Liberación masiva de la enzima diamina oxidasa que degrada la histamina durante la anafilaxia grave en pacientes con mastocitosis
Thomas Boehm, 1 Birgit Reiter, 2 Robin Ristl, 3 Karin Petroczi, 1 Wolfgang Sperr, 4 Thomas Stimpfl, 2 Peter Valent, 4 and Bernd Jilma 1
Allergy. 2019 Mar; 74(3): 583–593.
Published online 2019 Jan 1. doi: 10.1111/all.13663 PMCID: PMC6590243 PMID: 30418682
Resumen
Antecedentes
La actividad histaminolítica mediada por la diamina oxidasa (DAO) está presente en el plasma después de la inducción de anafilaxia severa en ratas, cobayas y conejos. La heparina liberada durante la desgranulación de mastocitos en el tracto gastrointestinal podría liberar DAO de los sitios de almacenamiento sensibles a la heparina. La liberación de DAO durante la anafilaxia no se ha demostrado en humanos.
Métodos
Las concentraciones plasmáticas de DAO, triptasa e histamina de cuatro eventos graves de anafilaxia se determinaron en múltiples puntos de tiempo en serie en dos pacientes con mastocitosis sistémica. Las tasas de degradación de histamina se midieron en muestras de anafilaxia y en suero y plasma durante el embarazo con concentraciones de DAO comparables.
Resultados
Las concentraciones medias de DAO (132 ng / ml) y triptasa (304 ng / ml) aumentaron 187 y 4.0 veces, respectivamente, por encima de los valores iniciales (DAO 0.7 ng / ml, triptasa 76 ng / ml) durante la anafilaxia severa. En condiciones sin anafilaxia, las concentraciones de DAO no se elevaron en 29 pacientes con mastocitosis en comparación con voluntarios sanos y no hubo correlación entre los niveles de DAO y triptasa en pacientes con mastocitosis. La tasa de degradación de la histamina de la DAO en plasma de pacientes con mastocitosis durante la anafilaxia se ve gravemente comprometida en comparación con la DAO de muestras de embarazo.
Conclusión
Durante la anafilaxia grave en pacientes con mastocitosis, es probable que se libere DAO de los sitios de almacenamiento gastrointestinal sensibles a la heparina. Las concentraciones medidas pueden degradar la histamina, pero la actividad DAO se ve comprometida en comparación con las muestras de embarazo. Para mediciones precisas de histamina durante la anafilaxia, la inhibición de DAO es esencial para inhibir una mayor degradación de histamina después de la extracción de sangre. La determinación de los niveles de antígeno DAO podría ser de valor clínico para mejorar el diagnóstico de activación de mastocitos.
Serum levels of histamine and diamine oxidase in multiple sclerosis
Serum levels of histamine and diamine oxidase in multiple sclerosis
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Am J Clin Exp Immunol 2018;7(6):100-105 www.ajcei.us /ISSN:2164-7712/AJCEI0086352
Aryan Rafiee Zadeh1, Masih Falahatian1, Fereshteh Alsahebfosoul2
1School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; 2Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract:
Background:
Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system, mostly affecting young adults. Diamine oxidase is an enzyme essential for histamine production. Histamine which is produced mostly by mast cells can have effects on different aspects of immune system via its different histamine receptors (H1R, H2R, H3R and H4R). The crucial role of diamine oxidase and histamine in immune balance has been documented in different studies and experiments both on MS patients and on experimental allergic encephalomyelitis (EAE). In this regard, we aimed to measure the level of histamine and diamine oxidase in the serum of MS patients.
Methods:
A total number of 50 relapsing-remitting MS (RRMS) patients and 41 age and sex matched controls were enrolled in this study. Assessments of serum levels of histamine and diamine oxidase enzyme were performed using enzyme-linked immune sorbent assay (ELISA). Results: The serum levels of histamine and diamine oxidase in RRMS patients were lower than healthy controls (P-value = 0.00, for both).
Conclusion:
Our research team found significant low levels of histamine and diamine oxidase in RRMS patients; however the pathogenesis of this issue was unclear.
¿Se subestiman Las cantidades de aminas biógenas en las dietas bajas en histamina ?
Las dietas bajas en histamina se utilizan actualmente para reducir los síntomas de la Intolerancia a la Histamina producida por déficit de DAO, un trastorno en la homeostasis de la histamina alimentari que aumenta sus niveles en sangre, debido principalmente a la reducción de la actividad de la diamina-oxidasa (DAO).
De hecho, estas dietas bajas en histamina excluyen alimentos, muchos de ellos de origen vegetal, que los pacientes asocian con la aparición de la sintomatología de este síndrome.
Nuevos datos sobre el déficit de DAO producido por aminas biógenas
Investigadores de la Universidad de Barcelona y de la Xarxa de Referència en Tecnologia dels Aliments de la Generalitat de Catalunya (XaRTA) han publicado recientemente un artículo científico en la Revista Foods en el que aportan nuevos datos. El objetivo de este estudio fue revisar los datos existentes sobre la histamina y otras aminas biógenas en alimentos no fermentados de origen vegetal, así como sobre su origen y evolución durante el almacenamiento o el proceso culinario.
Los resultados del estudio han mostrado diferencias significativas en las que los únicos productos de origen vegetal con importantes niveles de histamina fueron berenjenas, espinacas, tomate y aguacate, cada una mostrando una gran variabilidad en el contenido.
Efecto de saturación de la Diamino Oxidasa por las aminas biógenas
Por otra parte, aminas biogenas como la putrescina se ha encontrado en prácticamente todos los alimentos de origen vegetal, probablemente debido a su origen fisiológico. El alto contenido de la putrescina en ciertos productos también podría estar relacionado con la activación de la sintomatología del déficit de DAO. Este efecto puede ser debido por competición enzimática de la putrescina con la histamina, secuestrando de este modo la putrescina a la Diamino Oxidasa, evitando así que se metabolice la histamina y propiciando que sea absorbida en el intestino y propagada por todo el organismo.
Además, los altos contenidos de la molécula espermina, presentes en algunos alimentos, también deben ser tenidos en cuenta en estas dietas, ya que también puede ser metabolizada por DAO, aunque con menor afinidad, y por tanto también pueden secuestrar a la DAO impidiendo que ésta metabolice a la histamina.
De este modo, como conclusión se recomienda consumir alimentos de origen vegetal hervidos o si son de la máxima frescura. De este forma se pretende reducir la ingesta de aminas biógenas y sus efectos sintomatológicos por competición enzimática con la histamina de la DAO .
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Biogenic Amines in Plant-Origin Foods: Are they Frequently Underestimated in Low-Histamine Diets?
Biogenic Amines in Plant-Origin Foods: Are they Frequently Underestimated in Low-Histamine Diets?
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Foods 2018, 7(12), 205.
Autors information:
Abstract
Low-histamine diets are currently used to reduce symptoms of histamine intolerance, a disorder in histamine homeostasis that increases plasma levels, mainly due to reduced diamine-oxidase (DAO) activity. These diets exclude foods, many of them of plant origin, which patients associate with the onset of the symptomatology. This study aimed to review the existing data on histamine and other biogenic amine contents in nonfermented plant-origin foods, as well as on their origin and evolution during the storage or culinary process. The only plant-origin products with significant levels of histamine were eggplant, spinach, tomato, and avocado, each showing a great variability in content. Putrescine has been found in practically all plant-origin foods, probably due to its physiological origin. The high contents of putrescine in certain products could also be related to the triggering of the symptomatology by enzymatic competition with histamine. Additionally, high spermidine contents found in some foods should also be taken into account in these diets, because it can also be metabolized by DAO, albeit with a lower affinity. It is recommended to consume plant-origin foods that are boiled or are of maximum freshness to reduce biogenic amine intake.
Cite this article:
Sánchez-Pérez, S.; Comas-Basté, O.; Rabell-González, J.; Veciana-Nogués, M.T.; Latorre-Moratalla, M.L.; Vidal-Carou, M.C. Biogenic Amines in Plant-Origin Foods: Are they Frequently Underestimated in Low-Histamine Diets? Foods 2018, 7, 205.
DOI: https://doi.org/10.3390/foods7120205
Microbial patterns in patients with histamine intolerance
Microbial patterns in patients with histamine intolerance.
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J Physiol Pharmacol. 2018 Aug;69(4). doi: 10.26402/jpp.2018.4.09. Epub 2018 Dec 9.
Author information
- 1
- First Department of Medicine, Hector Center for Nutrition, Exercise and Sports, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Erlangen, Germany.
- 2
- Second Department of Medicine, Thuringia-Clinic Saalfeld, Saalfeld/Saale, Germany.
- 3
- First Department of Medicine, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Erlangen, Germany.
- 4
- First Department of Medicine, Hector Center for Nutrition, Exercise and Sports, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Erlangen, Germany. yurdaguel.zopf@uk-erlangen.de.
Abstract
Histamine intolerance represents a controversially discussed disorder. Besides an impaired degradation of orally supplied histamine due to diamine oxidase (DAO) deficiency, a deranged gut flora may also contribute to elevated histamine levels. Our aim was to determine the intestinal bacterial composition in patients with proven histamine intolerance in comparison to other food intolerances and healthy controls. A total of 64 participants were included in the study, encompassing 8 patients with histamine intolerance (HIT), 25 with food hypersensitivity (FH), 21 with food allergy and 10 healthy controls (HC). All participants underwent blood testing for total and food-specific immunoglobulin E, plasma histamine and DAO serum activity. Stool samples were used to analyze stool histamine and zonulin levels and bacterial composition by 16s rRNA sequencing. No significant differences in stool histamine levels were observed, but HIT patients showed elevated levels of stool zonulin. Microbiota analysis revealed increased levels of Proteobacteria (5.4%) and a significantly reduced alpha-diversity in the HIT group (P = 0.019). On family level, HC showed a significantly higher abundance of Bifidobacteriaceae compared to other study groups (P = 0.005), with lowest levels in the HIT group (P = 0.036). Also significantly reduced abundances of the genera Butyricimonas (P = 0.026) and Hespellia (P = 0.025) were observed in the HIT patients, whereas Roseburia were significantly elevated (P = 0.021). We concluded that the altered occurrence of Proteobacteria and Bifidobacteriaceae, reduced alpha-diversity as well as elevated stool zonulin levels suggest a dysbiosis and intestinal barrier dysfunction in histamine intolerant patients, which in turn may play an important role in driving disease pathogenesis.
- PMID:
- 30552302
- DOI:
- 10.26402/jpp.2018.4.09
Conformational Design and Characterisation of a Truncated Diamine Oxidase from Arthrobacter globiformis
Conformational Design and Characterisation of a Truncated Diamine Oxidase from Arthrobacter globiformis
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Abstract
A functional mini protein can be developed by miniaturising its size. The minimisation technique provides an excellent model system for studying native enzymes, especially in creating an alternative novel biocatalyst. Miniaturised proteins may have enhanced stability, a crucial characteristic for large-scale production and industrial applications. In this study, a huge enzyme molecule, known as diamine oxidase (DAO, comprising 700 amino acids), was selected to undergo the process.
Methods
Results
Intolerancia a la histamina: Causas y Soluciones – Dr. David Jockers
Emitido en directo el 10 ago. 2018 – Dr David Jockers – Idioma: Inglés.
La intolerancia a la histamina, sus causas y soluciones están directamente relacionadas con el déficit de DAO y con la reducción de la actividad de la enzima diamino oxidasa.
En este vídeo el Dr. David Jockers habla acerca de la molécula histamina, y profundiza en cuáles son sus efectos fisiológicos y patológicos en el organismo y cuáles son los síntomas de la intolerancia a la histamina. Por otra parte nos muestra cuáles son los alimentos con altos niveles de histamina y en qué consiste el déficit de DAO, el cual es la causa principal de la intolerancia a la histamina, y nos habla acerca de sus orígenes: genético, farmacológico y patológico.
Por último también aborda el tema de los tratamientos para el déficit de DAO y la intolerancia a la histamina.
Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance
Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance.
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Eur J Clin Nutr. 2018 Jul 18. doi: 10.1038/s41430-018-0260-5. [Epub ahead of print]
Author information
- 1
- Immunology and Pathophysiology, Otto Loewi Research Center, Medical University of Graz, Heinrichstrasse 31a, A-8010, Graz, Austria.
- 2
- Institute of Laboratory Medicine, General Hospital Steyr, Sierninger Straße 170, A-4400, Steyr, Austria.
- 3
- Clinical Institute of Medical and Chemical Laboratory Diagnosis, Medical University of Graz, Auenbruggerplatz 30, A-8036, Graz, Austria.
- 4
- Practice for General Internal Medicine, Dr. Theodor Körnerstrasse 19b, A-8600, Bruck, Austria. w.schnedl@dr-schnedl.at.
Abstract
Diagnosis of histamine intolerance (HIT) has been based on low serum diamine oxidase (DAO) values, functional gastrointestinal disorders and improvement of symptoms with a histamine-reduced diet (HRD). In a retrospective analysis of outpatients’ charts we identified 101 patients with HIT. After a median of 13 months, a questionnaire was distributed to the patients so that they could be classified into four diet-compliance groups. Calculated with all 101 patients we found an increase of serum DAO values due to a HRD. In the 63 patients that completed the questionnaire, we found that 50 patients had improvement of symptoms or no continuing symptoms. A significant increase of serum DAO levels was found in the patients with strict and occasional diet compliance. Therefore, we demonstrate that a HRD is not only improving symptoms in HIT, but is causing an increase in serum DAO values that correlates with the degree of diet compliance.
- PMID:
- 30022117
- DOI:
- 10.1038/s41430-018-0260-5
Low-histamine diet supplemented with exogenous diamine oxidase enzyme is useful for treating migraine in patients with DAO Deficiency
Low-histamine diet supplemented with exogenous diamine oxidase enzyme is useful for treating migraine in patients with DAO Deficiency.
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Ann Nutr Metab 2018;73 (suppl 2); 1-93
A.Duelo; M.Berbel; H.Mantecon-Laviguerie; O.Comas-Basté; M.L.Latorre-Moratalla; M.T.Veciana-Noguès; M.C.Vidal-Carou.
Departament of Nutrition, Instituto Clónico del Déficit de DAO (ICDDAO), Sant Cugat del Vallés. Spain; Departament de Nutrició, Ciències de l’Alimentació i Gastonomia. Facultat de Farmàcia i Ciències de l’Alimentació.INSA-UB.XaRTA.Universitat de Barcelona.Santa Coloma de Gramanet. Spain
Spanish Nutrition Society SEÑ and the Catalan Association of Food Science (ACCA), Barcelona, Spain, june 27-29, 2018
Introduction:
Low-histamine diets and/or exogenous diamine oxidase (DAO) supplementation are currently used to treat symptoms of histamine intolerance (IH), a disorder in histamine homeostasis that increases its plasma levels, mainly dou to DAO deficiency. Headache is the most recognized symptoms.
Objectives:
To assess the effectiveness of a low-histamine diet plus a DAO enzyme supplement on the remision of migraine in subjects with DAO deficiency.
Methods:
An intervention study was carried out in 212 individuals with a migraine diagnosis by a neurologist according to the International Classification of Headache Disorders and wih DAO deficiency (DAO <80 HDU/ml). Subjects followed a 3-month low-histamine diet based on the exclusion of foods considered rich in histamine or other biogenic amines and usually related to the onset of HI symptoms, such as fermented products (cheese, dry-fermented sausage, wine, beer), semi-preserved and canned fish, shellfish, certain fruits and vegetables (spinach, tomato, egg-plant, avocado, citrus, bananas, strawberries, pineapple, nuts) and chocolate. A DAO supplement was administrered before break-fast, lunch and dinner. Outcomes assessed were duration and number of attacks and perception of pain intensity with a score-scale fom 0 (absence) to 10.
Results:
Most subjects showed and improvement in migraines after the 3-month treatment: 34.9% reported complete remission and another 35.8% had a reduced number of migraines episodes per month of less duration and pain intensity. The treatment was less successful in 29.3% of patients. On average, when comparing baseline and final values after treatment, all outcomes were significantly reduced: 8 to 2 attacks per month, 24 to 3 hours of pain and 8 to 4 in pain intensity scoring.
Conclusions:
A low-histamine diet supplemented with the DAO enzyme for three months was useful in reducing the number of attacks, duration and intensity of pain in migraineous patients with DAO deficiency.
DOI: 10.11.59/000490752
What about legumes as a plant source of the DAO enzime?
What about legumes as a plant source of the DAO enzime?
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Ann Nutr Metab 2018;73 (suppl 2): 1-93
Spanish Nutrition Society SEÑ and the Catalan Association of Food Science (ACCA), Barcelona, Spain, june 27-29, 2018
O.Comas-Basté; S.Sánchez-Pérez; R.I. Garza-Guajardo; M.L.Latorre-Moratalla ; M.T.Veciana-Nogués; M.C.Vidal-Carou.
Departament de Nutrició, Ciències de l’Alimentació i Gastonomia. Facultat de Farmàcia i Ciències de l’Alimentació.INSA-UB.XaRTA.Universitat de Barcelona.Santa Coloma de Gramanet.Spain
Introduction:
The use of exogenous diamine oxidase (DAO) enzyme has been recently postulated as a potential strategy for the treatment of histamine intolerance, a disorder in the homeostasis of histamine caused by a reduction of its intestinal degradation. Dietary supplements based on gastro-resistant encapsulated porcine kidney protein extract ara available on the market to reduce the symptoms of this intolerance. Although with scarce scientific research, there are some references about the potential of pea seedlings as a source of DAO.
Objectives:
To study the capacity of legumes and their sprouts to reduce histamine in vitro and evaluate the influence of different growing conditions on this enzymatic activity. If confirmed, legumes could become and advantageous alternative to porcine DAO enzyme from a productive and sustainable perspective.
Methods:
In vitro DAO activity was measured through and enzymatic assay and the subsequent analysis of remaining histamine by UHPLC-FL. Analysed samples were both raw pulses and prouts of lentils, beans (white, red and black), broad beans, peas, chickpeas and soy.
DOI: 10.11.59/000490752