Summary of Study ST002948
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 PR001833. The data can be accessed directly via it's Project DOI: 10.21228/M8SB0G 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.
Study ID | ST002948 |
Study Title | Multi-omics Approach Reveals a Specific Profile in Severe Asthmatic Patients Treated with Mepolizumab or Omalizumab |
Study Summary | The prevalence and severity of asthma continue to increase, and patients with uncontrolled severe asthma may require additional biological treatment. Given the pathophysiological heterogeneity underlying severe asthma, there is a lack of reliable biomarkers to monitor treatment response. In this context, this study aimed to identify potential biomarkers for monitoring the response to either Mepolizumab or Omalizumab in severe asthmatic patients using metabolomics and proteomics. Severe asthmatic patients who were prescribed either Mepolizumab (n=36) or Omalizumab (n=20) were followed during treatment, and serum samples were collected before treatment (T0), and both at 6 (T1) and 18 months (T2) after starting biological treatment. Treatment monitoring was performed by the analysis of a set of inflammatory metabolites and proteins using targeted metabolomic and proteomic approaches, along with the study of clinical variables such as the number of blood eosinophils, hospitalizations, and severe exacerbations. Mepolizumab and Omalizumab induced changes in the metabolomic and proteomic profiles of severe asthmatic patients. For both treatments, the greatest differences in metabolites were seen at T1 and maintained up to T2, whereas protein changes were seen throughout the treatment. Notable changes associated with anti-inflammatory effects included a decrease in several fatty acids, sphingosine-1-phosphate (S1P), L-arginine, and IL-10RA. Interestingly, S1P was the main feature that correlated significantly with eosinophilia in both treatments. These results unveil underlying molecular mechanisms that occur during Mepolizumab and Omalizumab treatments and provide potential biomarkers for monitoring treatment response in severe asthmatic patients. |
Institute | CEMBIO |
Last Name | Contreras |
First Name | Nuria |
Address | Urb. Montepríncipe s/n, Ctra. Boadilla del Monte km 5.3, Madrid 28668, Spain |
nuria.contrerasgomez1@ceu.es | |
Phone | +3491372470014750 |
Submit Date | 2023-10-27 |
Num Groups | 2 |
Total Subjects | 54 |
Raw Data Available | Yes |
Raw Data File Type(s) | mzML |
Analysis Type Detail | LC-MS |
Release Date | 2025-01-20 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
Project ID: | PR001833 |
Project DOI: | doi: 10.21228/M8SB0G |
Project Title: | Targeted metabolomics in severe asthmatic patients treated with biologics. |
Project Type: | Targeted MS analysis |
Project Summary: | Severe asthmatic patients prescribed either Mepolizumab or Omalizumab were followed during treatment, and serum samples were collected before treatment (T0), and both at 6 (T1) and 18 months (T2) after starting biological treatment. Treatment monitoring was performed by the analysis of a set of inflammatory metabolites using targeted metabolomics. |
Institute: | CEMBIO |
Last Name: | Contreras |
First Name: | Nuria |
Address: | Urb. Montepríncipe s/n, Ctra. Boadilla del Monte km 5.3, Madrid 28668, Spain |
Email: | nuria.contrerasgomez1@ceu.es |
Phone: | +3491372470014750 |
Subject:
Subject ID: | SU003061 |
Subject Type: | Human |
Subject Species: | Homo sapiens |
Taxonomy ID: | 9606 |
Age Or Age Range: | ≥ 18 years |
Gender: | Male and female |
Human Medications: | Mepolizumab or Omalizumab |
Species Group: | Mammals |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
mb_sample_id | local_sample_id | Time | Treatment |
---|---|---|---|
SA320904 | Me-T0-19 | T0 | Mepolizumab |
SA320905 | Me-T0-18 | T0 | Mepolizumab |
SA320906 | Me-T0-17 | T0 | Mepolizumab |
SA320907 | Me-T0-20 | T0 | Mepolizumab |
SA320908 | Me-T0-21 | T0 | Mepolizumab |
SA320909 | Me-T0-23 | T0 | Mepolizumab |
SA320910 | Me-T0-22 | T0 | Mepolizumab |
SA320911 | Me-T0-16 | T0 | Mepolizumab |
SA320912 | Me-T0-10 | T0 | Mepolizumab |
SA320913 | Me-T0-05 | T0 | Mepolizumab |
SA320914 | Me-T0-04 | T0 | Mepolizumab |
SA320915 | Me-T0-03 | T0 | Mepolizumab |
SA320916 | Me-T0-06 | T0 | Mepolizumab |
SA320917 | Me-T0-07 | T0 | Mepolizumab |
SA320918 | Me-T0-25 | T0 | Mepolizumab |
SA320919 | Me-T0-08 | T0 | Mepolizumab |
SA320920 | Me-T0-11 | T0 | Mepolizumab |
SA320921 | Me-T0-27 | T0 | Mepolizumab |
SA320922 | Me-T0-40 | T0 | Mepolizumab |
SA320923 | Me-T0-39 | T0 | Mepolizumab |
SA320924 | Me-T0-38 | T0 | Mepolizumab |
SA320925 | Me-T0-41 | T0 | Mepolizumab |
SA320926 | Me-T0-42 | T0 | Mepolizumab |
SA320927 | Me-T0-45 | T0 | Mepolizumab |
SA320928 | Me-T0-43 | T0 | Mepolizumab |
SA320929 | Me-T0-37 | T0 | Mepolizumab |
SA320930 | Me-T0-35 | T0 | Mepolizumab |
SA320931 | Me-T0-30 | T0 | Mepolizumab |
SA320932 | Me-T0-29 | T0 | Mepolizumab |
SA320933 | Me-T0-01 | T0 | Mepolizumab |
SA320934 | Me-T0-31 | T0 | Mepolizumab |
SA320935 | Me-T0-32 | T0 | Mepolizumab |
SA320936 | Me-T0-34 | T0 | Mepolizumab |
SA320937 | Me-T0-33 | T0 | Mepolizumab |
SA320938 | Me-T0-26 | T0 | Mepolizumab |
SA320939 | Me-T0-12 | T0 | Mepolizumab |
SA320940 | O-T0-04 | T0 | Omalizumab |
SA320941 | O-T0-08 | T0 | Omalizumab |
SA320942 | O-T0-23 | T0 | Omalizumab |
SA320943 | O-T0-03 | T0 | Omalizumab |
SA320944 | O-T0-12 | T0 | Omalizumab |
SA320945 | O-T0-14 | T0 | Omalizumab |
SA320946 | O-T0-13 | T0 | Omalizumab |
SA320947 | O-T0-05 | T0 | Omalizumab |
SA320948 | O-T0-06 | T0 | Omalizumab |
SA320949 | O-T0-01 | T0 | Omalizumab |
SA320950 | O-T0-22 | T0 | Omalizumab |
SA320951 | O-T0-16 | T0 | Omalizumab |
SA320952 | O-T0-18 | T0 | Omalizumab |
SA320953 | O-T0-09 | T0 | Omalizumab |
SA320954 | O-T0-17 | T0 | Omalizumab |
SA320955 | O-T0-20 | T0 | Omalizumab |
SA320956 | O-T0-02 | T0 | Omalizumab |
SA320957 | O-T0-10 | T0 | Omalizumab |
SA320958 | Me-T1-20 | T1 | Mepolizumab |
SA320959 | Me-T1-11 | T1 | Mepolizumab |
SA320960 | Me-T1-29 | T1 | Mepolizumab |
SA320961 | Me-T1-10 | T1 | Mepolizumab |
SA320962 | Me-T1-21 | T1 | Mepolizumab |
SA320963 | Me-T1-31 | T1 | Mepolizumab |
SA320964 | Me-T1-30 | T1 | Mepolizumab |
SA320965 | Me-T1-19 | T1 | Mepolizumab |
SA320966 | Me-T1-18 | T1 | Mepolizumab |
SA320967 | Me-T1-26 | T1 | Mepolizumab |
SA320968 | Me-T1-25 | T1 | Mepolizumab |
SA320969 | Me-T1-17 | T1 | Mepolizumab |
SA320970 | Me-T1-16 | T1 | Mepolizumab |
SA320971 | Me-T1-22 | T1 | Mepolizumab |
SA320972 | Me-T1-12 | T1 | Mepolizumab |
SA320973 | Me-T1-27 | T1 | Mepolizumab |
SA320974 | Me-T1-23 | T1 | Mepolizumab |
SA320975 | Me-T1-08 | T1 | Mepolizumab |
SA320976 | Me-T1-06 | T1 | Mepolizumab |
SA320977 | Me-T1-39 | T1 | Mepolizumab |
SA320978 | Me-T1-01 | T1 | Mepolizumab |
SA320979 | Me-T1-38 | T1 | Mepolizumab |
SA320980 | Me-T1-03 | T1 | Mepolizumab |
SA320981 | Me-T1-40 | T1 | Mepolizumab |
SA320982 | Me-T1-41 | T1 | Mepolizumab |
SA320983 | Me-T1-45 | T1 | Mepolizumab |
SA320984 | Me-T1-43 | T1 | Mepolizumab |
SA320985 | Me-T1-42 | T1 | Mepolizumab |
SA320986 | Me-T1-35 | T1 | Mepolizumab |
SA320987 | Me-T1-37 | T1 | Mepolizumab |
SA320988 | Me-T1-34 | T1 | Mepolizumab |
SA320989 | Me-T1-33 | T1 | Mepolizumab |
SA320990 | Me-T1-04 | T1 | Mepolizumab |
SA320991 | Me-T1-32 | T1 | Mepolizumab |
SA320992 | Me-T1-07 | T1 | Mepolizumab |
SA320993 | Me-T1-05 | T1 | Mepolizumab |
SA320994 | O-T1-01 | T1 | Omalizumab |
SA320995 | O-T1-16 | T1 | Omalizumab |
SA320996 | O-T1-02 | T1 | Omalizumab |
SA320997 | O-T1-06 | T1 | Omalizumab |
SA320998 | O-T1-05 | T1 | Omalizumab |
SA320999 | O-T1-04 | T1 | Omalizumab |
SA321000 | O-T1-03 | T1 | Omalizumab |
SA321001 | O-T1-08 | T1 | Omalizumab |
SA321002 | O-T1-09 | T1 | Omalizumab |
SA321003 | O-T1-22 | T1 | Omalizumab |
Collection:
Collection ID: | CO003054 |
Collection Summary: | Whole blood from the three hospital-scheduled visits was incubated with a clotting agent in Vacutainer SST II tubes. Samples were placed at room temperature for 30 min and then centrifuged at 2000 x g for 10 min for serum recovery. Serum samples were stored at -80ºC until further metabolomic analyses. |
Sample Type: | Blood (serum) |
Storage Conditions: | -80℃ |
Treatment:
Treatment ID: | TR003070 |
Treatment Summary: | Patients were prescribed add-on biological treatments following the GINA guidelines. Mepolizumab was used in patients with >300 eosinophils/µL (without corticosteroids treatment) or >100 eosinophils/µL (with corticosteroids). Meanwhile, Omalizumab was chosen in uncontrolled severe allergic asthmatics with serum IgE levels between 30 and 1500 IU/mL and body weight within the dosing range. |
Sample Preparation:
Sampleprep ID: | SP003067 |
Sampleprep Summary: | For sample preparation, 50 µL of serum was mixed with 150 µL of cold (−20 °C) methanol: ethanol mix (MeOH:EtOH) (1:1). Then, serum samples were vortex-mixed for 1 min, placed on ice for 15 min and centrifuged at 16000× g for 20 min at 4 °C. Subsequently, 70 µL of the supernatant was transferred into an LC vial and mixed with 50 µL of ISTD mix, (with a final concentration of 0.2 µg/mL for HILIC and 0.3 µg/mL for re-versed-phase method) and 440 µL of the initial conditions of the mobile phases for the HILIC method. For blank preparation, 50 µL of water was used and the same steps as described above were followed. |
Extract Storage: | -20℃ |
Combined analysis:
Analysis ID | AN004834 | AN004835 |
---|---|---|
Analysis type | MS | MS |
Chromatography type | HILIC | Reversed phase |
Chromatography system | Agilent 1260 Infinity II | Agilent 1260 Infinity II |
Column | Phenomenex Kinetex HILIC (150 x 2.1mm, 2.6um, 100Å) | Merck Supelco Ascentis Express C8 (150 x 2.1mm, 2.7um, 90Å) |
MS Type | ESI | ESI |
MS instrument type | Triple quadrupole | Triple quadrupole |
MS instrument name | Agilent 6470 QQQ | Agilent 6470 QQQ |
Ion Mode | POSITIVE | UNSPECIFIED |
Units | Areas | Areas |
Chromatography:
Chromatography ID: | CH003653 |
Chromatography Summary: | Used to detect small polar metabolites (adenosine, betaine, L-carnitine d3, cortisol, creatine, creatinine, hexanoylcarnitine, hippuric acid hypoxanthine, L-isoleucine d7, L-arginine, L-carnitine, L-leucine/isoleucine, L-phenylalanine, L-phenylalanine d5, L-proline, propionylcarnitine, urea, and valine d8). To achieve metabolite separation, a gradient elution on a Kinetex HILIC (150 mm × 2.1 mm × 100 Å) column maintained at 25 °C was used. The mobile phases consisted of (A) water, and (B) ACN, both with 7.5 mM ammonium acetate and 0.1% acetic acid, obtaining a final pH of 4.0 in the aqueous phase. The flow rate was 0.5 mL/min. The gradient started with 5% of A for 2 min, then increased up to 50% until 12 min, and back to initial conditions until 22 min. |
Instrument Name: | Agilent 1260 Infinity II |
Column Name: | Phenomenex Kinetex HILIC (150 x 2.1mm, 2.6um, 100Å) |
Column Temperature: | 25ºC |
Flow Gradient: | The gradient started with 5% of A for 2 min, then increased up to 50% until 12 min, and back to initial conditions until 22 min. |
Flow Rate: | 0.5mL/min |
Solvent A: | 100% water; 0.1% acetic acid; 7.5mm ammonium acetate |
Solvent B: | 100% acetonitrile; 0.1% acetic acid; 7.5mm ammonium acetate |
Chromatography Type: | HILIC |
Chromatography ID: | CH003654 |
Chromatography Summary: | To detect metabolites with medium polarity (arachidonic acid, bilirubin, lactic acid, lauric acid, LPC 14:0, LPC 16:0, LPC 17:0, LPC 17:1, LPC 18:0, LPC 18:1, LPC 18:1 d7, LPC 19:0, LPC 20:0, LPE 18:0, LPI 20:4, oleic acid, palmitic acid d31, palmitoleic acid, sphingosine, sphingosine d7, and S1P). For metabolite separation, a gradient elution on a Supelco Ascentis Express reversed-phase (150 mm × 2.1 mm × 2.7 μm) column maintained at 60 °C was used. The mobile phases consisted of (A) water, and (B) ACN, both with 0.1% acetic acid, obtaining a final pH of 3.3 in the aqueous phase. The flow rate was 0.6 mL/min. The gradient started with 20% of B for 2 min, then increased up to 100% until 10 min and maintained for 5 min, then returned to initial conditions until 20 min. |
Instrument Name: | Agilent 1260 Infinity II |
Column Name: | Merck Supelco Ascentis Express C8 (150 x 2.1mm, 2.7um, 90Å) |
Column Temperature: | 60ºC |
Flow Gradient: | The gradient started with 20% of B for 2 min, then increased up to 100% until 10 min and maintained for 5 min, then returned to initial conditions until 20 min. |
Flow Rate: | 0.6mL/min |
Solvent A: | 100% water; 0.1% acetic acid |
Solvent B: | 100% acetonitrile; 0.1% acetic acid |
Chromatography Type: | Reversed phase |
MS:
MS ID: | MS004580 |
Analysis ID: | AN004834 |
Instrument Name: | Agilent 6470 QQQ |
Instrument Type: | Triple quadrupole |
MS Type: | ESI |
MS Comments: | The MS conditions were as follows: 5500 V of capillary voltage in positive ESI mode, a nebulizer gas flow rate of 11.0 L/min, a source temperature of 250 °C; and a source pressure of 60 psi. Chromatogram visualization and peak areas were obtained using MassHunter Workstation B.05.00 and MassHunter QQQ Quantitative Analysis B.08.00, respectively. |
Ion Mode: | POSITIVE |
MS ID: | MS004581 |
Analysis ID: | AN004835 |
Instrument Name: | Agilent 6470 QQQ |
Instrument Type: | Triple quadrupole |
MS Type: | ESI |
MS Comments: | The MS was done with polarity switching with the following conditions: 3500 V of capillary voltage in positive ESI mode and 3000V in negative ESI mode, a nebulizer gas flow rate of 10.0 L/min, a source temperature of 250 °C; and a source pressure of 45 psi. Chromatogram visualization and peak areas were obtained using MassHunter Workstation B.05.00 and MassHunter QQQ Quantitative Analysis B.08.00, respectively. |
Ion Mode: | UNSPECIFIED |