Mechanisms of Immune Deficiency
Trial Snapshot
- Phase
- Not Applicable
- Enrollment
- 200
- Locations
- 1
- Primary Endpoint
- Measurement of Serum immune globulin
Study Overview
Brief Summary
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The purpose of this study is to learn more about the changes in genes, cells and proteins that cause immune deficiency diseases.
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The early stages of the study will focus on two groups of patients:
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members of families in which several persons have symptoms or medical histories that suggest immune deficiency.
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Patients who have received treatments with medications or drugs that affect functions of the immune system (secondary immune deficiencies).
It is hoped that studies will provide guidelines for extension of the research to other patient groups. Up to 200 patients and family members will be invited to participate.
Detailed Description
The experiments that are proposed in this portion of the study are intended to:
- characterize the significance of the variant form of EZH2 identified in this family. They will characterize the degree of methylation of lysine 27 of histone H3 in subjects with the variant and members of the same family who have the wild type gene. The functional methyltransferase activity of the variant and wild type genes will be measured.
- characterize the current status of B-cell maturation and function in subjects with either the variant gene and the wild type gene.
- characterize B-cell function (antibody production) and the quality of antibody produced after immunizations in subjects with the wild type gene or the variant gene.
Study Design
- Study Type
- Observational
- Observational Model
- Family Based
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 99 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Immunodeficiency disease; or
- •family member of individual with immunodeficiency disease
Exclusion Criteria
- •Persons with immune deficiencies that are secondary to other diseases such as malignancies.
- •Persons who do not have immune deficiencies, persons who are not meet eligibility criteria
Outcomes
Primary Outcomes
Measurement of Serum immune globulin
Time Frame: each year for up to 20 years
The clinical definition of "hypogamma-globulinemia is values that are 2 SD below the mean value for the testing laboratory. For this study values that are below the lower limit of abnormal will be scored as abnormal. Chi-square analysis or Fisher's exact test will compare values between subjects with the wild type gene and the variant gene.
Antibody responses
Time Frame: 4 weeks
A four-fold difference or a post-immunization titer of ≥1.3 µg/ml is scored as a true antibody response. Antibody titers and avidity indices are transformed to log2 and evaluated using the Student's T-test.
measurement of cellular components of the immune system
Time Frame: each year for up to 20 years
Flow cytometry will be used to identify numbers of cells of various types (e.g.,subpopulations of B-cells and T-cells) to evaluate changes in various cell populations over time. This is especially important for studies of family members who carry disease-causing or disease-associated genes but are clinically health at the time of the first study
Measurement of avidity
Time Frame: each year for up to 20 years
avidity indices are transformed to log2 and evaluated using the Student's T-test
health outcome measurements
Time Frame: each year for up to 20 years
The SF-36 form will be used serially to identify changes in health over time
Measurement of NK cell function
Time Frame: one time
Spearman correlation will be used to compare the relationship between expression of CD207a by NK cells that are activated with K562 cells or NK cells that are activated with PMA/iono.
DNA sequencing
Time Frame: one time
When indicated, whole exome or whole genome sequencing will be done to identify genetic basis (if any) of the immune deficiency
Secondary Outcomes
No secondary outcomes reported