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Allergy. 2018 Nov;73(11):2137-2149. doi: 10.1111/all.13563. Epub 2018 Aug 9.

Multi-omics analysis points to altered platelet functions in severe food-associated respiratory allergy.

Author information

1
IMMA, Instituto de Medicina Molecular Aplicada, Facultad de Medicina, Universidad San Pablo CEU, Madrid, España.
2
CEMBIO, Centro de Excelencia en Metabolómica y Bioanálisis, Facultad de Farmacia, Universidad San Pablo CEU, Madrid, España.
3
Departamento de Ciencias Médicas Clínicas, Facultad de Medicina, Universidad San Pablo CEU, Madrid, España.
4
Hospital Universitario HM Sanchinarro, Madrid, España.
5
Hospital Universitario Clínico San Carlos, Madrid, España.
6
Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, España.
7
Hospital Virgen del Puerto, Plasencia, Cáceres, España.
8
Departamento de Matemática Aplicada y Estadística, Universidad San Pablo CEU, Madrid, España.
9
Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad San Pablo CEU, Madrid, España.

Abstract

BACKGROUND:

Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation. Our aim was to identify the underlying mechanisms and the associated biomarkers of this progression, focusing on severe phenotypes, using transcriptomics and metabolomics.

METHODS:

Twenty-five subjects were included in the study. Plasma samples were analyzed using gas and liquid chromatography coupled to mass spectrometry (GC-MS and LC-MS, respectively). Individuals were classified in four groups-"nonallergic," "mild," "moderate," and "severe"-based on their clinical history, their response to an oral challenge test with profilin, and after a refinement using a mathematical metabolomic model. PBMCs were used for microarray analysis.

RESULTS:

We found a set of transcripts and metabolites that were specific for the "severe" phenotype. By metabolomics, a decrease in carbohydrates and pyruvate and an increase in lactate were detected, suggesting aerobic glycolysis. Other metabolites were incremented in "severe" group: lysophospholipids, sphingosine-1-phosphate, sphinganine-1-phosphate, and lauric, myristic, palmitic, and oleic fatty acids. On the other hand, carnitines were decreased along severity. Significant transcripts in the "severe" group were found to be downregulated and were associated with platelet functions, protein synthesis, histone modification, and fatty acid metabolism.

CONCLUSION:

We have found evidence that points to the association of severe allergic inflammation with platelet functions alteration, together with reduced protein synthesis, and switch of immune cells to aerobic glycolysis.

KEYWORDS:

food allergy; metabolomics; platelets; respiratory allergy; transcriptomics

PMID:
30028518
DOI:
10.1111/all.13563

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