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1.
Curr Opin Allergy Clin Immunol ; 19(5): 439-446, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31169597

RESUMO

PURPOSE OF REVIEW: The use of biologicals as therapeutic agents in oncology and other inflammatory diseases has dramatically increased during the last years. Due to their biological nature and inherent immunological activity, they are able to induce important adverse events, such as cytokine release reactions (rapid release of proinflammatory cytokines), serum sickness disease, and immediate or delayed hypersensitivity reactions, including anaphylaxis. The aim of the current article is to review the state of the art of anaphylaxis because of biological agents. RECENT FINDINGS: Different phenotypes, and potential underlying endotypes, have been described in anaphylactic reactions to biologicals. There seems to be a spectrum from type 1 reactions (IgE or non-IgE-mediated) to cytokine release reactions, with some reactions falling in between both. Management should be directed according to such phenotypes. SUMMARY: There is ongoing research to further define immediate adverse reactions to biologicals and to find relevant biomarkers to aid in their diagnosis. Such information will serve in defining their immediate and long term management.

4.
Mol Genet Metab ; 126(3): 250-258, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30642748

RESUMO

AIM: To perform a deep phenotype characterisation in a pedigree of 3 siblings with Leigh syndrome and compound heterozygous NDUFAF6 mutations. METHOD: A multi-gene panel of childhood-onset basal ganglia neurodegeneration inherited conditions was analysed followed by functional studies in fibroblasts. RESULTS: Three siblings developed gait dystonia in infancy followed by rapid progression to generalised dystonia and psychomotor regression. Brain magnetic resonance showed symmetric and bilateral cytotoxic lesions in the putamen and proliferation of the lenticular-striate arteries, latter spreading to the caudate and progressing to cavitation and volume loss. We identified a frameshift novel change (c.554_558delTTCTT; p.Tyr187AsnfsTer65) and a pathogenic missense change (c.371T>C; p.Ile124Thr) in the NDUFAF6 gene, which segregated with an autosomal recessive inheritance within the family. Patient mutations were associated with the absence of the NDUFAF6 protein and reduced activity and assembly of mature complex I in fibroblasts. By functional complementation assay, the mutant phenotype was rescued by the canonical version of the NDUFAF6. A literature review of 14 NDUFAF6 patients showed a consistent phenotype of an early childhood insidious onset neurological regression with prominent dystonia associated with basal ganglia degeneration and long survival. INTERPRETATION: NDUFAF6-related Leigh syndrome is a relevant cause of childhood onset dystonia and isolated bilateral striatal necrosis. By genetic complementation, we could demonstrate the pathogenicity of novel genetic variants in NDUFAF6.

5.
Front Immunol ; 9: 1584, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30065721

RESUMO

Allergic diseases, such as respiratory, cutaneous, and food allergy, have dramatically increased in prevalence over the last few decades. Recent research points to a central role of the microbiome, which is highly influenced by multiple environmental and dietary factors. It is well established that the microbiome can modulate the immune response, from cellular development to organ and tissue formation exerting its effects through multiple interactions with both the innate and acquired branches of the immune system. It has been described at some extent changes in environment and nutrition produce dysbiosis in the gut but also in the skin, and lung microbiome, inducing qualitative and quantitative changes in composition and metabolic activity. Here, we review the potential role of the skin, respiratory, and gastrointestinal tract (GIT) microbiomes in allergic diseases. In the GIT, the microbiome has been proven to be important in developing either effector or tolerant responses to different antigens by balancing the activities of Th1 and Th2 cells. In the lung, the microbiome may play a role in driving asthma endotype polarization, by adjusting the balance between Th2 and Th17 patterns. Bacterial dysbiosis is associated with chronic inflammatory disorders of the skin, such as atopic dermatitis and psoriasis. Thus, the microbiome can be considered a therapeutical target for treating inflammatory diseases, such as allergy. Despite some limitations, interventions with probiotics, prebiotics, and/or synbiotics seem promising for the development of a preventive therapy by restoring altered microbiome functionality, or as an adjuvant in specific immunotherapy.

6.
Front Immunol ; 8: 846, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28798744

RESUMO

Anaphylaxis is the most severe form of allergic reaction, resulting from the effect of mediators and chemotactic substances released by activated cells. Mast cells and basophils are considered key players in IgE-mediated human anaphylaxis. Beyond IgE-mediated activation of mast cells/basophils, further mechanisms are involved in the occurrence of anaphylaxis. New insights into the potential relevance of pathways other than mast cell and basophil degranulation have been unraveled, such as the activation of the contact and the coagulation systems. Mast cell heparin released upon activation provides negatively charged surfaces for factor XII (FXII) binding and auto-activation. Activated FXII, the initiating serine protease in both the contact and the intrinsic coagulation system, activates factor XI and prekallikrein, respectively. FXII-mediated bradykinin (BK) formation has been proven in the human plasma of anaphylactic patients as well as in experimental models of anaphylaxis. Moreover, the severity of anaphylaxis is correlated with the increase in plasma heparin, BK formation and the intensity of contact system activation. FXII also activates plasminogen in the fibrinolysis system. Mast cell tryptase has been shown to participate in fibrinolysis through plasmin activation and by facilitating the degradation of fibrinogen. Some usual clinical manifestations in anaphylaxis, such as angioedema or hypotension, or other less common, such as metrorrhagia, may be explained by the direct effect of the activation of the coagulation and contact system driven by mast cell mediators.

10.
J Allergy Clin Immunol ; 135(4): 1031-43.e6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25240785

RESUMO

BACKGROUND: Anaphylaxis is an acute, potentially lethal, multisystem syndrome resulting from the sudden release of mast cell-derived mediators into the circulation. OBJECTIVES AND METHODS: We report here that a plasma protease cascade, the factor XII-driven contact system, critically contributes to the pathogenesis of anaphylaxis in both murine models and human subjects. RESULTS: Deficiency in or pharmacologic inhibition of factor XII, plasma kallikrein, high-molecular-weight kininogen, or the bradykinin B2 receptor, but not the B1 receptor, largely attenuated allergen/IgE-mediated mast cell hyperresponsiveness in mice. Reconstitutions of factor XII null mice with human factor XII restored susceptibility for allergen/IgE-mediated hypotension. Activated mast cells systemically released heparin, which provided a negatively charged surface for factor XII autoactivation. Activated factor XII generates plasma kallikrein, which proteolyzes kininogen, leading to the liberation of bradykinin. We evaluated the contact system in patients with anaphylaxis. In all 10 plasma samples immunoblotting revealed activation of factor XII, plasma kallikrein, and kininogen during the acute phase of anaphylaxis but not at basal conditions or in healthy control subjects. The severity of anaphylaxis was associated with mast cell degranulation, increased plasma heparin levels, the intensity of contact system activation, and bradykinin formation. CONCLUSIONS: In summary, the data collectively show a role of the contact system in patients with anaphylaxis and support the hypothesis that targeting bradykinin generation and signaling provides a novel and alternative treatment strategy for anaphylactic attacks.


Assuntos
Anafilaxia/imunologia , Anafilaxia/metabolismo , Fator XII/metabolismo , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Mastócitos/imunologia , Adulto , Idoso , Anafilaxia/complicações , Anafilaxia/genética , Animais , Biomarcadores , Bradicinina/metabolismo , Modelos Animais de Doenças , Fator XII/antagonistas & inibidores , Fator XII/genética , Feminino , Humanos , Hipersensibilidade/complicações , Hipersensibilidade/genética , Hipotensão/etiologia , Cininogênios/metabolismo , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Receptor B2 da Bradicinina/genética , Receptor B2 da Bradicinina/metabolismo , Transdução de Sinais , Fatores de Tempo , Adulto Jovem
11.
Case Rep Genet ; 2014: 517091, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25379297

RESUMO

Angelman syndrome (AS, OMIM 105830) is a neurogenetic disorder with firm clinical diagnostic guidelines, characterized by severe developmental delay and speech impairment, balanced and behavioral disturbance as well as microcephaly, seizures, and a characteristic electroencephalogram (EEG). The majority of AS cases (70%) are caused by a 15q11.2-q13 deletion on the maternally derived chromosome. The frequency of AS has been estimated to be between 1/10000 and 1/20000. Klinefelter syndrome (KS) occurs due to the presence of an extra X chromosome (karyotype 47,XXY). The main features in KS are small testes, hypergonadotropic hypogonadism, gynecomastia, learning difficulties, and infertility. We present what is, to our knowledge, the first case of a patient with both KS and AS due to a 15q11.2-q13 deletion on the maternally derived chromosome and an extra X chromosome of paternal origin. He showed dysmorphic features, axial hypotonia, and delayed acquisition of motor skills. Early diagnosis is essential for optimal treatment of AS children; this is one of the earliest diagnosed cases of AS probably due to the presence of two syndromes. Clinical findings in this patient here described may be helpful to identify any other cases and to evaluate recurrence risks in these families.

12.
Clin Transl Allergy ; 4: 28, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25250172

RESUMO

The knowledge on molecular allergy diagnosis is continuously evolving. It is now time for the clinician to integrate this knowledge and use it when needed to improve the accuracy of diagnosis and thus provide more precise therapeutic and avoidance measures. This review does not intend to comprehensively analyze all the available allergen molecules, but to provide some practical clues on use and interpretation of molecular allergy diagnosis. The potential role of component resolved diagnosis in circumstances such as the indication of allergen immunotherapy, pollen polysensitization, food allergy, latex allergy or anaphylaxis, is assessed. Interpreting the information provided by molecular allergy diagnosis needs a structured approach. It is necessary to evaluate single positivities and negativities, but also to appraise "the big picture" with perspective.

13.
Orphanet J Rare Dis ; 8: 92, 2013 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-23800320

RESUMO

BACKGROUND: Mucopolysaccharidosis type II (MPS II) is an inherited X-linked disease associated with a deficiency in the enzyme iduronate 2-sulfatase due to iduronate 2-sulfatase gene (IDS) mutations. Recent studies in MPS II carriers did not find clinical involvement, but these were mainly performed by anamnesis and patients' self-reported description of signs and symptoms. So although it is rare in heterozygous carriers, investigations in other types of inherited X-linked disorders suggest that some clinical manifestations may be a possibility. The aim of this study was to evaluate the clinical pattern in female carriers of MPS II and to determine whether clinical symptoms were associated with the X-chromosome inactivation (XCI) pattern and age. METHODS: Female carriers of MPS II were genetically identified by molecular analysis of IDS. The clinical evaluation protocol included pedigree analysis, a comprehensive anamnesis, complete physical examination, ophthalmological evaluation, brain-evoked auditory response, electrocardiogram, echocardiogram, pulmonary function tests, abdominal sonogram, skeletal survey, neurophysiological studies, blood cell counts and biochemistry, urine glycosaminoglycan (GAGs) quantification, karyotype and pattern of XCI. RESULTS: Ten women were included in the study. The mean age of the participants was 40.2 ± 13.1 years. Six carriers presented a skewed XCI pattern, 3 of whom (aged 38, 42 and 52 years) had increased levels of GAGs in the urine and showed typical MPS II clinical manifestations, such as skeletal anomalies, liver abnormalities, carpal tunnel syndrome, recurrent ear infection, hypoacusia and more frequent severe odontological problems without coarse facial features. CONCLUSIONS: This is the first study performing a comprehensive evaluation of heterozygous MPS II carriers. Our results provide evidence of possible progressive, age-dependent, mild clinical manifestations in MPS II female carriers with a skewed XCI pattern, most likely affecting the normal allele. Further comparative studies with systematized clinical examinations in larger age-stratified populations of MPS II female carriers are required.


Assuntos
Mucopolissacaridose II/patologia , Adulto , Estudos Transversais , Feminino , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/urina , Humanos , Iduronato Sulfatase/metabolismo , Pessoa de Meia-Idade , Mucopolissacaridose II/metabolismo , Mucopolissacaridose II/urina , Inativação do Cromossomo X/genética
14.
Int Arch Allergy Immunol ; 160(2): 192-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23018683

RESUMO

BACKGROUND: The diagnosis of anaphylaxis is based on clinical history since no reliable biological marker is currently available to confirm the diagnosis. OBJECTIVE: It was the aim of this study to determine sequential serum tryptase concentrations during anaphylaxis and to evaluate its potential as a diagnostic marker. METHODS: We performed a prospective study including patients with acute anaphylaxis (according to the National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network criteria) attending the emergency department. Demographic characteristics, anaphylactic triggers, specific risk factors, clinical characteristics and management of anaphylaxis were recorded. Serum tryptase was measured at 1-2 h (T1), 4-6 h (T2) and 12-24 h (T3) following onset of the episode and at basal conditions (TB). RESULTS: A total of 102 patients were included (63 females, mean age 47.4 ± 19.1 years). Tryptase concentration at T1 (19.3 ± 15.4 µg/l) was significantly higher than at T2, T3 and TB (all <11.4 µg/l; p < 0.0001). Importantly, tryptase was not raised in 36.3% of cases; furthermore, in 60.6% of these patients, no changes were observed in tryptase levels comparing T1 and TB (ΔT1-TB = 0). Tryptase was more frequently elevated in more severe anaphylaxis (p < 0.0001) and positively correlated with the grades of severity (p < 0.001, r = 0.49). Anaphylaxis was more severe and tryptase concentration higher when the causative agent was a drug compared to food, both at T1 (p = 0.045) and at TB (p = 0.019). Age and coronary risk factors were associated with more severe anaphylaxis (p = 0.001). CONCLUSION: Tryptase is a biomarker related to the severity of anaphylaxis. However, since its concentration remains unaltered in a considerable number of patients during acute anaphylaxis, there is a need for more reliable diagnostic biological tests.


Assuntos
Anafilaxia/sangue , Anafilaxia/diagnóstico , Triptases/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Respiration ; 83(3): 239-44, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21832821

RESUMO

BACKGROUND: Exhaled nitric oxide (ENO) is used as a marker of airway inflammation. Factors such as spirometric maneuvers (SPM), ß(2)-agonists, or tobacco smoking have been postulated to affect ENO measurements. Guidelines on measurement techniques have been published based on expert opinions. Nevertheless, there is no strong clinical evidence of many aspects because they have not been supported by research data. OBJECTIVES: The aim of this study was to evaluate the influence of performing a spirometry or receiving inhaled salbutamol on ENO readings. METHODS: One hundred forty-five adults and 62 children with allergic asthma were included with a mean age of 36 ± 13 years for adults and 13 ± 2 years for children. A control group comprised 30 healthy adults and 30 children with a mean age of 37 ± 14 years and 13 ± 2 years, respectively. ENO measurements were performed with a NIOX-MINO® electrochemical device. In 179 patients ENO was measured before and after performing SPM and in 88 patients before and 15 min after SPM plus 2 puffs of salbutamol (100 µg/puff). RESULTS: There were no significant differences in mean ENO levels before and after SPM or before and after SPM plus 2 puffs of inhaled salbutamol in adults or children (asthmatic or healthy). CONCLUSIONS: Levels of ENO are not significantly affected by SPM or salbutamol inhalation.


Assuntos
Albuterol/farmacologia , Asma/metabolismo , Broncodilatadores/farmacologia , Hipersensibilidade/metabolismo , Óxido Nítrico/análise , Administração por Inalação , Adolescente , Adulto , Idoso , Testes Respiratórios , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Espirometria , Adulto Jovem
16.
Clin Transl Allergy ; 1(1): 11, 2011 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-22409889

RESUMO

Demographic distribution of the population is progressively changing with the proportion of elderly persons increasing in most societies. This entails that there is a need to evaluate the impact of common diseases, such as asthma and other allergic conditions, in this age segment. Frailty, comorbidities and polymedication are some of the factors that condition management in geriatric patients. The objective of this review is to highlight the characteristics of allergic diseases in older age groups, from the influence of immunosenescence, to particular clinical implications and management issues, such as drug interactions or age-related side effects.

17.
Asian Pac J Allergy Immunol ; 28(4): 275-8, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21337912

RESUMO

BACKGROUND: Diagnosis of fruit sensitisation by skin prick test (SPT) is fast and easy to perform. Nevertheless, some fruit is not available throughout the year. Freezing aliquots of these fresh fruits to be defrosted would be a good solution to perform SPT at any time. OBJECTIVE: To compare the reproducibility of SPT with Rosaceae and Cucurbitaceae frozen fruit with fresh and commercial fruit extracts. METHODS: SPT with the following fruit were performed: apricot, cherry, strawberry, nectarine, Japanese medlar, peach, (peel and pulp), yellow and red plum, melon and watermelon. We compared fresh fruit, commercial extract and fruit which had been frozen at -18 degrees C. Results were read by planimetry (Inmunotek prick-film) after 15 minutes. RESULTS: The study group comprised 48 patients (9 males, 39 females) with a mean age of 31, 6 +/- 2.0 years. Concordance of positive and negative results was extremely high and significant in all cases. Correlation between frozen fruit and commercial extract, frozen fruit and fresh and commercial extract and fresh fruit was statistically significant in all cases except for strawberry. CONCLUSIONS: The use of frozen fruit is a valid method, as the performance of the SPT is similar to that of fresh fruit. This enables diagnostic procedures with seasonal fruit at any time of the year.


Assuntos
Alérgenos/metabolismo , Misturas Complexas/metabolismo , Hipersensibilidade Alimentar/diagnóstico , Frutas/metabolismo , Testes Cutâneos , Adulto , Alérgenos/química , Alérgenos/imunologia , Misturas Complexas/administração & dosagem , Misturas Complexas/química , Cucurbitaceae/imunologia , Interpretação Estatística de Dados , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/fisiopatologia , Congelamento , Frutas/imunologia , Humanos , Masculino , Reprodutibilidade dos Testes , Rosaceae/imunologia , Testes Cutâneos/métodos , Testes Cutâneos/normas
19.
Med Clin (Barc) ; 126(11): 424-30, 2006 Mar 25.
Artigo em Espanhol | MEDLINE | ID: mdl-16595088

RESUMO

Food allergy is a growing health issue; its prevalence has exponentially increased in the past years, and it is situated around 4-5% of the general population. Health professionals will frequently have to deal with the management of affected patients. Only a minor number of foods cause the majority of allergic reactions. In Spain, milk, egg and fish are the most frequent sensitizers in children with food allergy; in adults, fruits and nuts, followed by fish and sea-food are the main food allergens. Clinical manifestations range from mild cutaneous reactions to life-threatening anaphylaxis. Therefore, an accurate diagnosis is crucial, as well as a correct medical treatment of reactions. Furthermore, patients and care-givers should be instructed on allergen avoidance and on the use of emergency kits in case of accidental ingestion.


Assuntos
Hipersensibilidade Alimentar , Alérgenos/efeitos adversos , Alérgenos/imunologia , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/fisiopatologia , Humanos
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