence is rapidly increasing. Activation of these cells leads to a tightly controlled release of inflammatory mediators stored in secretory granules. The release of these granules is dependent on intracellular calcium (Ca2+) signals. Ca2+ release from endolysosomal compartments is mediated via intracellular cation channels, such as two-pore channel (TPC) proteins. Here, we uncover a mechanism for how TPC1 regulates Ca2+ homeostasis and exocytosis in mast cells in vivo and ex vivo. Notably, in vivo TPC1 deficiency in mice leads to enhanced passive systemic anaphylaxis, reflected by increased drop in body temperature, most likely due to accelerated histamine-induced vasodilation. Ex vivo, mast cell-mediated histamine release and degranulation was augmented upon TPC1 inhibition, although mast cell numbers and size were diminished. Our results indicate an essential role of TPC1 in endolysosomal Ca2+ uptake and filling of endoplasmic reticulum Ca2+ stores, thereby regulating exocytosis in mast cells. Thus, pharmacological modulation of TPC1 might blaze a trail to develop new drugs against mast cell-related diseases, including allergic hypersensitivity.


Assuntos
Anafilaxia/etiologia , Anafilaxia/metabolismo , Canais de Cálcio/deficiência , Suscetibilidade a Doenças , Mastócitos/imunologia , Mastócitos/metabolismo , Biomarcadores , Sinalização do Cálcio , Degranulação Celular , Citocinas/metabolismo , Predisposição Genética para Doença , Histamina/metabolismo , Imunoglobulina E/imunologia , Mediadores da Inflamação/metabolismo
4.
Nature ; 584(7821): 463-469, 2020 08.
Artigo em Inglês | MEDLINE | ID: covidwho-677004

RESUMO

Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1-4. However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. By contrast, patients with severe COVID-19 maintained these elevated responses throughout the course of the disease. Moreover, severe COVID-19 was accompanied by an increase in multiple type 2 (anti-helminths) effectors, including interleukin-5 (IL-5), IL-13, immunoglobulin E and eosinophils. Unsupervised clustering analysis identified four immune signatures, representing growth factors (A), type-2/3 cytokines (B), mixed type-1/2/3 cytokines (C), and chemokines (D) that correlated with three distinct disease trajectories. The immune profiles of patients who recovered from moderate COVID-19 were enriched in tissue reparative growth factor signature A, whereas the profiles of those with who developed severe disease had elevated levels of all four signatures. Thus, we have identified a maladapted immune response profile associated with severe COVID-19 and poor clinical outcome, as well as early immune signatures that correlate with divergent disease trajectories.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Citocinas/análise , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Citocinas/imunologia , Eosinófilos/imunologia , Feminino , Humanos , Imunoglobulina E/análise , Imunoglobulina E/imunologia , Interleucina-13/análise , Interleucina-13/imunologia , Interleucina-5/análise , Interleucina-5/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Linfócitos T/citologia , Linfócitos T/imunologia , Carga Viral , Adulto Jovem
5.
Allergol. immunopatol ; 48(3): 251-258, mayo-jun. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-192027

RESUMO

INTRODUCTION AND OBJECTIVES: Allergy to galactose-α-1,3-galactose (alpha-gal) is a peculiar form of food allergy generally manifesting as an anaphylactic reaction hours after mammalian meat consumption, due to the presence of specific IgE against this oligosaccharide. In addition, immediate anaphylaxis may develop after exposure to other sources of alpha-gal, such as monoclonal antibody cetuximab, vaccines, plasma expanders or anti-snake venoms. Sensitization to alpha-gal has also been implicated in the rapid degeneration of biological valve implants, and recognized as a cause of occupational disease in cattle raisers. The implication of tick bites in this type of sensitization has been accepted by all the research groups dedicated to this disease. PATIENTS AND METHOD: The present study describes the clinical and sensitization characteristics of 39 patients diagnosed with alpha-gal allergy in the hospitals of our province (Lugo, Monforte de Lemos and Burela, Spain). RESULTS: Most patients were middle-age males. Of note, is the fact that the series includes the first pediatric patient reported in Spain to date. The predominant clinical manifestations were urticaria or delayed anaphylaxis after consumption of mammalian meat. Seventy-four percent of the patients reported having suffered a previous tick bite, and the clinical presentation of anaphylaxis was significantly more prevalent in those with a persistent local reaction following the bite than in those with no such reaction (p = 0.032). CONCLUSIONS: A review is also made of the disorder which, due to its variable clinical expression, is referred to as alpha-gal syndrome. The study concludes that a diagnosis of alpha-gal allergy should be considered in patients with urticaria-anaphylaxis of uncertain origin or manifesting after the administration of vaccines or products of bovine/porcine origin


No disponible


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Galactose/imunologia , Hipersensibilidade Alimentar/imunologia , Alérgenos/imunologia , Hipersensibilidade Alimentar/diagnóstico , Galactose/efeitos adversos , Hipersensibilidade Tardia/imunologia , Espanha , Imunoglobulina E/imunologia , Anafilaxia/imunologia , Testes Cutâneos , Anticorpos Monoclonais/imunologia
8.
PLoS One ; 15(6): e0233707, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32484810

RESUMO

Royal jelly (RJ), a creamy substance secreted by honeybees, is the exclusive diet for queen bee differentiation and life maintenance. RJ has been used in cosmetics, beverages, medicines, and supplements worldwide. However, allergy is a concerning issue for RJ, especially in atopic dermatitis (AD) and asthma patients. In some cases, allergic reactions are seen after the first intake of RJ, suggesting the existence of allergens cross-reactive with RJ. Information about the cross-reactive allergens is very important for the safe application of RJ; however, study of this cross-reactivity is quite limited. In this study, we attempted to identify allergens cross-reactive with RJ by using serum samples from 30 AD patients who had never been exposed to RJ. In an enzyme-linked immunosorbent assay (ELISA) experiment, RJ-binding IgE antibodies were detected in the serum of 10 out of 30 patients, and their antibody titers ranged from 4- to 2,048-fold dilution ratios. Additionally, 3 AD patients were determined to be positive in a skin-prick test (SPT) with an RJ solution. Significant correlations were observed between the anti-RJ antibody titer and nonspecific IgE and between the anti-RJ antibody titer and the Eczema Area and Severity Index score. We further examined the cross-reactivity between RJ and 14 typical allergens by using an ELISA-inhibition assay and demonstrated that the following 6 allergens showed cross-reactivity with RJ: the European house dust mite (HDM) (Dermatophagoides pteronyssinus), American HDM (Dermatophagoides farinae), snow crab (Chionocetes spp.), edible crab (Cancer pagurus), German cockroach (Blatella germanica), and honeybee venom (Apis mellifera). In conclusion, people with a history of allergic diseases, including AD, asthma, and allergic rhinitis, should be cautioned against consuming RJ products because of the potential for cross-reactive responses to ensure the safe and successful use of RJ supplements.


Assuntos
Alérgenos/imunologia , Abelhas/imunologia , Dermatite Atópica/imunologia , Ácidos Graxos/imunologia , Adulto , Animais , Antígenos de Dermatophagoides/imunologia , Venenos de Abelha/imunologia , Blattellidae/imunologia , Braquiúros/imunologia , Reações Cruzadas , Dermatite Atópica/sangue , Dermatite Atópica/diagnóstico , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Frutos do Mar , Testes Cutâneos , Adulto Jovem
9.
Nature ; 582(7811): 265-270, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32499653

RESUMO

Approximately one-third of the world's population suffers from allergies1. Exposure to allergens crosslinks immunoglobulin E (IgE) antibodies that are bound to mast cells and basophils, triggering the release of inflammatory mediators, including histamine2. Although IgE is absolutely required for allergies, it is not understood why total and allergen-specific IgE concentrations do not reproducibly correlate with allergic disease3-5. It is well-established that glycosylation of IgG dictates its effector function and has disease-specific patterns. However, whether IgE glycans differ in disease states or affect biological activity is completely unknown6. Here we perform an unbiased examination of glycosylation patterns of total IgE from individuals with a peanut allergy and from non-atopic individuals without allergies. Our analysis reveals an increase in sialic acid content on total IgE from individuals with a peanut allergy compared with non-atopic individuals. Removal of sialic acid from IgE attenuates effector-cell degranulation and anaphylaxis in several functional models of allergic disease. Therapeutic interventions-including removing sialic acid from cell-bound IgE with a neuraminidase enzyme targeted towards the IgE receptor FcεRI, and administering asialylated IgE-markedly reduce anaphylaxis. Together, these results establish IgE glycosylation, and specifically sialylation, as an important regulator of allergic disease.


Assuntos
Imunoglobulina E/química , Imunoglobulina E/imunologia , Ácido N-Acetilneuramínico/análise , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade a Amendoim/patologia , Adolescente , Adulto , Idoso , Alérgenos/imunologia , Anafilaxia/imunologia , Animais , Estudos de Casos e Controles , Degranulação Celular/imunologia , Criança , Pré-Escolar , Feminino , Glicosilação , Humanos , Imunoglobulina E/efeitos adversos , Imunoglobulina E/farmacologia , Lactente , Recém-Nascido , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Imunológicos , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/metabolismo , Neuraminidase/metabolismo , Receptores de IgE/metabolismo , Adulto Jovem
10.
Food Chem ; 326: 127027, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32438232

RESUMO

This work reports on theeffect of heat treatment on the protein conformational stabilityof intact and post-translationallycleaved peanut allergen Ara h 6 in relation to IgE-binding. Intact and post-translationallycleaved Ara h 6 are structurally similar and theirstrong resistance to denaturant-inducedunfolding is comparable. Only upon exposure toautoclave conditions the twoforms of Ara h 6 demonstrated susceptibility toirreversible denaturationresulting in a significant decrease in IgE-binding potency. Thisreduction isfor the intact protein more pronounced than for than for the cleaved form. This isattributed to less conformational constrains of the cleaved form comparedtointact, as suggested by the 2-fold lower activation energy for unfoldingfound for the cleavedform. Overall, harsh conditionsare required to denature Ara h 6 and to significantly reduce its IgE-bindingpotency. The cleavedform possesses more resistance to such denaturation than the intactform.


Assuntos
Albuminas 2S de Plantas/química , Alérgenos/química , Antígenos de Plantas/química , Arachis/química , Imunoglobulina E/imunologia , Albuminas 2S de Plantas/imunologia , Alérgenos/imunologia , Antígenos de Plantas/imunologia , Temperatura Alta , Conformação Proteica , Fatores de Tempo
11.
Food Chem ; 327: 127037, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32446030

RESUMO

In this work, the mechanism of the effect of lipid oxidation on the IgG/IgE binding ability of ovalbumin (OVA) was investigated via the peroxyl radicals produced by 2, 2'-azobis (2-amidinopropane) dihydrochloride to simulate lipid oxidation. Results showed that the structure of OVA unfolded partially with an increase in oxidation degree, leading to the exposure of the allergenic epitopes and increasing the IgG/IgE binding ability of OVA. Nine oxidation sites were found on the α-helix, and these sites may unwind the α-helix and expose the allergenic epitopes on the OVA surface, leading to antibody recognition and combination. Consequently, the IgG/IgE binding ability of OVA was increased. In conclusion, the allergenic capacity of OVA can be promoted by modifying peroxyl radical oxidation in processing egg products.


Assuntos
Amidinas/metabolismo , Biomimética , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Metabolismo dos Lipídeos , Ovalbumina/imunologia , Ovalbumina/metabolismo , Animais , Oxirredução
12.
Proc Natl Acad Sci U S A ; 117(23): 12980-12990, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32461368

RESUMO

The aryl hydrocarbon receptor (AhR) represents an environmental sensor regulating immune responses. In the skin, AhR is expressed in several cell types, including keratinocytes, epidermal Langerhans cells (LC), and dermal dendritic cells (DC). The mechanisms how AhR activates or inhibits cutaneous immune responses remain controversial, owing to differences in the cell-specific functions of AhR and the different activating ligands. Therefore, we sought to investigate the role of AhR in LC and langerin+ and negative DC in the skin. To this aim, we generated Langerin-specific and CD11c-specific knockout (-/-) mice lacking AhR, respectively, in LC and Langerin+ dermal DC and in all CD11c+ cells. These were then tested in an epicutaneous protein (ovalbumin, Ova) sensitization model. Immunofluorescence microscopy and flow cytometry revealed that Langerin-AhR-/- but not CD11c-AhR-/- mice harbored a decreased number of LC with fewer and stunted dendrites in the epidermis as well as a decreased number of LC in skin-draining lymph nodes (LN). Moreover, in the absence of AhR, we detected an enhanced T helper type-2 (Th2) [increased interleukin 5 (IL-5) and interleukin 13 (IL-13)] and T regulatory type-1 (Tr1) (IL-10) response when LN cells were challenged with Ova in vitro, though the number of regulatory T cells (Treg) in the LN remained comparable. Langerin-AhR-/- mice also exhibited increased blood levels of Ova-specific immunoglobulin E (IgE). In conclusion, deletion of AhR in langerin-expressing cells diminishes the number and activation of LC, while enhancing Th2 and Tr1 responses upon epicutaneous protein sensitization.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células de Langerhans/imunologia , Receptores de Hidrocarboneto Arílico/metabolismo , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Administração Cutânea , Animais , Antígenos de Superfície/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Epiderme/imunologia , Epiderme/metabolismo , Técnicas de Inativação de Genes , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Células de Langerhans/metabolismo , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/metabolismo , Camundongos , Camundongos Transgênicos , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Receptores de Hidrocarboneto Arílico/genética , Linfócitos T Reguladores/metabolismo , Células Th2/metabolismo
13.
Am J Med Sci ; 360(2): 137-145, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32423746

RESUMO

BACKGROUND: At present, the effect of operation intervention on pulmonary function is not clear in patients with allergic rhinitis and chronic rhinosinusitis with nasal polyps (AR&CRSwNP). This study was conducted to investigate the effect of vidian neurectomy on pulmonary function and airway hyperresponsiveness (AHR) in patients with AR&CRSwNP. METHODS: The incidences of AHR, bronchial asthma (BA) and pulmonary function impairment in 112 patients with AR&CRSwNP were investigated. Subsequently, we evaluated the outcome of vidian neurectomy and its effect on pulmonary function and AHR. Furthermore, we explored the correlation between postoperative level of eosinophilic cationic protein (ECP) and the changes of pulmonary function indices or dose of methacholine. RESULTS: In this study, the incidences of pulmonary function impairment, bronchial asthma, and AHR in patients with AR&CRSwNP were 61.61%, 69.64%, and 66.96%, respectively. Particularly, vidian neurectomy effectively alleviated nasal symptoms, improved pulmonary function, and reduced AHR in AR&CRSwNP patients. Furthermore, the postoperative level of ECP, IgE, Interleukin-4 and Interleukin-IL-5 was dramatically decreased, and there was an obvious inverse correlation between ECP level and pulmonary function index or dose of methacholine. CONCLUSIONS: Vidian neurectomy is effective in alleviating nasal symptoms, improving pulmonary function, and reducing the risk of AHR of patients with AR&CRSwNP by decreasing the level of ECP.


Assuntos
Denervação/métodos , Gânglio Geniculado/cirurgia , Pólipos Nasais/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Rinite Alérgica/cirurgia , Sinusite/cirurgia , Adulto , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/fisiopatologia , Testes de Provocação Brônquica , Doença Crônica , Proteína Catiônica de Eosinófilo/imunologia , Feminino , Volume Expiratório Forçado , Humanos , Imunoglobulina E/imunologia , Interleucina-4/imunologia , Interleucina-5/imunologia , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/imunologia , Pólipos Nasais/fisiopatologia , Complicações Pós-Operatórias/epidemiologia , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/fisiopatologia , Rinite Alérgica/imunologia , Rinite Alérgica/fisiopatologia , Sinusite/imunologia , Sinusite/fisiopatologia , Resultado do Tratamento , Capacidade Vital
14.
PLoS One ; 15(5): e0233537, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32442209

RESUMO

Human IgE-binding monocytes are identified as allergic disease mediators, but it is unknown whether IgE-binding monocytes promote or prevent an allergic response. We identified IgE-binding monocytes in equine peripheral blood as IgE+/MHCIIhigh/CD14low cells that bind IgE through an FcεRI αÉ£ variant. IgE-binding monocytes were analyzed monthly in Culicoides hypersensitive horses and nonallergic horses living together with natural exposure to Culicoides midges. The phenotype and frequency of IgE-binding monocytes remained consistent in all horses regardless of Culicoides exposure. All horses upregulated IgE-binding monocyte CD16 expression following initial Culicoides exposure. Serum total IgE concentration and monocyte surface IgE densities were positively correlated in all horses. We also demonstrated that IgE-binding monocytes produce IL-10, but not IL-4, IL-17A, or IFN-γ, following IgE crosslinking. In conclusion, we have characterized horse IgE-binding monocytes for the first time and further studies of these cells may provide important connections between regulation and cellular mechanisms of IgE-mediated diseases.


Assuntos
Ceratopogonidae/imunologia , Doenças dos Cavalos/imunologia , Hipersensibilidade Imediata/veterinária , Imunoglobulina E/imunologia , Mordeduras e Picadas de Insetos , Leucócitos Mononucleares , Alérgenos/imunologia , Animais , Antígenos de Superfície/imunologia , Citocinas/metabolismo , Cavalos , Imunoglobulina E/sangue , Mordeduras e Picadas de Insetos/imunologia , Mordeduras e Picadas de Insetos/veterinária , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Receptores de IgE/imunologia
15.
Ann Allergy Asthma Immunol ; 125(3): 325-333.e1, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32353405

RESUMO

BACKGROUND: Hypersensitivity reactions to antineoplastic agents may lead to discontinuation of first-line treatments. Rapid drug desensitization (RDD) allows for a safe reintroduction in patients who are allergic to them. OBJECTIVE: To evaluate the safety and efficacy of the Brigham and Women's Hospital's 12-step RDD in a Portuguese patient population with cancer and to identify markers associated with breakthrough reactions (BTRs) to platins. METHODS: We conducted a retrospective review of desensitizations undertaken at the Immunoallergology Day-Care Unit of the Santa Maria Hospital in Lisbon, Portugal, from July 2008 to July 2019. Adult patients with cancer and with immediate hypersensitivity reactions were included. Skin testing was performed to platins, trastuzumab, and cetuximab. The 12-step protocol was used for most patients, and a shorter protocol was used in 9 patients who were taxane-reactive to resume regular infusions. RESULTS: A total of 1471 RDDs were performed in 272 patients to 136 platins, 124 taxanes, 13 monoclonal antibodies, and 10 other drugs. Skin test results were positive in 127 of patients who were platin-reactive (95.3%) and negative in patients who were cetuximab- and trastuzumab-reactive. There were 141 BTRs during RDD (9.6% of infusions), 79.4% induced by platins with the majority having mild reactions (68.8%). There were 8 patients who were paclitaxel-reactive, and who completed a shorter protocol and resumed regular infusions successfully. Multiple platin infusions (cutoff: ≥10) and total immunoglobulin E greater than or equal to 100 U/mL were identified as independent risk factors for BTRs in patients who were platin-reactive. CONCLUSION: This large single-center study confirmed the safety and efficacy of the 12-step RDD protocol in a diverse cancer population, providing evidence of its universal applications. Total immunoglobulin E is a potentially useful biomarker to identify high-risk patients who are platin-reactive.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/imunologia , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/imunologia , Neoplasias/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Antineoplásicos/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/imunologia , Cetuximab/efeitos adversos , Cetuximab/imunologia , Dessensibilização Imunológica/métodos , Feminino , Humanos , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Pacientes Ambulatoriais , Paclitaxel/efeitos adversos , Paclitaxel/imunologia , Portugal , Estudos Retrospectivos , Fatores de Risco , Testes Cutâneos/métodos , Taxoides/efeitos adversos , Taxoides/imunologia , Trastuzumab/efeitos adversos , Trastuzumab/imunologia , Adulto Jovem
16.
Food Chem ; 321: 126679, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32247887

RESUMO

Although pizza is one of the most popular foods in the world, allergic responses after ingesting pizza are relatively uncommon. However, precisely identifying the allergens responsible for these allergic reactions is challenging because of the high and diverse number of ingredients used in pizza preparation. In this report, we aim to identify the allergens responsible for systemic allergic reactions following ingestion of pizza in two patients. Using a skin prick by prick test (SPPT) and in vitro techniques, with natural and recombinant purified allergens from tomato and mustard seeds, we identified 2S albumin and non-specific lipid transfer proteins (nsLTP) as the proteins involved. However, IgE responses to the four nsLTPs differed before and after denaturation and reduction, thus suggesting additional complexity around nsLTP in food processing.


Assuntos
Albuminas/imunologia , Anafilaxia/imunologia , Antígenos de Plantas/imunologia , Proteínas de Transporte/imunologia , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/imunologia , Anafilaxia/etiologia , Pré-Escolar , Hipersensibilidade Alimentar/complicações , Humanos , Lycopersicon esculentum/imunologia , Masculino , Mostardeira/imunologia , Sementes/imunologia , Testes Cutâneos , Adulto Jovem
17.
PLoS One ; 15(4): e0231344, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32324770

RESUMO

BACKGROUND: Cross-reactive carbohydrate determinant (CCD) structures found in plant and insect glycoproteins are commonly recognized by IgE antibodies as epitopes that can lead to extensive cross-reactivity and obscure in vitro diagnostic (IVD) serology results. With the introduction of component resolved diagnosis (CRD), recombinant non-glycosylated components have been utilized to mitigate the risk of CCD-specific IgE (sIgE) detection. However, a recent study has shown that CCD-sIgE may bind directly to the cellulose solid phase matrix used in certain in vitro diagnostic assays, eliminating the advantage of CRD over traditional extract-based testing. The aim of this study is to further investigate the prevalence of CCD-sIgE interference on a commonly-used in vitro sIgE automated platform which employs a cellulose-based matrix to immobilize CCD-free recombinant components. METHODS: Sera from patients sensitized to peanut, silver birch, and/or timothy grass were analyzed for CCD-sIgE reactivity on ImmunoCAP/Phadia and NOVEOS autoanalyzers against the MUXF3 carbohydrate component. Positive CCD-sIgE sera were further analyzed against non-glycosylated recombinant components bound to the ImmunoCAP solid phase in the absence and presence of a soluble CCD inhibitor. For comparison, sera were then analyzed on NOVEOS, a non-cellulose based automated sIgE assay. RESULTS: Sera from 35% of the sensitized population tested in this study were positive (≥0.35 kU/L) for CCD-sIgE. Of those positives, 17% resulted in CCD-sIgE-positive (false positive) results on ImmunoCAP using non-glycosylated allergosorbents that were negative on NOVEOS. Sera producing false-positive results on ImmunoCAP had varying levels of CCD-sIgE from 0.67 kU/L to 36.52 kU/L. The incidence of CCD interference was predominantly delimited to low-positive IgE results (0.35 kUA/L- 3.00 kUA/L). CONCLUSION: Falsely elevated diagnostic allergen-sIgE results can commonly occur due to the presence of CCD-sIgE using assays that employ a carbohydrate matrix-based allergosorbent. Even the use of non-glycosylated recombinant allergenic components coupled to cellulose matrices do not reduce their risk of detection. The risk of CCD interference that compromises quantitative IgE results can be mitigated by the addition of a soluble CCD inhibitor to positive CCD-sIgE containing sera or by alternatively using a non-cellulose based sIgE assay, such as the NOVEOS assay.


Assuntos
Alérgenos/imunologia , Celulose/imunologia , Imunoglobulina E/imunologia , Alérgenos/genética , Alérgenos/metabolismo , Arachis/imunologia , Betula/imunologia , Reações Cruzadas , Humanos , Hipersensibilidade/sangue , Hipersensibilidade/patologia , Imunoglobulina E/sangue , Phleum/imunologia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/imunologia
18.
Adv Exp Med Biol ; 1279: 27-35, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32266608

RESUMO

Atopic, allergic, and especially asthmatic subjects might be particularly susceptible to sensory irritation induced by airborne chemicals compared to healthy individuals. Therefore, a good characterization of subjects is essential in inhalation exposure studies on sensory irritants. A total of 105 volunteers, 87% of whom reported to be non-allergic, participated in a medical examination that included skin prick test (SPT), measurements of total IgE, specific IgE (sIgE) to an ubiquitous allergen mix (sx1), and fractionated exhaled nitric oxide (FeNO), as well as pulmonary function and methacholine test. The median value of sIgE to sx1 was 0.20 kU/L (0.07-91.3 kU/L) and correlated significantly with total IgE (28.8 kU/L (2-756 kU/L)) and FeNO (14 ppb (5-100 ppb)). Forty-three subjects (41%) had sIgE to sx1 ≥ 0.35 kU/L and were classified as atopic. Thirty-five subjects, all also sx1-positive, were positive in SPT. Obstruction, small airway disease, and/or bronchial hyperreactivity were diagnosed in 18 subjects. Receiver operating characteristics (ROC) were performed to check whether signs of sensitization are useful to discriminate subjects with and without airway diseases. However, sx1, total IgE, FeNO, and SPT reached only low areas under the curve (AUC: 0.57-0.66). Although predominantly young and, according to their own statements, mostly non-allergic subjects participated in the study, almost half of them were atopic, and 10% had airway disease or bronchial hyperreactivity. This indicates that the validity of self-reported data might be inaccurate. In summary, diversified investigations of the allergy-related health status appear necessary for a thorough characterization of subjects for exposure studies on sensory irritants.


Assuntos
Alérgenos/imunologia , Asma/imunologia , Hipersensibilidade Imediata/imunologia , Hipersensibilidade/imunologia , Humanos , Imunoglobulina E/análise , Imunoglobulina E/imunologia , Óxido Nítrico/metabolismo , Sensação/imunologia , Testes Cutâneos , Voluntários
19.
PLoS One ; 15(4): e0231747, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298380

RESUMO

BACKGROUND: Large local reactions (LLR) to Hymenoptera stings were considered as IgE-mediated late-phase inflammatory reactions. However, in older studies, most patients with LLR were skin test positive, but only around 50% had detectable sIgE determined by the RAST system. METHODS: Data of 620 patients were evaluated retrospectively: 310 patients who suffered from LLR and 310 patients with previous systemic sting reactions (SSR). We aimed to clarify if sIgE can generally be detected by the CAP system in patients with LLR; sIgE levels and clinical parameters were compared between patients with LLR and SSR. RESULTS: Positive sIgE levels were detected in 80.7% of patients with LLR, and in 95.2% of patients with SSR (p<0.001). Of the 310 patients with LLR, 80.6% had a LLR with a size of 10-20cm, whereas 19.4% had swellings >20cm, with a mean duration of seven days. In only 2.9% of patients, LLRs occurred after stings on the trunk, while 14.8% of SSR resulted from stings on this site (p<0.001). Similarly, LLR were also less frequent on the capillitium compared to SSR (8.1% versus 26.2%; p = 0.035). CONCLUSIONS: LLR usually persisted over seven days and about one fifth of patients had swellings greater than 20cm. Contrary to SSR, LLR were less frequently observed on the capillitium and on the trunk. In most patients with LLR, sIgE could be detected. However, total IgE and sIgE levels to bee or vespid venom did not differ between patients with LLR and SSR.


Assuntos
Venenos de Abelha/imunologia , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Mordeduras e Picadas de Insetos/imunologia , Venenos de Vespas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos/imunologia , Animais , Criança , Pré-Escolar , Feminino , Humanos , Himenópteros , Hipersensibilidade/imunologia , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Testes Cutâneos , Adulto Jovem
20.
PLoS One ; 15(4): e0231101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32302339

RESUMO

Mast cells and basophils are central players in allergic reactions triggered by immunoglobulin E (IgE). They have intracellular granules containing allergic mediators (e.g., histamine, serotonin, inflammatory cytokines, proteases and ß-hexosaminidase), and stimulation by IgE-allergen complex leads to the release of such allergic mediators from the granules, that is, degranulation. Mast cells are residents of mucosal surfaces, including those of nasal and oral cavities, and play an important role in the innate defense system. Members of the mitis group streptococci such as Streptococcus oralis, are primary colonizers of the human oral cavity. They produce hydrogen peroxide (H2O2) as a by-product of sugar metabolism. In this study, we investigated the effects of streptococcal infection on RBL-2H3 mast cell/basophil cell line. Infection by oral streptococci did not induce degranulation of the cells. Stimulation of the RBL-2H3 cells with anti-dinitrophenol (DNP) IgE and DNP-conjugated human serum albumin triggers degranulation with the release of ß-hexosaminidase. We found that S. oralis and other mitis group streptococci inhibited the IgE-triggered degranulation of RBL-2H3 cells. Since mitis group streptococci produce H2O2, we examined the effect of S. oralis mutant strain deficient in producing H2O2, and found that they lost the ability to suppress the degranulation. Moreover, H2O2 alone inhibited the IgE-induced degranulation. Subsequent analysis suggested that the inhibition of degranulation was related to the cytotoxicity of streptococcal H2O2. Activated RBL-2H3 cells produce interleukin-4 (IL-4); however, IL-4 production was not induced by streptococcal H2O2. Furthermore, an in vivo study using the murine pollen-induced allergic rhinitis model suggested that the streptococcal H2O2 reduces nasal allergic reaction. These findings reveal that H2O2 produced by oral mitis group streptococci inhibits IgE-stimulated degranulation by inducing cell death. Consequently, streptococcal H2O2 can be considered to modulate the allergic reaction in mucosal surfaces.


Assuntos
Alérgenos/metabolismo , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Infecções Estreptocócicas/tratamento farmacológico , Alérgenos/imunologia , Animais , Basófilos/imunologia , Basófilos/microbiologia , Basófilos/patologia , Degranulação Celular/imunologia , Sobrevivência Celular/imunologia , Dinitrofenóis/farmacologia , Humanos , Peróxido de Hidrogênio/metabolismo , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/patologia , Imunoglobulina E/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Mastócitos/imunologia , Mastócitos/microbiologia , Mastócitos/patologia , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Albumina Sérica Humana/imunologia , Albumina Sérica Humana/metabolismo , Infecções Estreptocócicas/imunologia , Streptococcus oralis/imunologia , Streptococcus oralis/patogenicidade , Açúcares/metabolismo
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