RESUMO
Hymenoptera venom immunotherapy (HVI) is a long-term effective treatment to avoid new systemic reactions in patients with Hymenoptera allergy. The sting challenge test is considered the gold standard to confirm the tolerance. However, the use of this technique is not generalized in clinical practice, being the basophil activation test (BAT), which functionally explores allergen response, an alternative that does not entail any of the provocation risks associated with the sting challenge test. This study reviews the publications that used the BAT to follow up and evaluate the success of the HVI. Studies assessing the changes between a baseline BAT before the start and BATs performed between the starting and maintenance phases of the HVI were selected. Ten articles were found, comprising information from 167 patients, of which 29% used the sting challenge test. The studies concluded the importance of evaluating the responses with submaximal allergen concentrations, which reflect basophil sensitivity, to monitor the HVI using the BAT. It was also observed that changes in the maximum response (reactivity) could not reflect the clinical status of tolerance, particularly in the initial phases of HVI.
La inmunoterapia con veneno de himenópteros (IVH) es, a largo plazo, un tratamiento eficaz para evitar nuevas reacciones sistémicas en pacientes con alergia a este tipo de insectos. La prueba de repicadura controlada es el estudio de referencia para confirmar la tolerancia del individuo. Sin embargo, no se ha generalizado su indicación clínica, por lo que la prueba de activación de basófilos (TAB) resulta una buena alternativa, pues valora de manera funcional la respuesta al alérgeno y está exenta de los riesgos asociados con la provocación. En esta revisión se explora la utilidad de la TAB en el seguimiento y valoración del éxito de la IVH. Se seleccionaron estudios que evalúan los cambios entre una TAB basal y en otro momento de la fase de inicio o mantenimiento de la IVH. Se incluyeron 10 estudios con datos de 167 pacientes, de los que el 29% había tenido prueba de repicadura controlada. Para vigilar la eficacia de la IVH debe explorarse la respuesta del basófilo, con la determinación de las concentraciones submáximas del alérgeno, que reflejan la sensibilidad del basófilo. Los cambios en la respuesta máxima (reactividad) no pueden aportar información del estado de tolerancia, especialmente en las fases iniciales de la IVH.
Assuntos
Teste de Degranulação de Basófilos , Dessensibilização Imunológica , Humanos , Seguimentos , Basófilos , Tolerância ImunológicaRESUMO
Hookworms infect more that 400 million people and cause significant socio-economic burden on endemic countries. The lack of efficient vaccines and the emergence of anthelminthic drug resistance are of major concern. Free-living hookworm larvae infect their hosts via the skin and live as adult worms in the small intestine where they feed on host tissue and blood. Excretory/secretory (E/S) products, released by helminths as they migrate through their host, are thought to play a key role in facilitating infection and successful establishment of parasitism. However, E/S products can also elicit protective immune responses that might be harnessed for vaccine development. By performing Western blots with serum of Nippostrongylus brasiliensis (Nb) infected mice as a model for human hookworm infection, we identified a largely overlapping set of IgG1- and IgE-reactive antigens in E/S from infective L3 stage larvae. Mass spectrometry analysis led to the identification of a new protein family with 6 paralogues in the Nb genome which we termed Nb-LSA1 for "Nippostrongylus brasiliensis larval secreted protein 1". The recombinantly expressed 17 kDa family member Nb-LSA1a was recognized by antibodies in the serum of Nb immune mice. Immunization of mice with Nb-LSA1a in alum elicited a strong IgG1 response but no detectable antigen-specific IgE. Most importantly, immunized mice were largely protected against a challenge Nb infection. This effect was dependent on the presence of basophils and occurred before the parasites reached the intestine. Therefore, basophils appear to play a critical role for rapid control of infection with L3 stage larvae in mice immunized with a single secreted larval protein. A better understanding of basophil-mediated protective immunity and identification of potent larval antigens of human hookworms could help to develop promising vaccination strategies.
Assuntos
Antígenos de Helmintos , Basófilos , Ancylostomatoidea , Animais , Humanos , Imunoglobulina E , Imunoglobulina G , Larva , Camundongos , NippostrongylusRESUMO
Cancer is the second leading cause of death globally and its incidence and mortality are rapidly increasing worldwide. The dynamic interaction of immune cells and tumor cells determines the clinical outcome of cancer. Immunotherapy comes to the forefront of cancer treatments, resulting in impressive and durable responses but only in a fraction of patients. Thus, understanding the characteristics and profiles of immune cells in the tumor microenvironment (TME) is a necessary step to move forward in the design of new immunomodulatory strategies that can boost the immune system to fight cancer. Histamine produces a complex and fine-tuned regulation of the phenotype and functions of the different immune cells, participating in multiple regulatory responses of the innate and adaptive immunity. Considering the important actions of histamine-producing immune cells in the TME, in this review we first address the most important immunomodulatory roles of histamine and histamine receptors in the context of cancer development and progression. In addition, this review highlights the current progress and foundational developments in the field of cancer immunotherapy in combination with histamine and pharmacological compounds targeting histamine receptors.
Assuntos
Histamina/metabolismo , Neoplasias/metabolismo , Receptores Histamínicos/metabolismo , Microambiente Tumoral/imunologia , Imunidade Adaptativa/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Linfócitos B/imunologia , Linfócitos B/metabolismo , Basófilos/imunologia , Basófilos/metabolismo , Histamina/imunologia , Humanos , Imunidade Inata/imunologia , Imunoterapia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Mastócitos/imunologia , Mastócitos/metabolismo , Neoplasias/imunologia , Neoplasias/terapia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Receptores Histamínicos/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
INTRODUCTION: In many cases of drug allergy, it is necessary to do in vitro test, for several reasons. BAT (basophil activation test) is a very useful weapon in these cases. In many iv. or im. depot preparations, the culprit of the allergic reaction is an excipient, and not the main component. CASE REPORT: A 37-year-old male, suffering from a Klinefelter syndrome needed treatment with a preparation of undecanoate of testosterone (Reandron). With the last administered dose, he suffered an anaphylactic shock with Kounis syndrome. The patient declined any in vivo studies, so we thought of BAT as a possibility for the diagnosis. The results were remarkable, showing a very high positivity to castor oil. CONCLUSIONS: This is the second case in the world of anaphylaxis to a preparation of Testosterone, and the first one with the castor oil (also called Cremophor or Kolliphor) as responsible. El BAT was essential for the diagnosis and ulterior treatment of this patient. This is the first time, that this study with BAT, has been done with a Testosterone preparation.
Introducción: En muchos casos de alergia a medicamentos, es necesario realizar pruebas in vitro por diversos motivos. La PAB (prueba de activación de basófilos) es un arma útil en estos casos. Reporte de caso: Se trata de un hombre de 37 años en tratamiento con undecanoato de testosterona relacionado a síndrome de Klinefelter; que al momento de la última minsitración de la dosis, el paciente sufrió un choque anafiláctico acompañado de síndrome de Kounis. Por la necesidad de seguir con el tratamiento con testosterona, decidimos recurrir a la PAB para el diagnóstico, y los resultados fueron concluyentes, se documentó positividad al aceite de ricino. Conclusiones: A nivel mundial, este es el segundo caso de anafilaxia asociado a undecanoato de testosterona y el primero donde el aceite de ricino ha sido el responsable. La PAB se hizo necesaria para el diagnóstico y el posterior tratamiento de este paciente.
Assuntos
Anafilaxia , Hipersensibilidade a Drogas , Adulto , Anafilaxia/induzido quimicamente , Anafilaxia/diagnóstico , Anafilaxia/tratamento farmacológico , Basófilos , Humanos , Masculino , Testosterona/efeitos adversosRESUMO
The first formal description of the microbicidal activity of extracellular traps (ETs) containing DNA occurred in neutrophils in 2004. Since then, ETs have been identified in different populations of cells involved in both innate and adaptive immune responses. Much of the knowledge has been obtained from in vitro or ex vivo studies; however, in vivo evaluations in experimental models and human biological materials have corroborated some of the results obtained. Two types of ETs have been described-suicidal and vital ETs, with or without the death of the producer cell. The studies showed that the same cell type may have more than one ETs formation mechanism and that different cells may have similar ETs formation mechanisms. ETs can act by controlling or promoting the mechanisms involved in the development and evolution of various infectious and non-infectious diseases, such as autoimmune, cardiovascular, thrombotic, and neoplastic diseases, among others. This review discusses the presence of ETs in neutrophils, macrophages, mast cells, eosinophils, basophils, plasmacytoid dendritic cells, and recent evidence of the presence of ETs in B lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes. Moreover, due to recently collected information, the effect of ETs on COVID-19 is also discussed.
Assuntos
Armadilhas Extracelulares/imunologia , Animais , Basófilos/imunologia , COVID-19 , Eosinófilos/imunologia , Humanos , Linfócitos/imunologia , Macrófagos/imunologia , Mastócitos/imunologia , Neutrófilos/imunologiaRESUMO
Ecophysiology and conservation studies often require the prior establishment of baseline physiologic metrics. For instance, expected reference intervals for health metrics are valuable tools for veterinarians and conservationists who monitor the health status of endangered populations and species. This study establishes reference intervals for hematologic metrics in free-ranging Olrog's gull (Larus atlanticus) during the nonbreeding season. Fifty-six gulls (immature and adults) were captured and studied in Mar del Plata and neighboring coastal areas (Buenos Aires, Argentina) during the winter of 2018 (n = 22) and 2019 (n = 34). Hematocrit, red blood cells (erythrocytes), hemoglobin, mean cell volume, mean cell hemoglobin (MCH), MCH concentration, white blood cells (WBC; leukocytes), heterophils, lymphocytes, eosinophils, monocytes, and basophils were analyzed. Additionally, the variability of hematologic metrics according to body weight, sex, age, and calendar year was examined. Hematologic metrics were in line with those reported in other seabird species. Males had greater body weight and MCH than females. The heterophil to lymphocyte ratio and lymphocyte levels were higher in adults than in immatures. Hematocrit, WBC, heterophils, and basophils also varied significantly between calendar years. The results highlight the importance of appropriate metrics and reference intervals for monitoring the health status of this threatened species, and it is recommended to implement such comparative assessments among populations.
Assuntos
Charadriiformes/sangue , Estações do Ano , Envelhecimento , Animais , Argentina , Ascomicetos , Basófilos , Eosinófilos , Contagem de Eritrócitos , Índices de Eritrócitos , Feminino , Hematócrito , Hemoglobinas , Contagem de Leucócitos , Linfócitos , Masculino , MonócitosRESUMO
PURPOSE OF REVIEW: The aim of this study is to critically review the relevant literature published on basophil activation test, presenting the current knowledge and future perspectives. RECENT FINDINGS: Basophil activation test (BAT) results varied accordingly to the class of the drug studied, and have promising results in immediate hypersensitivity reactions to pyrazolone (selective reactors), neuromuscular blockers, beta-lactams, and platinum compounds, all examples of classical IgE-mediated hypersensitivity drug reactions. Currently, BAT is applied in research settings, but based in the results of our review, the test can be considered as a diagnostic tool for daily practice for selected patients and selected drugs, when the test is available, particularly for patients who experienced severe reactions and when diagnosis cannot be stablished by serum-specific IgE and skin testing, in order to avoid unnecessary drug provocations tests.
Assuntos
Teste de Degranulação de Basófilos , Basófilos/imunologia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade Imediata/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Humanos , Hipersensibilidade Imediata/diagnóstico , Fármacos Neuromusculares/efeitos adversos , Pirazolonas/efeitos adversos , beta-Lactamas/efeitos adversosRESUMO
The aim of this study was to investigate the daily rhythms of hematological, biochemical and enzymatic parameters of the blood of a nocturnal model of fish (Lophiosilurus alexandri) bred in the laboratory (F1). Thirty-six juveniles were stocked in six tanks of a recirculation aquaculture system for 20 days. The fish were exposed to a light:dark cycle of 12:12 h and were fed 1% of biomass twice a day with commercial diet. The daily rhythms of hematological, biochemical and enzymatic parameters were then measured at six sampling times "zeitgeber time = ZT" at four-hour intervals under light:dark 12:12 h (lights on = ZT0, at 8.00 a.m). No differences were observed to alkaline phosphatase, glucose, cortisol, aspartate aminotransferase, superoxide dismutase, total protein and hematocrit (p > 0.05). However, white blood cell count, Lymphocytes (LYN), Neutrophils (NEU), Eosinophil and Neutrophils to Lymphocytes ratio were significant different between sample times (p < 0.05). Also, a significant difference in alanine transaminase was observed, with a peak of production at nighttime. In contrast, glutathione peroxidase peaked at 8:00. Uric acid, magnesium and Calcium (Ca++) showed statistically significant differences (p < 0.05). A significant difference was observed (p < 0.05), with a peak of albumin at 08:00 and triglycerides at 12:00, while cholesterol was low (p < 0.05) at 08:00 and higher from 12:00 to 04:00. Cosinor analysis revealed also rhythmicity to SOD, UA, Mg and Ca++, ALB and CHO (p < 0.05). In conclusion, the time of day must be considered a key factor when using blood parameters as biomarkers for disease, health and welfare in the L. alexandri aquaculture.
Assuntos
Antioxidantes/metabolismo , Peixes-Gato/fisiologia , Ritmo Circadiano , Enzimas/sangue , Leucócitos/fisiologia , Fosfatase Alcalina , Animais , Basófilos , Glicemia , Cálcio/sangue , Eosinófilos , Comportamento Alimentar/fisiologia , Hidrocortisona/sangue , Contagem de Leucócitos , Contagem de Linfócitos , Magnésio/sangue , Neutrófilos , Ácido Úrico/sangueRESUMO
BACKGROUND: Cow's milk protein allergy is the main allergic problem during the first year of life, possibly owing to immune and gastrointestinal systems poor maturation. To prevent allergic reactions, the content and type of proteins in infant formulas resemble those of breast milk. We believe that reactions are due rather to the amount than to the type of protein. OBJECTIVE: To design a new formula with cow's milk that provides the infant with the main nutrients at an affordable cost and with lower risk for the development of allergies. METHODS: Three-phase project: product design, industrial production and ex vivo assay to assess for anemia and type I allergic reaction by CD63 expression in basophils. RESULTS: For every 100 calories, the content of protein was 2.0 g, carbohydrates 7.2 g and fat 0.5 g, which is higher than the indicated maximum value (4.5 g). Microbiologically, it was an innocuous food. CD63 expression was low in 57.1% of the babies and high in 42.9%. CONCLUSION: The new formula did not trigger any allergenic responses and can therefore be supplied to non-atopic infants.
Antecedentes: La alergia a las proteínas de la leche de vaca es el principal problema alérgico durante el primer año de vida, debido a la poca maduración de los sistemas inmunológico y gastrointestinal. Para evitar reacciones alérgicas, el contenido y tipo de proteínas de las fórmulas infantiles se asemejan a los de la leche materna. Conforme un principio de alergología, probablemente las reacciones se deben a la cantidad de proteínas más que al tipo. Objetivo: Diseñar una nueva fórmula con leche de vaca que aporte al lactante los principales nutrientes, a un bajo costo y con menor riesgo de padecer alergias. Métodos: Proyecto realizado en 3 fases: diseño del producto, producción industrial y ensayo ex vivo para evaluar mediante la expresión del CD63 en basófilos la presencia de anemia y reacción alérgica tipo I en lactantes. Resultados: Por cada 100 calorías, el contenido de proteínas fue de 2 g, de carbohidratos de 7.2 g y de grasa de 0.5 g, mayor al valor máximo indicado (4.5 g). Microbiológicamente, la fórmula láctea propuesta se trató de un alimento inocuo. La expresión del CD63 fue baja en 57.1 % de los lactantes y alta en 42.9 %. Conclusión: La nueva fórmula no desencadenó respuesta alergénica, por lo tanto, puede suministrarse a lactantes no atópicos.
Assuntos
Fórmulas Infantis/efeitos adversos , Hipersensibilidade a Leite/etiologia , Leite/efeitos adversos , Animais , Basófilos/química , Bovinos , Carboidratos da Dieta/análise , Gorduras na Dieta/análise , Proteínas Alimentares/análise , Citometria de Fluxo , Aditivos Alimentares , Microbiologia de Alimentos , Hematócrito , Hemoglobinas/análise , Humanos , Lactente , Leite/química , Leite/microbiologia , Valor Nutritivo , Tetraspanina 30/biossínteseRESUMO
A imunoterapia alérgeno-específica tem sido usada há mais de 100 anos como um tratamento de dessensibilização para doenças alérgicas, representando um método potencialmente curativo e específico. O presente estudo tem como objetivo revisar os mecanismos da imunoterapia alérgeno-específica, através de revisão bibliográfica com base em artigos publicados entre 1998 e 2016, disponíveis no banco de dados PubMed. Os mecanismos de ação da imunoterapia incluem modulação de linfócitos T e B, produção de IgG4 alérgeno-específica e redução de IgE alérgenoespecífica, migração de eosinófilos, basófilos e mastócitos nos tecidos, bem como a liberação de seus mediadores. As células T reguladoras (Treg) suprimem as células dendríticas responsáveis pela geração de células T efetoras, inibindo TH1, TH2 e TH17. As células Treg foram identificadas como peças-chave no processo de indução de tolerância periférica aos alérgenos.
Allergen-specific immunotherapy has been used for more than 100 years as a desensitizing therapy for allergic diseases, representing a potentially curative and specific method. The aim of the present study was to review the mechanisms of allergenspecific immunotherapy based on papers published between 1998 and 2016 and available in the PubMed database. The mechanisms of action of immunotherapy include modulation of T-and B-cell responses, induction of allergen-specific IgG4 and suppression of allergen-specific IgE production, migration of eosinophils, basophils, and mast cells to tissues, as well as release of their mediators. Regulatory T cells (Treg) suppress dendritic cells that support the generation of effector T cells, inhibiting TH1, TH2, and TH17 cells. Treg cells have been identified as key regulators of the induction process of peripheral allergen tolerance.