Clinical trial NCT03406325: Mast Cell Activation Test in Allergic Disease
Official title: Assessment of Mast Cell Activation Diagnostic Test in Patients With Allergic Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Mastocytosis
Mast Cell Activation Syndrome
Food Allergy
Chronic Idiopathic Urticaria
Anaphylaxis
Eczema
Keywords: mast cell
allergy
genomic
biomarkers
Lead sponsor: Hong Kong Sanatorium & Hospital
Sponsor class: INDUSTRY
Collaborators: name: Chinese University of Hong Kong
name: Stanford University
First posted: 2018-01-23
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Highly allergic individuals

Brief summary: Activation of mast cells in the immune system is known to cause allergic reactions sometimes with severe systemic symptoms. The investigators have recently developed a blood-based mast cell activation diagnostic test in which levels of functional activation in-vitro in primary cultured mast cells generated from the peripheral blood of single individuals can be assessed. It is the hypothesis that the test can be used to predict the potential state of in-vivo mast cell activation in any individual based on the functional activation profiles exhibited by their cultured mast cells. The investigators now wish to translate their in-vitro findings in a pilot study to disease groups where mast cell activation is expected to be high. These include highly allergic individuals; those with chronic idiopathic urticaria; those with mastocytosis; and those with the mast cell activation syndrome. Furthermore, they will use the functional genomics approach to identify gene expression biomarkers that are correlated with such diseases. The results will be compared with data that have been collected from a cohort of healthy control blood donors.

Detailed description: The objective of this study is to assess whether patients with severe allergic diseases exhibit high levels of mast cell activation as determined by the mast cell activation diagnostic test the investigators have developed. They anticipate that patients with history of severe allergic reactions will show up as high responders in the blood-based mast cell activation diagnostic test. Moreover, using microarray analysis as the approach for gene expression studies, they anticipate further that genomics biomarkers that are correlated with the high functional activation of the in-vitro mast cells derived from these patients can be readily identified.

About 100 ml of peripheral venous blood from individual patients will be drawn into heparinized syringes and collected in a blood-collecting bag/tube containing silica. The bag/tube will be promptly processed for the generation of primary human mast cell cultures using the protocol that has previously been developed \[Inflammation Research 66: 25 (2017). After culturing for 9 weeks, the resulting human mast cells will be analyzed for both their functional activity in terms of histamine release in response to the activation of high-affinity Immunoglobulin E (IgE) receptors in these cells and their gene expression profiles using microarray analysis. The in-vitro functional and genomics data will be correlated with specific diagnoses and measurements of blood prostaglandin D2 (PGD2), PGD2 metabolites, tryptase and histamine levels in blood. For mediator assays, plasma from each subject will be collected after the cluster of differentiation 34 positive (CD34+) isolation step and the samples will be aliquoted and frozen at -80 degrees centigrade for subsequent analysis.

Eligibility criteria: Inclusion Criteria:

Any patients with the above diagnoses -

Exclusion Criteria:

Children \< 18 years old; those who are unwilling or unable to donate blood; pregnant mothers.

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Primary outcomes:
measure: Mast Cell Activation Test Results for Validation Group
timeFrame: Mast cells studied after 9 weeks in culture
measure: Evaluation of Patient's Serum for Autoreactivity on Normal Average Responder Mast Cell Activation
timeFrame: Mast cells studied after 9 weeks in culture
measure: Percentage Histamine Release by Normal Average Responder Mast Cells + Patient's Serum to Assess Autoreactivity
timeFrame: Mast cells studied after 9 weeks in culture
measure: Percentage Histamine Release by Patient's Mast Cells + Immunoglobulin E (IgE)/Anti-IgE
timeFrame: Mast cells studied after 9 weeks in culture
measure: Percentage of Histamine Release by Patient's Mast Cells + Patient's Serum + Allergen
timeFrame: Mast cells studied after 9 weeks in culture
measure: Cell Yield Per 100ml Blood
timeFrame: Mast cells studied after 9 weeks in culture
Secondary outcomes:
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Hong Kong Sanatorium & Hospital
Study officials:
affiliation: Hong Kong Sanatorium and Hospital
name: Tak H Lee
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tam IYS, Ng CW, Tam SY, Lau HYA. Novel six-week protocol for generating functional human connective tissue-type (MCTC) mast cells from buffy coats. Inflamm Res. 2017 Jan;66(1):25-37. doi: 10.1007/s00011-016-0989-z. Epub 2016 Sep 15.