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1.
Medicine (Baltimore) ; 99(4): e18557, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977848

RESUMO

BACKGROUND: Anaphylactic rhinitis (AR) is one of the most common allergic disorders globally. Heat-sensitive moxibustion (HSM) is an effective method for AR without the occurrence of drug damage. This study aims to systematically investigate the effectiveness and safety of HSM for patients with AR. METHODS: Seven relevant electronic databases from inception until January 2020 including PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure Database, Wanfang Database, Chinese Biomedical Literature Database, and Chinese Scientific Journal Database will be searched. All relevant randomized clinical trials published in English and Chinese about HSM for AR regardless of blinding or publication types can be included. The Cochrane Central Register of Controlled Trials and other potential articles in the reference list of included studies will also be searched. We recommend total nasal symptom score as primary outcomes. Secondary outcomes includes rhinoconjunctivitis quality of life questionnaire, IgE, visual analogue scale, laboratory examination, and side effects. Study selection, data extraction, and quality assessment will be performed independently by 2 reviewers. Assessment of risk of bias and data synthesis will be conducted by RevMan 5.3 software. ETHICS AND DISSEMINATION: Ethical approval is not required for no personal data involved. The results of this SR will be disseminated through peer-reviewed publications according to the Preferred Reporting Items for Systematic reviews and Meta Analysis Protocols guidelines. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: The findings will provide further evidence for the management of AR. PROSPERO REGISTRATION NUMBER: CRD42019140723.


Assuntos
Moxibustão/métodos , Rinite Alérgica/terapia , Conjuntivite Alérgica/epidemiologia , Humanos , Imunoglobulina E/sangue , Moxibustão/efeitos adversos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Rinite Alérgica/epidemiologia
2.
Scand J Immunol ; 91(1): e12817, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31650620

RESUMO

Nowadays, people pay more attention to biomarkers that can predict clinical efficacy of immunotherapy for allergic rhinitis. As the only recognized aetiological treatment, the efficacy of allergen immunotherapy (AIT) has been proved by many studies. However, treatment success depends on compliance and persistence greatly, which can be impaired by the lengthy duration of AIT and socioeconomic status of patients. Besides, ineffectiveness is another factor that accounts for non-adherence. If the clinical efficacy can be predicted in the early stage of immunotherapy, it can help patients choose appropriate treatment plans, increase patient compliance and optimize the allocation of medical resources. This paper mainly focuses on five candidate biomarkers, the sIgE/tIgE ratio before treatment, serum inhibitory activity for IgE, decreased basophil activation, upregulation of Tregs and tolerogenic DCs, reviews the time when potential biomarkers can predict or monitor the efficacy of AIT, discusses the reason why these indicators could serve as efficacy biomarkers and interactions among potential biomarkers.


Assuntos
Alérgenos/imunologia , Biomarcadores , Dessensibilização Imunológica , Rinite Alérgica/imunologia , Rinite Alérgica/terapia , Animais , Basófilos/imunologia , Basófilos/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Dessensibilização Imunológica/métodos , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Rinite Alérgica/diagnóstico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Resultado do Tratamento
3.
Scand J Immunol ; 91(1): e12835, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31596502

RESUMO

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease. Molecular characterization of AD shows an underlying inflammation with tissue infiltration of T helper (TH ) 2 cells and increased IL-4 and IL-13. The multifaceted roles of IL-4 and IL-13 in allergic disease development make IL-4Rα an attractive target for treatment strategies, and a neutralizing monoclonal antibody which antagonizes the effects of both IL-4 and IL-13 by blocking the interaction site found in the IL-4 receptor subunit α (IL-4Rα) has been successfully used to treat patients with moderate-to-severe AD. To elucidate the effects of IL-4Rα blockade on the cellular level, we used flow cytometry to examine cytokine production after antigen stimulation in human T cells from patients with AD (n = 12) and healthy controls (n = 6). The cells were stimulated with and without a neutralizing monoclonal antibody against IL-4Rα. Our results indicate that blocking IL-4Rα prohibits IL-4 signalling and IL-13 signalling and thereby TH 2 differentiation followed by an upregulation of interferon-γ-producing cells.


Assuntos
Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Subunidade alfa de Receptor de Interleucina-4/antagonistas & inibidores , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Adulto , Biomarcadores , Citocinas/metabolismo , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Medicine (Baltimore) ; 98(50): e18300, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852109

RESUMO

RATIONALE: Kimura disease (KD) is a rare, chronic inflammatory disorder characterized by subcutaneous granuloma in the head and neck region, as well as increased eosinophil counts and high serum immunoglobulin E (IgE) levels. Kimura disease is suspected to be an IgE-mediated disease, associated with an allergic response, in which antigen-specific B cells are stimulated to undergo specific IgE class switching with disease-specific CD4+ T (Th) cells help. Thus, exploration of the Th cells in affected tissues with KD is a highly promising field of the investigation. However, there have been no reports with direct evidence to implicate Th cells in affected lesions with KD. Here we quantitatively demonstrate that CD4+ GATA3+ T cells and interleukin (IL)-4+ IgE+ c-kit+ mast cells prominently infiltrate in affected lesion with KD. PATIENT CONCERNS: A 56-year-old Japanese man who exhibited painless swelling in the left parotid region. DIAGNOSES: Diagnosis of KD was made based on characteristic histopathologic findings, in conjunction with peripheral eosinophilia and elevated serum IgE levels. INTERVENTIONS: The patient underwent corticosteroid therapy and had been followed for 2 years. OUTCOMES: We report a rare case of KD of the parotid region in a 56-year-old man, followed by corticosteroid therapy for 2 years. The mass decreased in size and skin itchiness decreased after therapy. He was discharged without any complications. Furthermore, we quantitatively demonstrate the dominance of CD4+ GATA3+ T cells in affected tissues of KD and detect IL-4+ IgE+ c-kit+ mast cells in lesions by multicolor staining approaches. LESSONS: The findings from this case suggest that peripheral blood eosinophilia might serve as a marker of recurrent disease, long-term follow-up is necessary due to the possibility of recurrent. Interactions among expanded IgE+ B cells, CD4+ GATA3+ T cells, eosinophils, and activated mast cells might play a critical role in the pathogenesis of KD.


Assuntos
Hiperplasia Angiolinfoide com Eosinofilia/imunologia , Linfócitos B/imunologia , Eosinófilos/imunologia , Imunoglobulina E/sangue , Mastócitos/imunologia , Hiperplasia Angiolinfoide com Eosinofilia/sangue , Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico , Linfócitos B/patologia , Biópsia , Eosinófilos/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Mastócitos/patologia , Pessoa de Meia-Idade
5.
Zhonghua Nei Ke Za Zhi ; 58(11): 826-828, 2019 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-31665859

RESUMO

This study aims to explore the diagnostic value of specific immunoglobulin E (sIgE) and specific immunoglobulin G (sIgG) of Aspergillus fumigatus in the diagnosis of allergic broncho-pulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS). A total of 17 ABPA patients and 14 SAFS patients were enrolled. The levels of sIgG [2 294.00 (1 527.00, 14 170.00) U/ml vs. 972.60 (650.90, 1 792.00) U/ml] and sIgE [8.77 (1.64, 16.85) kU/L vs. 1.04 (0.70, 2.05) kU/L] in ABPA patients were significantly higher than those in SAFS patients (P<0.05). Aspergillus fumigatus sIgG was strongly correlated with Aspergillus fumigatus sIgE (r(s)=0.797, P<0.001) in ABPA patients. When combined with Aspergillus fumigatus sIgG (>1 000.00 U/mL) and Aspergillus fumigatus sIgE (>1.00 kU/L), the sensitivity was 82.3% and specificity 78.6% for the differential diagnosis of ABPA and SAFS. It demonstrates the diagnostic value of Aspergillus fumigatus sIgG and sIgE.


Assuntos
Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergillus fumigatus/isolamento & purificação , Asma/complicações , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Anticorpos Antifúngicos/imunologia , Aspergilose Broncopulmonar Alérgica/sangue , Aspergilose Broncopulmonar Alérgica/imunologia , Aspergilose Broncopulmonar Alérgica/microbiologia , Aspergillus fumigatus/imunologia , Asma/sangue , Asma/diagnóstico , Humanos , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Índice de Gravidade de Doença
6.
Arerugi ; 68(9): 1141-1147, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31723111

RESUMO

We present a case of early childhood-onset pork-cat syndrome possibly due to sensitization by both cats and dogs. A 6-year-old girl was referred to our hospital because of repetitive episodes of urticaria when she consumed pork meat. The patient lived with a dog and the ground floor of her house was a veterinary clinic run by her veterinarian parents. Blood tests demonstrated high specific IgE (≥50UA/ml) against cat dander, dog dander, pork, Sus s 1, Fel d 2, Can f 1, Can f 2, and Can f 3. The skin prick test was positive for raw pork and beef. Western blotting analysis detected hot spots on 67-kDa proteins in pork meat and cat dander extract. Cross-reactivity between these two proteins was confirmed by an inhibition test. Furthermore, crossreactivity between pork meat and dog dander extract was also noted. Taken together, the diagnosis of porkcat syndrome was made, and both cats and dogs were suggested to have led to the sensitization. The patient was advised to only eat well-cooked pork, and has been followed thereafter without additional reactions. The previously reported cases of this syndrome developed during adolescence and young adulthood because a considerable period from the sensitization to the development cross-reactivity with pork meat is required. To our best knowledge, this is the youngest reported case of pork-cat syndrome among English and Japanese literatures. The nomenclature of this syndrome as pet animal-meat syndrome improves the understanding of the underlying pathogenesis of cross-reactivity between animal albumins and meat albumins.


Assuntos
Hipersensibilidade Alimentar/imunologia , Carne Vermelha , Alérgenos , Animais , Gatos , Bovinos , Criança , Reações Cruzadas , Cães , Feminino , Humanos , Imunoglobulina E/sangue , Testes Cutâneos , Suínos , Adulto Jovem
7.
An Bras Dermatol ; 94(5): 549-552, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777355

RESUMO

BACKGROUND: Nipple eczema is a less common presentation of atopic dermatitis. No studies in the literature have correlated nipple eczema in pregnancy as a manifestation of atopic dermatitis. OBJECTIVE: To evaluate whether nipple eczema presenting in pregnancy is a manifestation of atopic dermatitis. METHODS: This was a prospective observational study including 100 women who presented with nipple eczema for the first time during pregnancy. The exclusion criteria were any patient with previous history of nipple eczema, those already on oral or topical treatment for atopic dermatitis or nipple eczema, and other disorders mimicking eczema. Patients were divided into two groups ‒ nipple eczema with atopic dermatitis and without atopic dermatitis. Demographic data, clinical features, total leukocyte count, differential leukocyte count, absolute eosinophil counts, and serum IgE levels were compared between the two groups to detect association between nipple eczema in pregnancy and atopic dermatitis. RESULTS: Out of 100 patients, 39 were diagnosed with atopic dermatitis, whereas 61 were ruled out to have any features suggestive of atopic dermatitis. There were no statistically significant differences in mean age, mean duration of symptoms, and serum IgE levels. In patients with atopic dermatitis, bilateral symptoms were noted more commonly than in patients without the disease, but this was statistically insignificant. STUDY LIMITATIONS: Lack of long term follow-up and no large studies in literature to compare results. CONCLUSION: Nipple eczema in pregnancy follows a similar pattern as in other age groups. The clinical profile of patients is similar in cases with and without atopic dermatitis.


Assuntos
Doenças Mamárias/patologia , Dermatite Atópica/patologia , Eczema/patologia , Mamilos/patologia , Complicações na Gravidez/patologia , Adulto , Doenças Mamárias/sangue , Doenças Mamárias/diagnóstico , Dermatite Atópica/sangue , Dermatite Atópica/diagnóstico , Eczema/sangue , Eczema/diagnóstico , Feminino , Humanos , Imunoglobulina E/sangue , Índia , Contagem de Leucócitos , Neutrófilos , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/diagnóstico , Trimestres da Gravidez , Estudos Prospectivos
8.
Int Arch Allergy Immunol ; 180(4): 264-273, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31597156

RESUMO

BACKGROUND: Adding baked food into the diets of patients with cow's milk allergy (MA) and hen's egg allergy (EA) has several benefits. OBJECTIVE: We aimed to determine baked and unbaked food tolerance and evaluate the effectiveness of laboratory findings on the prediction of baked and unbaked food tolerance in patients with MA and EA. METHODS: Clinical outcomes of the patients with MA and EA who had been exposed to oral food challenge with baked food were retrospectively analyzed. RESULTS: Ninety-one patients were evaluated. The median age of the study group was 22 months. Forty-nine and 42 patients had IgE-mediated MA and EA, respectively. While all patients with EA tolerated baked egg, 24.5% patients with MA could not tolerate baked cow's milk (BM). In patients with MA, BM tolerance showed negative association with milk-specific IgE, skin prick test (SPT), and prick-to-prick test (PTP), and the PTP was the most significant parameter (sensitivity 83.8%, specificity 91.7% for PTP ≤7 mm). Negative association was seen between milk-specific IgE, SPT, PTP, and unbaked milk (UBM) tolerance, and PTP was the most significant parameter (sensitivity 100%, specificity 55% for PTP ≤4 mm). In patients with EA, at the end of 6 months of baked hen's egg (BE) consumption, scrambled egg tolerance showed negative association with egg white-specific IgE level, egg white SPT and PTP. Egg white PTP was the most significant parameter (sensitivity 82.4%, specificity 96.0% for PTP ≤5 mm). CONCLUSION: Specific-IgE, SPT, and PTP should be kept in mind as parameters that can be used to predict tolerance to BM and BE for patients with MA and EA.


Assuntos
Alérgenos/administração & dosagem , Culinária/métodos , Dessensibilização Imunológica/métodos , Dieta/métodos , Hipersensibilidade a Ovo/patologia , Hipersensibilidade a Leite/patologia , Animais , Galinhas , Criança , Pré-Escolar , Ovos/efeitos adversos , Eosinófilos/imunologia , Feminino , Humanos , Tolerância Imunológica/imunologia , Imunoglobulina E/sangue , Lactente , Masculino , Leite/efeitos adversos
9.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3763-3772, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602951

RESUMO

The detection of drug-induced anaphylactoid reactions remains a global challenge,still lacking mature and reliable animal models or test methods. Therefore,the purpose of this paper is to explore and establish the test methods and evaluation standards for anaphylactoid reactions that apply to injection drugs. Based on the anaphylactoid reaction symptoms of mice induced by intravenous injection drugs C48/40 and Tween 80,a list of systemic anaphylactoid reaction symptoms in mice was sorted out and an evaluation standard of anaphylactoid reactions symptoms was established by applying symptom intensity coefficient K( that can represent these verity of anaphylactoid reaction symptoms) and its calculation formula Accordingly,histamine,tryptase,and Ig E were selected as blood indicators of anaphylactoid reactions,so that a test method combining symptoms evaluation and blood makers detection was established.This test method could be used to evaluate the characteristics of anaphylactoid reactions: coefficient K,blood histamine levels were highly and positively correlated with C48/80 and Tween 80 dose; The log value of histamine was highly and positively correlated with K; tryptase level may rise,or remain steady,or drop,possibly associated with the characteristics of the tested object and time for blood taking; and Ig E level would drop or remain steady,but it would not rise,which can be clearly distinguished from type I allergic reactions. On this basis,tiohexol,iopromide,paclitaxel,Xuesaitong Injection,Shuanghuanglian Injection and Shengmai Injection were used to investigate the applicability. The testing results showed a high degree of consistency with the actual clinical situation. The results suggest that the method of systemic anaphylaxis test in mice has high sensitivity,specificity and good consistency with clinical practice.It is suggested to be further validated and popularized.


Assuntos
Anafilaxia/induzido quimicamente , Anafilaxia/diagnóstico , Modelos Animais de Doenças , Animais , Medicamentos de Ervas Chinesas/toxicidade , Histamina/sangue , Imunoglobulina E/sangue , Injeções Intravenosas , Camundongos , Choque/induzido quimicamente , Choque/diagnóstico , Testes de Toxicidade , Triptases/sangue
10.
N Engl J Med ; 381(14): 1321-1332, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31577874

RESUMO

BACKGROUND: In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose-response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H1-antihistamines at approved or increased doses, alone or in combination with H2-antihistamines or leukotriene-receptor antagonists. METHODS: In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose-response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial. RESULTS: A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose-response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged. CONCLUSIONS: A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332.).


Assuntos
Antialérgicos/administração & dosagem , Anticorpos Anti-Idiotípicos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Omalizumab/administração & dosagem , Urticária/tratamento farmacológico , Adulto , Idoso , Antialérgicos/efeitos adversos , Anticorpos Anti-Idiotípicos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Doença Crônica , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Omalizumab/efeitos adversos , Gravidade do Paciente , Indução de Remissão , Urticária/imunologia , Adulto Jovem
11.
Ann Agric Environ Med ; 26(3): 439-444, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31559800

RESUMO

INTRODUCTION AND OBJECTIVE: An important role in the pathogenesis of asthma in children is played by individual parameters and environmental factors, in particular, those related to the place of residence. The aim of this study was to assess the impact of the living environment on the basic demographic and clinical parameters of preschool children with IgE-dependent asthma. MATERIAL AND METHODS: 176 children (126 from urban and 52 from rural areas) aged 5.22±0.34 years, with newly-diagnosed IgE-dependent asthma, hospitalised at the Clinic for Lung Diseases and Paediatric Rheumatology of the Prof. Antoni Gebala Children's Hospital of Lublin, were qualified for the study. Medical documentation of the children was analysed, including the implementation of vaccinations. Due to the clinical form of the disease, patients were separated into groups with mild, moderate and severe asthma. RESULTS: No statistically significant differentiation was observed between age and current body weight and height of the children. Similarly, gender and the clinical form of asthma were not significantly correlated with the place of residence. Children with asthma, at the time of exacerbation symptoms of the disease, living in a city, significantly more often (p <0.05) were treated with antibiotics in the hospital during hospitalization, while the value of OR (5.08) indicated that the rural environment enforces more frequent use of OGCs during asthma exacerbation therapy. In children from the urban environment, there was a significant correlation between the current body weight and serum calcium concentration, as well as a negative statistically significant correlation between the current body weight and serum selenium concentration. CONCLUSIONS: Residence does not determine the clinical course of IgE-dependent asthma in preschool children.


Assuntos
Asma/diagnóstico , Meio Ambiente , Habitação , Imunoglobulina E/sangue , Asma/sangue , Asma/imunologia , Asma/terapia , Peso Corporal , Cálcio/sangue , Pré-Escolar , Demografia , Feminino , Humanos , Masculino , Selênio/sangue
12.
Orv Hetil ; 160(38): 1514-1518, 2019 Sep.
Artigo em Húngaro | MEDLINE | ID: mdl-31537093

RESUMO

Immunglobulin E (IgE)-based, irregularly recurring, severe anaphylactic reactions occurred in a 50-year-old European white male patient suffering also from Crohn's disease. On the base of immunologic laboratory tests concerning the mechanism of the phenomenon, the idea arose whether molecules derived for certain microbial derivatives could enter the blood circulation via the damaged bowel walls in the patient with Crohn's disease and they might act as allergens. The microbial analysis diagnosed atypical Staphylococcus in the stool. The serum level of IgE was very high. The concomitant use of targeted antibiotics and anti-allergy and immunosuppressive agents resulted in a complete remission during a couple of months. Not only Crohn's disease has improved, but also the total serum IgE level has decreased significantly, and the unpredictable anaphylactic attacks have been completely eliminated. In Crohn's disease, the anaphylactic complications induced by atypical microbial allergens (e.g., derivatives of Staphylococcus) can be effectively treated after the recognition of this pathological mechanism. This is the first description of such a pathologic state. Orv Hetil. 2019; 160(38): 1514-1518.


Assuntos
Anafilaxia/tratamento farmacológico , Antialérgicos/uso terapêutico , Antibacterianos/uso terapêutico , Doença de Crohn/complicações , Imunoglobulina E/sangue , Imunossupressores/uso terapêutico , Staphylococcus , Anafilaxia/diagnóstico , Anafilaxia/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento
13.
PLoS Negl Trop Dis ; 13(9): e0007687, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31513587

RESUMO

Lymphatic filariasis (LF), a morbid disease caused by the tissue-invasive nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori, affects millions of people worldwide. Global eradication efforts have significantly reduced worldwide prevalence, but complete elimination has been hampered by limitations of current anti-filarial drugs and the lack of a vaccine. The goal of this study was to evaluate B. malayi intestinal UDP-glucuronosyltransferase (Bm-UGT) as a potential therapeutic target. To evaluate whether Bm-UGT is essential for adult filarial worms, we inhibited its expression using siRNA. This resulted in a 75% knockdown of Bm-ugt mRNA for 6 days and almost complete suppression of detectable Bm-UGT by immunoblot. Reduction in Bm-UGT expression resulted in decreased worm motility for 6 days, 70% reduction in microfilaria release from adult worms, and significant reduction in adult worm metabolism as detected by MTT assays. Because prior allergic-sensitization to a filarial antigen would be a contraindication for its use as a vaccine candidate, we tested plasma from infected and endemic normal populations for Bm-UGT-specific IgE using a luciferase immunoprecipitation assay. All samples (n = 35) tested negative. We then tested two commercially available medicines known to be broad inhibitors of UGTs, sulfinpyrazone and probenecid, for in vitro activity against B. malayi. There were marked macrofilaricidal effects at concentrations achievable in humans and very little effect on microfilariae. In addition, we observed that probenecid and sulfinpyrazone exhibit a synergistic macrofilaricidal effect when used in combination with albendazole. The results of this study demonstrate that Bm-UGT is an essential protein for adult worm survival. Lack of prior IgE sensitization in infected and endemic populations suggest it may be a feasible vaccine candidate. The finding that sulfinpyrazone and probenecid have in vitro effects against adult B. malayi worms suggests that these medications have promise as potential macrofilaricides in humans.


Assuntos
Brugia Malayi/efeitos dos fármacos , Brugia Malayi/enzimologia , Glucuronosiltransferase/metabolismo , Albendazol/farmacologia , Animais , Antígenos de Helmintos/sangue , Brugia Malayi/imunologia , Brugia Malayi/metabolismo , Quimioterapia Combinada , Filariose Linfática/tratamento farmacológico , Filariose Linfática/prevenção & controle , Feminino , Filaricidas/farmacologia , Glucuronosiltransferase/antagonistas & inibidores , Glucuronosiltransferase/genética , Humanos , Imunoglobulina E/sangue , Intestinos/enzimologia , Microfilárias/efeitos dos fármacos , Movimento , Probenecid/farmacologia , RNA Interferente Pequeno , Sulfimpirazona/farmacologia
14.
Lancet ; 394(10207): 1437-1449, 2019 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-31522849

RESUMO

BACKGROUND: Dietary avoidance is recommended for peanut allergies. We evaluated the sustained effects of peanut allergy oral immunotherapy (OIT) in a randomised long-term study in adults and children. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 study, we enrolled participants at the Sean N Parker Center for Allergy and Asthma Research at Stanford University (Stanford, CA, USA) with peanut allergy aged 7-55 years with a positive result from a double-blind, placebo-controlled, food challenge (DBPCFC; ≤500 mg of peanut protein), a positive skin-prick test (SPT) result (≥5 mm wheal diameter above the negative control), and peanut-specific immunoglobulin (Ig)E concentration of more than 4 kU/L. Participants were randomly assigned (2·4:1·4:1) in a two-by-two block design via a computerised system to be built up and maintained on 4000 mg peanut protein through to week 104 then discontinued on peanut (peanut-0 group), to be built up and maintained on 4000 mg peanut protein through to week 104 then to ingest 300 mg peanut protein daily (peanut-300 group) for 52 weeks, or to receive oat flour (placebo group). DBPCFCs to 4000 mg peanut protein were done at baseline and weeks 104, 117, 130, 143, and 156. The pharmacist assigned treatment on the basis of a randomised computer list. Peanut or placebo (oat) flour was administered orally and participants and the study team were masked throughout by use of oat flour that was similar in look and feel to the peanut flour and nose clips, as tolerated, to mask taste. The statistician was also masked. The primary endpoint was the proportion of participants who passed DBPCFCs to a cumulative dose of 4000 mg at both 104 and 117 weeks. The primary efficacy analysis was done in the intention-to-treat population. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02103270. FINDINGS: Between April 15, 2014, and March 2, 2016, of 152 individuals assessed, we enrolled 120 participants, who were randomly assigned to the peanut-0 (n=60), peanut-300 (n=35), and placebo groups (n=25). 21 (35%) of peanut-0 group participants and one (4%) placebo group participant passed the 4000 mg challenge at both 104 and 117 weeks (odds ratio [OR] 12·7, 95% CI 1·8-554·8; p=0·0024). Over the entire study, the most common adverse events were mild gastrointestinal symptoms, which were seen in 90 of 120 patients (50/60 in the peanut-0 group, 29/35 in the peanut-300 group, and 11/25 in the placebo group) and skin disorders, which were seen in 50/120 patients (26/60 in the peanut-0 group, 15/35 in the peanut-300 group, and 9/25 in the placebo group). Adverse events decreased over time in all groups. Two participants in the peanut groups had serious adverse events during the 3-year study. In the peanut-0 group, in which eight (13%) of 60 participants passed DBPCFCs at week 156, higher baseline peanut-specific IgG4 to IgE ratio and lower Ara h 2 IgE and basophil activation responses were associated with sustained unresponsiveness. No treatment-related deaths occurred. INTERPRETATION: Our study suggests that peanut OIT could desensitise individuals with peanut allergy to 4000 mg peanut protein but discontinuation, or even reduction to 300 mg daily, could increase the likelihood of regaining clinical reactivity to peanut. Since baseline blood tests correlated with week 117 treatment outcomes, this study might aid in optimal patient selection for this therapy. FUNDING: National Institute of Allergy and Infectious Diseases.


Assuntos
Arachis , Dessensibilização Imunológica/métodos , Hipersensibilidade a Amendoim/terapia , Proteínas de Plantas/administração & dosagem , Administração Oral , Adolescente , Criança , Dessensibilização Imunológica/efeitos adversos , Método Duplo-Cego , Feminino , Gastroenteropatias/etiologia , Humanos , Imunoglobulina E/sangue , Masculino , Hipersensibilidade a Amendoim/diagnóstico , Hipersensibilidade a Amendoim/imunologia , Proteínas de Plantas/efeitos adversos , Testes Cutâneos , Resultado do Tratamento
15.
Int J Med Sci ; 16(8): 1116-1122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523174

RESUMO

This study investigated the anti-allergic effect of Poncirus trifoliata (L.) Raf. (PT) on human keratinocytic HaCaT cells in vitro and on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like lesions in vivo. The release of TARC, MCP-1, IL-6 and IL-8 is increased by IFN-γ and TNF-α in HaCaT cells, and PT extract suppressed the increased production of TARC, MCP-1, IL-6, and IL-8. PT extract recovered the expression of filaggrin decreased by IFN-γ and TNF-α. in vivo experiment, PT administration decreased the skin severity score, thickening of the epidermis, movement of inflammatory cells into the dermis, and serum IgE level as compared to DNCB treatment. Moreover, the decrease of filaggrin and loricrin induced by DNCB treatment was recovered by PT administration. The levels of IL-4, IL-5, IL-13 and eotaxin in mouse splenocytes increased after treatment with concanavalin A, and the secretions of IL-4, IL-5, IL-13 and eotaxin were lower in the PT-treated group than in the DNCB group. These findings may indicate that PT is useful in drug development for the treatment of AD.


Assuntos
Dermatite Atópica/tratamento farmacológico , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Extratos Vegetais/farmacologia , Poncirus/química , Animais , Linhagem Celular , Quimiocina CCL11/metabolismo , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/patologia , Dinitroclorobenzeno/toxicidade , Feminino , Humanos , Imunoglobulina E/sangue , Interferon gama/farmacologia , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos , Proteínas S100/metabolismo , Baço/citologia , Baço/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
16.
Int Arch Allergy Immunol ; 180(4): 250-254, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31522183

RESUMO

INTRODUCTION: Chronic spontaneous urticaria (CSU) in childhood affects the quality of life of the patient and may be associated with other autoimmune diseases. The aim of this study was to investigate the association of autoimmune diseases with CSU in children. METHODS: In a 3-year period, from 2015 to 2018, forty-nine children were diagnosed with CSU and monitored in the Outpatient Pediatric Allergy Clinic of the University Hospital of Ioannina in Northwestern Greece. The comorbidity with other autoimmune diseases was investigated in this population by autoantibody evaluation. RESULTS: Of the 49 children with CSU, 1 had autoantibodies for celiac disease (CD), which was confirmed by duodenal biopsy via gastroscopy. Four children had high serum levels of anti-thyroid peroxidase antibodies but normal thyroid function. No other specific autoantibodies were detected. CONCLUSION: The prevalence of autoimmune diseases among our children with CSU was low. Nevertheless, we think it is important to test children with CSU for other autoimmune diseases. CD can be diagnosed in children with CSU even in the absence of other indicative signs.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/imunologia , Doença Celíaca/sangue , Imunoglobulina E/sangue , Adolescente , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Criança , Pré-Escolar , /patologia , Comorbidade , Feminino , Humanos , Lactente , Masculino , Mastócitos/imunologia
18.
Orv Hetil ; 160(33): 1311-1318, 2019 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-31401863

RESUMO

Introduction and aim: The aim of our research is to evaluate and compare commonly performed diagnostic tests, and to examine the psychological disorders induced by this food allergy. Children with symptoms suggesting cow's milk protein allergy were included in this study (n = 47). Blood and saliva samples were collected from the participants. Parents were asked to fill in a questionnaire constructed by the research team (containing the DSM-5 symptoms checklist about attention deficit hyperactivity disorder). Method: One of the most widely used diagnostic tool is the skin allergy test, which was performed in 47 subjects (n = 47, mean age: 7.36 years); only 2 children showed positive test result for cow's milk. Lymphocyte transformation test was observed to be positive in 8 children (17%), 4 subjects demonstrated questionable results. In our sub-study about psychological symptoms (n = 43, mean age: 7.88 years), the score was according to the attention deficit hyperactivity disorder symptom checklist before the diet (6.88, SD: 4.43) and showed significant decrease after 3 months of the elimination diet (4.48, SD: 3.69, p = 0.001). Scores of children with sleep disorder (10.62, SD: 4.23) also represented a significant reduction after 3 months of the diet (6.69, SD: 4.59, p = 0.009). Salivary cortisol levels did not show significant changes before and after elimination diet. Results: According to our data, skin allergy testing and lymphocyte transformation test are not reliable diagnostic tools for establishing the diagnosis. Conclusion: We conclude that a significant improvement in clinical symptoms can only be achieved with a strict elimination diet. Orv Hetil. 2019; 160(33): 1311-1318.


Assuntos
Alérgenos/imunologia , Imunoglobulina E/imunologia , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/imunologia , Proteínas do Leite/efeitos adversos , Animais , Bovinos , Criança , Pré-Escolar , Feminino , Hipersensibilidade Alimentar , Humanos , Imunoglobulina E/sangue , Lactente , Recém-Nascido , Masculino , Proteínas do Leite/imunologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Testes Cutâneos/métodos
19.
Arerugi ; 68(7): 851-856, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31406081

RESUMO

BACKGROUND: The present study aimed to assess the safety of a three-level stepwise oral food challenge (OFC) in patients with peanut allergy. METHODS: This retrospective analysis reviewed laboratory test results and food allergy histories (obtained from medical records) of participants who underwent OFC using peanut butter for the first time at Miyagi Children's Hospital between January 2015 and December 2017. Total food dose was classified as follows: step 1, 0.1 g peanut butter; step 2, 0.5g peanut butter; and step 3, 3g peanut butter. RESULTS: A total of 114 participants were included. OFC-positive rates were 52% (step 1), 35% (step 2), and 20% (step 3). Of the 41 OFC-positive participants, 1 required an intramuscular adrenaline injection during step 3. Peanut allergy history rates and peanut- and Ara h 2-specific immunoglobulin E (sIgE) titers were significantly higher during the low-dose step. CONCLUSION: The three-level stepwise OFC with peanut butter is safe for patients with peanut allergy, as indicated by peanut- and Ara h 2-sIgE titers.


Assuntos
Alimentos , Hipersensibilidade a Amendoim/diagnóstico , Albuminas 2S de Plantas/imunologia , Antígenos de Plantas/imunologia , Arachis , Criança , Glicoproteínas/imunologia , Humanos , Imunoglobulina E/sangue , Estudos Retrospectivos
20.
Molecules ; 24(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426284

RESUMO

Allergic disease is one of the most important and common health problems worldwide. We have previously demonstrated that a fig leaf-derived lactic acid bacterium Lactobacillus (Lb.) paracasei IJH-SONE68 produces a novel exopolysaccharide (EPS). Furthermore, we have shown that the EPS inhibits the catalytic activity of hyaluronidase (EC 3.2.1.36) promoting inflammatory reactions. To evaluate the anti-allergy and anti-inflammatory effects of the EPS, in the present study, we employed the picryl-chloride-induced delayed-type (type IV) allergy model mice, which is used to evaluate the contact dermatitis. Oral administration of the EPS was observed to reduce the ear swelling in the model mice. We also observed that the overexpression of ear interleukin-4 (T helper (Th) 2 cytokine) mRNA and the increase in serum immunoglobulin E (IgE) are repressed. However, the expression of interferon-γ (Th1 cytokine) was not accelerated in all of the allergen-challenged model mice. The improvement may be responsible for the Th2 downregulation rather than the Th1 upregulation. In addition, the symptom of immediate-type (type I) allergy model mice was improved by oral administration of the IJH-SONE68 cell (data not shown). We can conclude that the IJH-SONE68-derived EPS is useful to improve the type I and IV allergies including atopic dermatitis.


Assuntos
Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Dermatite de Contato/prevenção & controle , Fármacos Dermatológicos/farmacologia , Lactobacillus paracasei/química , Polissacarídeos Bacterianos/farmacologia , Administração Oral , Alérgenos/imunologia , Alérgenos/metabolismo , Animais , Antialérgicos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Dermatite de Contato/etiologia , Dermatite de Contato/imunologia , Dermatite de Contato/patologia , Fármacos Dermatológicos/isolamento & purificação , Modelos Animais de Doenças , Orelha , Expressão Gênica/efeitos dos fármacos , Hialuronoglucosaminidase/antagonistas & inibidores , Hialuronoglucosaminidase/imunologia , Hialuronoglucosaminidase/metabolismo , Imunoglobulina E/sangue , Imunoglobulina E/genética , Interferon gama/genética , Interferon gama/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Lactobacillus paracasei/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Cloreto de Picrila/administração & dosagem , Polissacarídeos Bacterianos/isolamento & purificação , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
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