Summary of Study ST001655

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001061. The data can be accessed directly via it's Project DOI: 10.21228/M8JQ37 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study ID	ST001655
Study Title	Characterization of anaphylaxis reveals different metabolic changes depending on severity and triggers - NMR (part-I)
Study Summary	Background: Despite its increasing incidence, the underlying molecular processes of anaphylaxis remain unclear and there are not known biomarkers for appropriate diagnosis. The mechanism associated to the reactions still needs to be clarified in humans. The rapid onset and potentially fatal outcome in the absence of managed treatment, prevent its study and prompt obvious technical and ethical implications. Methods: Twenty episodes of anaphylaxis were analyzed. Sera was collected at different times: during the acute phase (T1), the recovery phase (T2) and around 2-3 months after the anaphylactic reaction (T0). The analysis included untargeted metabolomics combining liquid chromatography coupled to mass spectrometry (LC-MS) and proton-nuclear magnetic resonance (1H-NMR). Reactions were classified according to the trigger (food and/or drug) and severity (moderate and severe). Results: “Food T1 vs T2” and “moderate T1 vs T2” anaphylaxis comparisons showed clear metabolic patterns during the onset of an anaphylactic reaction, which differed from those induced by drugs, food+drug or severe anaphylaxis “T1 vs T2”. Moreover, the model of food anaphylaxis was able to distinguish the well-characterized IgE (beta-lactam) from non-IgE- mediated anaphylaxis (NSAIDs), suggesting a differential metabolic pathway associated with the mechanism of action. Moreover, metabolic differences between “moderate vs severe” at T1 and T0 were studied. Among the metabolites, glucose, lipids, cortisol, betaine and oleamide were observed altered. Conclusions: The results of the study provide the first evidence that different anaphylactic triggers, induce differential metabolic changes. Besides, the basal status might identify high risk patients, thus opening new ways to understand, diagnose and treat anaphylaxis.
Institute	The Centre of Metabolomics and Bioanalysis
Department	Analytical chemistry
Last Name	Obeso Montero
First Name	David
Address	Av. de Montepríncipe, s/n
Email	david.obesomontero@beca.ceu.es
Phone	607535650
Submit Date	2021-01-18
Num Groups	2 groups
Total Subjects	20
Raw Data Available	Yes
Raw Data File Type(s)	d
Analysis Type Detail	NMR
Release Date	2022-01-18
Release Version	1

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Project:

Project ID:	PR001061
Project DOI:	doi: 10.21228/M8JQ37
Project Title:	Characterization of anaphylaxis reveals different metabolic changes depending on severity and triggers.
Project Summary:	Despite its increasing incidence, the underlying molecular processes of anaphylaxis remain unclear and there are not known biomarkers for appropriate diagnosis. The mechanism associated to the reactions still needs to be clarified in humans. The rapid onset and potentially fatal outcome in the absence of managed treatment, prevent its study and prompt obvious technical and ethical implications. Twenty episodes of anaphylaxis were analyzed. Sera was collected at different times: during the acute phase (T1), the recovery phase (T2) and around 2-3 months after the anaphylactic reaction (T0). The analysis included untargeted metabolomics combining liquid chromatography coupled to mass spectrometry (LC-MS) and proton-nuclear magnetic resonance (1H-NMR). Reactions were classified according to the trigger (food and/or drug) and severity (moderate and severe). “Food T1 vs T2” and “moderate T1 vs T2” anaphylaxis comparisons showed clear metabolic patterns during the onset of an anaphylactic reaction, which differed from those induced by drugs, food+drug or severe anaphylaxis “T1 vs T2”. Moreover, the model of food anaphylaxis was able to distinguish the well-characterized IgE (beta-lactam) from non-IgE- mediated anaphylaxis (NSAIDs), suggesting a differential metabolic pathway associated with the mechanism of action. Moreover, metabolic differences between “moderate vs severe” at T1 and T0 were studied. Among the metabolites, glucose, lipids, cortisol, betaine and oleamide were observed altered. The results of the study provide the first evidence that different anaphylactic triggers, induce differential metabolic changes. Besides, the basal status might identify high risk patients, thus opening new ways to understand, diagnose and treat anaphylaxis.
Institute:	Hospital Universitari i Politècnic La Fe
Department:	Subdirección Médica, Departament de Salut València La Fe.
Last Name:	Hernández Fernández de Rojas
First Name:	Dolores
Address:	Avinguda de Fernando Abril Martorell, 106, 46026 València, Valencia, España.
Email:	hernandez_dol@gva.es
Phone:	91 372 47 00 ext. 4662

Subject:

Subject ID:	SU001732
Subject Type:	Human
Subject Species:	Homo sapiens
Taxonomy ID:	9606
Gender:	Male and female

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id	local_sample_id	Trigger	Severity	Time
SA151815	P15_t0	Drug	Mild	Time 0
SA151816	P15_t1	Drug	Mild	Time 1
SA151817	P17_t0	Drug	Moderate	Time 0
SA151818	P1_t0	Drug	Moderate	Time 0
SA151819	P3_t0	Drug	Moderate	Time 0
SA151820	P1_t1	Drug	Moderate	Time 1
SA151821	P17_t1	Drug	Moderate	Time 1
SA151822	P3_t1	Drug	Moderate	Time 1
SA151823	P1_t2	Drug	Moderate	Time 2
SA151824	P17_t2	Drug	Moderate	Time 2
SA151825	P19_t0	Drug	Severe	Time 0
SA151826	P14_t0	Drug	Severe	Time 0
SA151827	P4_t0	Drug	Severe	Time 0
SA151828	P7_t0	Drug	Severe	Time 0
SA151829	P13_t0	Drug	Severe	Time 0
SA151830	P4_t1	Drug	Severe	Time 1
SA151831	P13_t1	Drug	Severe	Time 1
SA151832	P14_t1	Drug	Severe	Time 1
SA151833	P19_t1	Drug	Severe	Time 1
SA151834	P7_t1	Drug	Severe	Time 1
SA151835	P7_t2	Drug	Severe	Time 2
SA151836	P13_t2	Drug	Severe	Time 2
SA151837	P14_t2	Drug	Severe	Time 2
SA151838	P19_t2	Drug	Severe	Time 2
SA151839	P4_t2	Drug	Severe	Time 2
SA151840	P2_t0	Food	Moderate	Time 0
SA151841	P16_t0	Food	Moderate	Time 0
SA151842	P9_t0	Food	Moderate	Time 0
SA151843	P18_t0	Food	Moderate	Time 0
SA151844	P2_t1	Food	Moderate	Time 1
SA151845	P9_t1	Food	Moderate	Time 1
SA151846	P10_t1	Food	Moderate	Time 1
SA151847	P18_t1	Food	Moderate	Time 1
SA151848	P16_t1	Food	Moderate	Time 1
SA151849	P9_t2	Food	Moderate	Time 2
SA151850	P18_t2	Food	Moderate	Time 2
SA151851	P2_t2	Food	Moderate	Time 2
SA151852	P16_t2	Food	Moderate	Time 2
SA151853	P10_t2	Food	Moderate	Time 2
SA151854	P11_t0	Food	Severe	Time 0
SA151855	P11_t1	Food	Severe	Time 1
SA151856	P11_t2	Food	Severe	Time 2
SA151857	P5_t1	Idiopatic	Moderate	Time 1
SA151858	P5_t2	Idiopatic	Moderate	Time 2
SA151859	P12_t0	Idiopatic	Severe	Time 0
SA151860	P6_t0	Idiopatic	Severe	Time 0
SA151861	P6_t1	Idiopatic	Severe	Time 1
SA151862	P12_t1	Idiopatic	Severe	Time 1
SA151863	P12_t2	Idiopatic	Severe	Time 2
SA151864	P6_t2	Idiopatic	Severe	Time 2
SA151865	P20_t0	Other	Moderate	Time 0
SA151866	P8_t0	Other	Moderate	Time 0
SA151867	P20_t1	Other	Moderate	Time 1
SA151868	P8_t1	Other	Moderate	Time 1
SA151869	P8_t2	Other	Moderate	Time 2

Showing results 1 to 55 of 55

Showing results 1 to 55 of 55

Collection:

Collection ID:	CO001725
Collection Summary:	A prospective clinical and observational study of patients with anaphylactic reactions was performed. Patients of all ages and both sexes were recruited at outpatient clinics and the departments of Emergency, and other services at Hospital La Fe. All fulfilled clinical criteria of anaphylaxis and severity was graded following the classification by Brown, et al3. Patients were classified as food, drug or idiopathic origin, as well as in mild, moderate or severe according to the number of organs affected and clinical symptoms. The allergy evaluation was conducted by the Allergology Service of Hospital La Fe. The ethical committee approved the study protocol and all subjects were informed and provided written consent. Serum samples were taken during the acute moment of the reaction at the first moment of medical attention (< 2h, hereafter referred as ‘T1’), and after clinical recovery (approximately 2-4h later, referred to as ‘T2’). Patients were treated according to the Galaxy 2016 practical guide, using all necessary drugs to rescue them. Samples were collected, following specific standard operating procedures (SOPs)31-33. Briefly, these were collected in a vacutainer tube (Ref. 368965) and processed within the first 30 to 60 min after blood extraction. Sample aliquots were stored at -80ºC until further analyses. Subsequently, between 2-3 months after the anaphylaxis, a serum sample was taken when the allergy evaluation was performed (basal state, called ‘T0’).
Sample Type:	Blood (serum)
Storage Conditions:	-80℃

Treatment:

Treatment ID:	TR001745
Treatment Summary:	Patients were treated according to the Galaxy 2016 practical guide, using all necessary drugs to rescue them.

Sample Preparation:

Sampleprep ID:	SP001738
Sampleprep Summary:	After thawing the samples, 150 µL of cold acetonitrile (0.1% formic acid, v/v) was added to 50 µL of serum, vortex and kept at -20ºC for 30 min for protein precipitation. Then, 25 µl of cleaned supernatant were transferred to a 96 well-plate for UPLC-MS analysis. Finally, 125 µL of H2O (0.1% formic acid, v/v), and 2 µL of internal standard (IS) mix solution, containing reserpine, leucine enkephaline, caffeine-d9 and phenylalanine-d5 in H20:CH3OH (1:1, 0.1% v/v formic acid) at 20 µM were added to each sample. Blank samples were prepared by replacing serum by ultrapure H20 in order to identify potential artefacts from the tube, reagents and other materials. A quality control (QC) was prepared by mixing 10 µL from each prepared sample. Samples were randomly injected in the chromatographic system (UPLC-ToF-MS) injection a QC every 6 serum samples in order to avoid intra-batch variability, as well as to enhance quality and reproducibility. Blank analysis was performed at the beginning and at end of the sequence. Sample stability and analytical drift were investigated through the internal standard intensities.

Sampleprep ID:

SP001738

Sampleprep Summary:

After thawing the samples, 150 µL of cold acetonitrile (0.1% formic acid, v/v) was added to 50 µL of serum, vortex and kept at -20ºC for 30 min for protein precipitation. Then, 25 µl of cleaned supernatant were transferred to a 96 well-plate for UPLC-MS analysis. Finally, 125 µL of H2O (0.1% formic acid, v/v), and 2 µL of internal standard (IS) mix solution, containing reserpine, leucine enkephaline, caffeine-d9 and phenylalanine-d5 in H20:CH3OH (1:1, 0.1% v/v formic acid) at 20 µM were added to each sample. Blank samples were prepared by replacing serum by ultrapure H20 in order to identify potential artefacts from the tube, reagents and other materials. A quality control (QC) was prepared by mixing 10 µL from each prepared sample. Samples were randomly injected in the chromatographic system (UPLC-ToF-MS) injection a QC every 6 serum samples in order to avoid intra-batch variability, as well as to enhance quality and reproducibility. Blank analysis was performed at the beginning and at end of the sequence. Sample stability and analytical drift were investigated through the internal standard intensities.

Analysis:

Analysis ID:	AN002702
Analysis Type:	NMR

NMR:

NMR ID:	NM000202
Analysis ID:	AN002702
Instrument Name:	Bruker 500MHz spectrometer
Instrument Type:	FT-NMR
NMR Experiment Type:	1D-1H
Spectrometer Frequency:	500MHz