Allergy Asthma Immunol Res.  2019 May;11(3):330-342. 10.4168/aair.2019.11.3.330.

Altered Sphingolipid Metabolism Is Associated With Asthma Phenotype in House Dust Mite-Allergic Patients

• Kowal K
• Å»ebrowska E
• Chabowski

• KMID: 2442045
• DOI: http://doi.org/10.4168/aair.2019.11.3.330

Abstract

PURPOSE
Sphingolipids play an important role in cell growth, survival, inflammation and tissue remodeling. House dust mite (HDM) allergy is a major risk factor for asthma. The aim of the study was to evaluate if allergic asthma phenotype is associated with altered sphingolipid metabolism.
METHODS
Twenty-two HDM-allergic asthmatic patients and 11 HDM-allergic rhinitis patients were challenged intrabronchially with biologically standardized Dermatophagoides pteronyssinus extract. Whole blood and platelet-poor plasma samples were collected before, during early asthmatic response (EAR), late asthmatic response (LAR) and 24 hours after the challenge. Concentrations of sphinganine (SFA), sphinganine-1-phosphate (SFA1P), ceramide, sphingosine (SFO) and sphingosine-1-phosphate (S1P) were measured using high performance liquid chromatography.
RESULTS
In all house dust mite-allergic patients (HDM-APs), baseline lung function and severity of airway hyperreactivity (AHR) correlated significantly with plasma S1P and SFA1P concentrations. Exhaled nitric oxide concentration, however, correlated with SFA and ceramide, but not with S1P or SFA1P concentration. Allergen challenge increased plasma S1P concentration during EAR, but only in patients who developed both EAR and LAR. The magnitude of the increase determined during EAR correlated with the severity of subsequently developed LAR. Platelet and eosinophil counts were independent predictors of plasma S1P concentration. A significant increase in plasma SFA concentration in response to allergen challenge was seen only in patients who did not develop asthmatic response.
CONCLUSIONS
Altered sphingolipid metabolism, with augmented synthesis of S1P and impaired de novo sphingolipid synthesis in response to allergen challenge, may participate in the development of asthma phenotype in HDM-APs.

Keyword

Lipid mediators; asthma; inflammation

MeSH Terms

Asthma*
Blood Platelets
Chromatography, Liquid
Dermatophagoides pteronyssinus
Dust*
Ear
Eosinophils
Humans
Hypersensitivity
Inflammation
Lung
Metabolism*
Nitric Oxide
Phenotype*
Plasma
Pyroglyphidae
Rhinitis
Risk Factors
Sphingolipids
Sphingosine
Dust
Nitric Oxide
Sphingolipids
Sphingosine

Figure

• 

  Fig. 1 Plasma concentrations of selected sphingolipids in relation to the severity of AHR in HDM-APs. PC20 ≤ 4; patients with histamine PC20 equal to or less than 4 mg/mL; PC20 > 4; patients with histamine PC20 greater than 4 mg/mL. Only significant differences were indicated. AHR, airway hyperreactivity; HDM-AP, house dust mite-allergic patient; PC20, histamine concentration causing 20% fall in forced expiratory volume in 1 second.

• 

  Fig. 2 Changes in plasma S1P (A, B and C) and SFA (D, E and F) concentrations during allergen challenge in dual responders (A and D), single responders (B and E) and non-responders (C and F). S1P, sphingosine-1-phosphate; SFO, sphingosine; SFA, sphinganine; SFA1P, sphinganine-1-phosphate. *Significantly greater than at baseline; †significantly less than at baseline.

• 

  Fig. 3 Correlations between changes in plasma S1P concentration during EAR and the severity of subsequent LAR. S1P, sphingosine-1-phosphate; EAR, early asthmatic response; LAR, late asthmatic response.

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