Open AccessGene-Metabolite Expression in Blood Can Discriminate Allergen-Induced Isolated Early from Dual Asthmatic Responses
Author(s) -
Amrit Singh,
Masatsugu Yamamoto,
Sarah Kam,
Jian Ruan,
Gail Gauvreau,
Paul M. O'Byrne,
J. Mark FitzGerald,
R. Robert Schellenberg,
LouisPhilippe Boulet,
Gabriella Wojewodka,
Cynthia Kanagaratham,
Juan B. De Sanctis,
Danuta Radzioch,
Scott J. Tebbutt
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0067907
Subject(s) - docosahexaenoic acid , metabolomics , immunology , fatty acid metabolism , arachidonic acid , fexofenadine , allergen , lipid metabolism , metabolome , transcriptome , medicine , lipidomics , allergy , biology , gene expression , pharmacology , fatty acid , metabolism , biochemistry , gene , bioinformatics , polyunsaturated fatty acid , enzyme
Some asthmatic individuals undergoing allergen inhalation challenge develop an isolated early response whereas others develop a dual response (early plus late response). In the present study we have used transcriptomics (microarrays) and metabolomics (mass spectrometry) of peripheral blood to identify molecular patterns that can discriminate allergen-induced isolated early from dual asthmatic responses. Peripheral blood was obtained prior to (pre-) and 2 hours post allergen inhalation challenge from 33 study participants. In an initial cohort of 14 participants, complete blood counts indicated significant differences in neutrophil and lymphocyte counts at pre-challenge between early and dual responders. At post-challenge, significant genes ( ALOX15 , FADS2 and LPCAT2 ) and metabolites (lysolipids) were enriched in lipid metabolism pathways. Enzymes encoding for these genes are involved in membrane biogenesis and metabolism of fatty acids into pro-inflammatory and anti-inflammatory mediators. Correlation analysis indicated a strong negative correlation between ALOX15 , FADS2 , and IL5RA expression with 2-arachidonoylglycerophosphocholine levels in dual responders. However, measuring arachidonic acid and docosahexaenoic acid levels in a validation cohort of 19 participants indicated that the free form of DHA (nmoles/µg of protein) was significantly (p = 0.03) different between early and dual responders after allergen challenge. Collectively these results may suggest an imbalance in lipid metabolism which dictates pro- (anti-) inflammatory and pro-resolving mechanisms. Future studies with larger sample sizes may reveal novel mechanisms and therapeutic targets of the late phase asthmatic response.