An observational study in Asthma, Mastocytosis and Mast Cell Activation Syndrome, sponsored by Hong Kong Sanatorium & Hospital. Completed at 1 site in Hong Kong. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-04-09.
Sponsored by Hong Kong Sanatorium & Hospital · Observational
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.
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.
Highly allergic individuals
Any patients with the above diagnoses -
Exclusion Criteria:
Children \< 18 years old; those who are unwilling or unable to donate blood; pregnant mothers.
-
Patients with this condition
Patients with this condition
Patients with this condition
Patients with this condition
Patients with this condition
Patients with this condition
Patients with this condition
Mast Cell Activation Test Results for Validation Group
Mast Cell Activation Test results of high/low level of house dust mite sensitivity by using normal donor cultured mast cells for validation.
Time frame: Mast cells studied after 9 weeks in culture
Evaluation of Patient's Serum for Autoreactivity on Normal Average Responder Mast Cell Activation
Patient's serum was incubated with mast cells derived from normal donors for detection of mast cell activation as evidenced by histamine release.
Time frame: Mast cells studied after 9 weeks in culture
Percentage Histamine Release by Normal Average Responder Mast Cells + Patient's Serum to Assess Autoreactivity
percentage of total histamine release by normal average responder mast cells that had been activated with patient's serum
Time frame: Mast cells studied after 9 weeks in culture
Percentage Histamine Release by Patient's Mast Cells + Immunoglobulin E (IgE)/Anti-IgE
percentage of total histamine release by patient's mast cells that had been activated with anti-IgE
Time frame: Mast cells studied after 9 weeks in culture
Percentage of Histamine Release by Patient's Mast Cells + Patient's Serum + Allergen
Percentage of total histamine release when patient's mast cells were activated with patient's own serum and Der p2. Each patient's results are reported individually.
Time frame: Mast cells studied after 9 weeks in culture
Cell Yield Per 100ml Blood
Cell yield of patient's mast cell culture after 9 weeks in culture as an index of cell growth and differentiation.
Time frame: Mast cells studied after 9 weeks in culture
19 patients were recruited in the study. 12 were used for validation. 7 were used for patient-specific testing. Therefore, there were 1 validation group and 7 individuals' result.
| Milestone | Validation Group | SH#1 | SH#2 | SH#3 | SH#4 | SH#5 | SH#6 | SH#7 |
|---|---|---|---|---|---|---|---|---|
| Started | 12 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
| Completed | 12 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Mast Cell Activation Test results of high/low level of house dust mite sensitivity by using normal donor cultured mast cells for validation.
| Participants | Validation Group |
|---|---|
| High level of house dust mite sensitivity — MAT positive | 6 |
| High level of house dust mite sensitivity — MAT negative | 2 |
| Low level of house dust mite sensitivity — MAT positive | 0 |
| Low level of house dust mite sensitivity — MAT negative | 4 |
Patient's serum was incubated with mast cells derived from normal donors for detection of mast cell activation as evidenced by histamine release.
| Participants | Validation Group | SH#1 | SH#2 | SH#3 | SH#4 | SH#5 | SH#6 | SH#7 |
|---|---|---|---|---|---|---|---|---|
| Evaluation of Patient's Serum for Autoreactivity on Normal Average Responder Mast Cell Activation | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
percentage of total histamine release by normal average responder mast cells that had been activated with patient's serum
| percentage of histamine released | Validation Group | SH#1 | SH#2 | SH#3 | SH#4 | SH#5 | SH#6 | SH#7 |
|---|---|---|---|---|---|---|---|---|
| Percentage Histamine Release by Normal Average Responder Mast Cells + Patient's Serum to Assess Autoreactivity | 2.15 ± 0.71 | 32.1 | 3.3 | 2.8 | 3.4 | 5.1 | 3.2 | 3.8 |
percentage of total histamine release by patient's mast cells that had been activated with anti-IgE
| percentage of histamine release | SH#1 | SH#2 | SH#3 | SH#4 | SH#5 | SH#6 | SH#7 |
|---|---|---|---|---|---|---|---|
| Percentage Histamine Release by Patient's Mast Cells + Immunoglobulin E (IgE)/Anti-IgE | 11.5 | 38.3 | 69.6 | 47.9 | 36.3 | 45.5 | 41.6 |
Percentage of total histamine release when patient's mast cells were activated with patient's own serum and Der p2. Each patient's results are reported individually.
| percentage of histamine release | SH#1 | SH#2 | SH#3 | SH#4 | SH#5 | SH#6 | SH#7 |
|---|---|---|---|---|---|---|---|
| Percentage of Histamine Release by Patient's Mast Cells + Patient's Serum + Allergen | 24.5 | 54.7 | 79 | 8.4 | 0.2 | 0.2 | 0 |
Cell yield of patient's mast cell culture after 9 weeks in culture as an index of cell growth and differentiation.
| Cell yield per 100ml blood | SH#1 | SH#2 | SH#3 | SH#4 | SH#5 | SH#6 | SH#7 |
|---|---|---|---|---|---|---|---|
| Cell Yield Per 100ml Blood | 14045000 | 2895522 | 115294 | 625263 | 4867778 | 352000 | 1400000 |
Collected over 18 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Validation Group | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) |
| SH#1 | 0/1 (0%) | 0/1 (0%) | 0/1 (0%) |
| SH#2 | 0/1 (0%) | 0/1 (0%) | 0/1 (0%) |
| SH#3 | 0/1 (0%) | 0/1 (0%) | 0/1 (0%) |
| SH#4 | 0/1 (0%) | 0/1 (0%) | 0/1 (0%) |
| SH#5 | 0/1 (0%) | 0/1 (0%) | 0/1 (0%) |
| SH#6 | 0/1 (0%) | 0/1 (0%) | 0/1 (0%) |
| SH#7 | 0/1 (0%) | 0/1 (0%) | 0/1 (0%) |
During recruitment period, no participants with asthma, food allergy, mastocytosis were recruited.
| Age, Categorical(Participants) | Validation Group | SH#1 | SH#2 | SH#3 | SH#4 | SH#5 | SH#6 | SH#7 | Total |
|---|---|---|---|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 12 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 19 |
| >=65 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Validation Group | SH#1 | SH#2 | SH#3 | SH#4 | SH#5 | SH#6 | SH#7 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Female | 9 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 11 |
| Male | 3 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 8 |
| Race (NIH/OMB)(Participants) | Validation Group | SH#1 | SH#2 | SH#3 | SH#4 | SH#5 | SH#6 | SH#7 | Total |
|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 12 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 18 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| White | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Validation Group | SH#1 | SH#2 | SH#3 | SH#4 | SH#5 | SH#6 | SH#7 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Hong Kong | 12 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 7 |
| Clinical diagnosis(Participants) | Validation Group | SH#1 | SH#2 | SH#3 | SH#4 | SH#5 | SH#6 | SH#7 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Eczema | 4 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 7 |
| Rhinitis | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 |
| Urticaria | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 4 |
| Exercise-induced anaphylaxis | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Mast cell activation syndrome | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Eczema and Urticaria | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
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Hong Kong Sanatorium & Hospital