Evaluation of the Sphingolipid Metabolite S1P as a Novel Biomarker in Food Allergy

The Role of Sphingosine-1-phosphate in Food Allergy - Biomarker for Disease Severity and Anaphylaxis Outcome

Food allergies represent an increasing health concern in the industrialized countries and especially affect pediatric patients. In this population adverse reactions against food compounds can lead to anaphylactic reactions. Despite substantial research efforts, clinical markers predicting disease severity and symptoms are missing to date.

Recent studies have revealed that sphingolipids, especially sphingosine-1-phosphate (S1P), play an essential role in allergy. It was reported that asthmatic patients have higher S1P levels in bronchiallavage fluids after allergen challenge. First experimental studies revealed a correlation of S1P and the outcome of anaphylaxis. Furthermore, we have shown in our recent mouse study that S1P homeostasis is pivotal for food allergy induction and effector cell response. Therefore, it is the aim of the presented pilot project to evaluate whether S1P serum titers are altered in food allergic children and if the S1P levels correlate with the outcome of anaphylaxis during double blind placebo controlled food challenges (DBPCFCs).

Study Overview

• Status: Unknown
• Conditions: Food Allergy; Anaphylaxis

• Study Type: Observational
• Enrollment (Anticipated): 70

Contacts and Locations

• Study Contact: Name: Zsolt Szépfalusi, MD; Phone Number: 3232 +43 1 40400; Email: zsolt.szepfalusi@meduniwien.ac.at
• Study Contact Backup: Name: Susanne C. Diesner, MD, PhD; Phone Number: +43 1 40400; Email: susanne.diesner@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University Vienna, Department of Pediatrics and Adolescent Medicine
    • Principal Investigator: Zsolt Szépfalusi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children (age 1-17 years) being in medical care at the allergy clinic of the Department of Pediatrics and Adolescent Medicine of the Medical University of Vienna for food related immediate type symptoms (nausea, abdominal pain, vomiting, diarrhea or local symptoms like burning, swelling, itching and erythema) immediately after ingestion of food compounds will be enrolled in this study.

Description

Inclusion Criteria:

• Patients between 1-17 years who have been reported to suffer from food allergic reactions and who are subjected to DBPCFC or open provocation
• Patients who are diagnosed by elevated allergen specific IgE and/or positive skin prick testing
• Willingness to participate in the study

Exclusion Criteria:

• Refusal to participate in the study
• Non-IgE-mediated food allergy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
food allergic; positive reaction during DBPCFC
Non-food allergic; no reaction during DBPCFC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
S1P in allergic and non-allergic patients before and after challenge	The primary endpoint of this study is the measurement of S1P in allergic and non-allergic patients before and after challenge.	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of allergic mediators and correlation with S1P levels	Evaluation of allergic mediators like histamine, human mast cell tryptase and eosinophil cationic protein and correlate these results with the levels of S1P within the group and between allergic and non-allergic patients	up to 3 years

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Eva Untersmayr-Elsenhuber, MD, PhD, Medical University Vienna, Department of Pathophysiology and Allergy Research

Publications and helpful links

General Publications

• Diesner SC, Olivera A, Dillahunt S, Schultz C, Watzlawek T, Forster-Waldl E, Pollak A, Jensen-Jarolim E, Untersmayr E, Rivera J. Sphingosine-kinase 1 and 2 contribute to oral sensitization and effector phase in a mouse model of food allergy. Immunol Lett. 2012 Jan 30;141(2):210-9. doi: 10.1016/j.imlet.2011.10.006. Epub 2011 Oct 14. Erratum In: Immunol Lett. 2012 Aug 30;146(1-2):79.
• Olivera A, Eisner C, Kitamura Y, Dillahunt S, Allende L, Tuymetova G, Watford W, Meylan F, Diesner SC, Li L, Schnermann J, Proia RL, Rivera J. Sphingosine kinase 1 and sphingosine-1-phosphate receptor 2 are vital to recovery from anaphylactic shock in mice. J Clin Invest. 2010 May;120(5):1429-40. doi: 10.1172/JCI40659. Epub 2010 Apr 19.
• Olivera A, Mizugishi K, Tikhonova A, Ciaccia L, Odom S, Proia RL, Rivera J. The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis. Immunity. 2007 Mar;26(3):287-97. doi: 10.1016/j.immuni.2007.02.008. Epub 2007 Mar 8.
• Ammit AJ, Hastie AT, Edsall LC, Hoffman RK, Amrani Y, Krymskaya VP, Kane SA, Peters SP, Penn RB, Spiegel S, Panettieri RA Jr. Sphingosine 1-phosphate modulates human airway smooth muscle cell functions that promote inflammation and airway remodeling in asthma. FASEB J. 2001 May;15(7):1212-4. doi: 10.1096/fj.00-0742fje. No abstract available.

Helpful Links

• study center
• study center
• project homepage

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Anticipated): January 1, 2017
• Study Completion (Anticipated): January 1, 2017

Study Registration Dates

• First Submitted: January 21, 2013
• First Submitted That Met QC Criteria: January 23, 2013
• First Posted (Estimate): January 28, 2013

Study Record Updates

• Last Update Posted (Estimate): December 11, 2015
• Last Update Submitted That Met QC Criteria: December 9, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Biomarker; Anaphylaxis; Food allergy; Sphingosine-1-phosphate; Double-blind placebo-controlled food challenge
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity; Anaphylaxis
• Other Study ID Numbers: 119/2011; KLI 284-B00 (Other Grant/Funding Number: Austria Science Fund)