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| Name | Class |
|---|---|
| Chinese University of Hong Kong | OTHER |
| Stanford University | OTHER |
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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.](streamdown:incomplete-link)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| urticaria | Patients with this condition | ||
| asthma | Patients with this condition | ||
| eczema | Patients with this condition | ||
| food allergy | Patients with this condition | ||
| anaphylaxis | Patients with this condition | ||
| mastocytosis | Patients with this condition | ||
| mast cell activating syndrome | Patients with this condition |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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 | 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 | 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. | 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. |
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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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Highly allergic individuals
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| Name | Affiliation | Role |
|---|---|---|
| Tak H Lee | Hong Kong Sanatorium and Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hong Kong Sanatorium & Hospital | Hong Kong | Hong Kong |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27628164 | Background | 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. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Validation Group | Mast cell activation test employing normal donor cultured mast cells and allergic patient serum samples |
| FG001 | SH#1 | Male patient, Total IgE: 28918KU/L; Der p2IgE: 64.4KU/L; clinical diagnosis: Eczema |
| FG002 | SH#2 | Male patient, Total IgE: 22311KU/L; Der p2IgE: 91.24KU/L; clinical diagnosis: Eczema |
| FG003 | SH#3 | Female patient, Total IgE: 5333KU/L; Der p2IgE: >100KU/L; clinical diagnosis: Eczema |
| FG004 | SH#4 | Male patient, Total IgE: 4070KU/L; Der p2IgE: >100KU/L; clinical diagnosis: Eczema, Urticaria |
| FG005 | SH#5 | Male patient, Total IgE: 379KU/L; Der p2IgE: 0.15KU/L; clinical diagnosis: Exercise-induced anaphylaxis |
| FG006 | SH#6 | Female patient, Total IgE: 13KU/L; Der p2IgE: <0.1KU/L; clinical diagnosis: Mast cell activation syndrome |
| FG007 | SH#7 | Male patient, Total IgE: 67KU/L; Der p2IgE: None KU/L; clinical diagnosis: Urticaria |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
During recruitment period, no participants with asthma, food allergy, mastocytosis were recruited.
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| ID | Title | Description |
|---|---|---|
| BG000 | Validation Group | Mast cell activation test employing normal donor cultured mast cells and allergic patient serum samples |
| BG001 | SH#1 | Male patient, Total IgE: 28918KU/L; Der p2IgE: 64.4KU/L; clinical diagnosis: Eczema |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Mast cells were cultured from blood of normal donors to validate the (Mast Cell Activation) MAT assay. The serum samples were obtained from allergic patients with sensitivities to Der p2 and used for passive sensitization of normal donor mast cells followed by their activation by Der p2 allergen. Data were collected only from the validation group. | Posted | Count of Participants | Participants | Mast cells studied after 9 weeks in culture |
|
18 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Validation Group | Mast cell activation test employing normal donor cultured mast cells and allergic patient serum samples |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Tak Hong Lee | Hong Kong Sanatorium & Hospital | 28358430 | TakHong.Lee@hksh.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 21, 2017 | Feb 10, 2020 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Nov 1, 2017 | Feb 10, 2020 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| D008415 | Mastocytosis |
| D000090267 | Mast Cell Activation Syndrome |
| D005512 | Food Hypersensitivity |
| D000080223 | Chronic Urticaria |
| D000707 | Anaphylaxis |
| D004485 | Eczema |
| D006967 | Hypersensitivity |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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blood samples for mediator measurements
| Mast cells studied after 9 weeks in culture |
| BG002 | SH#2 | Male patient, Total IgE: 22311KU/L; Der p2IgE: 91.24KU/L; clinical diagnosis: Eczema |
| BG003 | SH#3 | Female patient, Total IgE: 5333KU/L; Der p2IgE: >100KU/L; clinical diagnosis: Eczema |
| BG004 | SH#4 | Male patient, Total IgE: 4070KU/L; Der p2IgE: >100KU/L; clinical diagnosis: Eczema, Urticaria |
| BG005 | SH#5 | Male patient, Total IgE: 379KU/L; Der p2IgE: 0.15KU/L; clinical diagnosis: Exercise-induced anaphylaxis |
| BG006 | SH#6 | Female patient, Total IgE: 13KU/L; Der p2IgE: <0.1KU/L; clinical diagnosis: Mast cell activation syndrome |
| BG007 | SH#7 | Male patient, Total IgE: 67KU/L; Der p2IgE: None KU/L; clinical diagnosis: Urticaria |
| BG008 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Clinical diagnosis | Clinical diagnosis of participants before Mast cell activation test | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | 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. | Serum samples were obtained from 19 patients in total, of whom 12 were in the validation group. The other 7 patients were studied more extensively in the trial and their data is reported individually in this section and thereafter. | Posted | Count of Participants | Participants | Mast cells studied after 9 weeks in culture |
|
|
|
| Primary | 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 | Mast cells derived from the validation group is reported as a group (mean +/-SD). The other 7 allergic patients were analysed and reported individually as explained earlier. | Posted | Mean | Standard Deviation | percentage of histamine released | Mast cells studied after 9 weeks in culture |
|
|
|
| Primary | 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 | Mast cells derived from 7 allergic patients were analysed and reported individually. Patients in the validation group were not measured for this outcome and their samples were only used to validate the assay. | Posted | Number | percentage of histamine release | Mast cells studied after 9 weeks in culture |
|
|
|
| Primary | 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. | Mast cells derived from 7 allergic patients were analysed and reported individually. Patients in the validation group were not measured for this outcome and their samples were only used to validate the assay. | Posted | Number | percentage of histamine release | Mast cells studied after 9 weeks in culture |
|
|
|
| Primary | 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. | Mast cells derived from 7 allergic patients were analysed and reported individually. Patients in the validation group were not measured for this outcome and their samples were only used to validate the assay. | Posted | Number | Cell yield per 100ml blood | Mast cells studied after 9 weeks in culture |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | SH#1 | Male patient, Total IgE: 28918KU/L; Der p2IgE: 64.4KU/L; clinical diagnosis: Eczema | 0 | 1 | 0 | 1 | 0 | 1 |
| EG002 | SH#2 | Male patient, Total IgE: 22311KU/L; Der p2IgE: 91.24KU/L; clinical diagnosis: Eczema | 0 | 1 | 0 | 1 | 0 | 1 |
| EG003 | SH#3 | Female patient, Total IgE: 5333KU/L; Der p2IgE: >100KU/L; clinical diagnosis: Eczema | 0 | 1 | 0 | 1 | 0 | 1 |
| EG004 | SH#4 | Male patient, Total IgE: 4070KU/L; Der p2IgE: >100KU/L; clinical diagnosis: Eczema, Urticaria | 0 | 1 | 0 | 1 | 0 | 1 |
| EG005 | SH#5 | Male patient, Total IgE: 379KU/L; Der p2IgE: 0.15KU/L; clinical diagnosis: Exercise-induced anaphylaxis | 0 | 1 | 0 | 1 | 0 | 1 |
| EG006 | SH#6 | Female patient, Total IgE: 13KU/L; Der p2IgE: <0.1KU/L; clinical diagnosis: Mast cell activation syndrome | 0 | 1 | 0 | 1 | 0 | 1 |
| EG007 | SH#7 | Male patient, Total IgE: 67KU/L; Der p2IgE: None KU/L; clinical diagnosis: Urticaria | 0 | 1 | 0 | 1 | 0 | 1 |
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D007154 | Immune System Diseases |
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D000090362 | Mast Cell Activation Disorders |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003872 | Dermatitis |
| D017443 | Skin Diseases, Eczematous |