Developing Newborn Screening for Infants With Primary Immunodeficiency
| Status: | Completed |
|---|---|
| Conditions: | Infectious Disease, HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 4/21/2016 |
| Start Date: | June 2005 |
| End Date: | April 2007 |
This study will explore screening for immunodeficiency diseases (diseases that cause
problems in fighting infections). There is no method at present to screen all babies at
birth for immunodeficiency. However, babies with low numbers of T-cells-an important type of
immune system cell-may be found by studying T-cell products called TRECs (T-cell receptor
excision circles). This study will:
- Collect samples from children with several different immunodeficiencies to find out
which disorders can be found by screening dried blood spots for TRECs.
- Try to develop screening tests based on other kinds of material derived from dried
blood spots.
Children with primary immunodeficiency and low numbers of T cells who have not had a bone
marrow transplant may be eligible for this study.
Participating children donate up to 5 ml (1 teaspoon) of blood. The sample may be collected
when the child is having other blood tests. The liquid blood is analyzed to determine the
number of T cells, and the rest of the blood is used to make dried blood spots on filter
paper. The blood spots are used to develop screening tests for immunodeficiency. The blood
spots and data about the child's age, diagnosis, and current medicines will be kept coded by
diagnosis and a code number instead of the child's name.
problems in fighting infections). There is no method at present to screen all babies at
birth for immunodeficiency. However, babies with low numbers of T-cells-an important type of
immune system cell-may be found by studying T-cell products called TRECs (T-cell receptor
excision circles). This study will:
- Collect samples from children with several different immunodeficiencies to find out
which disorders can be found by screening dried blood spots for TRECs.
- Try to develop screening tests based on other kinds of material derived from dried
blood spots.
Children with primary immunodeficiency and low numbers of T cells who have not had a bone
marrow transplant may be eligible for this study.
Participating children donate up to 5 ml (1 teaspoon) of blood. The sample may be collected
when the child is having other blood tests. The liquid blood is analyzed to determine the
number of T cells, and the rest of the blood is used to make dried blood spots on filter
paper. The blood spots are used to develop screening tests for immunodeficiency. The blood
spots and data about the child's age, diagnosis, and current medicines will be kept coded by
diagnosis and a code number instead of the child's name.
Study Objective: T cell receptor excision circles (TRECs) are episomal DNA circles excised
from the T cell receptor genes during T cell maturation in the thymus. They do not
replicate, so they are diluted out as T cells proliferate. Our objectives are to examine the
levels of TRECs in blood samples from patients with primary immunodeficiency (PI) diseases;
to determine which PI diseases might be detected by testing newborn dried blood spots for
low numbers of TRECs; and to use the blood spots collected for future confirmatory or
alternative tests to develop newborn screening for PIs.
Population: Patients diagnosed with defined primary T cell immunodeficiency diseases or
undefined conditions with very low T cell numbers. There are several known, and additional
unknown, gene defects that impair T lymphocyte maturation and function. The frequency of
these rare disorders is unknown, but could potentially be learned in the course of
population-based newborn screening.
Design: We will contact our network of immunology colleagues to help us identify and enroll
patients already diagnosed with PI disorders. These patients will have had HIV ruled out as
part of their immune evaluation. We will provide mail-in kits and will receive blood samples
for analysis. We will attempt to retrieve the actual Guthrie cards containing the dried
blood spots of these patients from their state screening laboratories to determine the
number of TRECs that were present at birth in infants with these conditions.
Outcome Measures: We will measure TRECs in dried blood spots, and correlate TREC number with
diagnosis and clinical and laboratory data. We hope to determine the range of
immunodeficiency diseases that can be demonstrated to have significantly reduced TRECs as
compared to healthy subjects using our assay. Because TREC testing may be insufficiently
sensitive or specific as a stand-alone test, further tests may be developed and performed on
the samples in the future, including DNA re-sequencing, detection of mRNA for T cell
specific genes and/or proteins expressed only in T cells.
from the T cell receptor genes during T cell maturation in the thymus. They do not
replicate, so they are diluted out as T cells proliferate. Our objectives are to examine the
levels of TRECs in blood samples from patients with primary immunodeficiency (PI) diseases;
to determine which PI diseases might be detected by testing newborn dried blood spots for
low numbers of TRECs; and to use the blood spots collected for future confirmatory or
alternative tests to develop newborn screening for PIs.
Population: Patients diagnosed with defined primary T cell immunodeficiency diseases or
undefined conditions with very low T cell numbers. There are several known, and additional
unknown, gene defects that impair T lymphocyte maturation and function. The frequency of
these rare disorders is unknown, but could potentially be learned in the course of
population-based newborn screening.
Design: We will contact our network of immunology colleagues to help us identify and enroll
patients already diagnosed with PI disorders. These patients will have had HIV ruled out as
part of their immune evaluation. We will provide mail-in kits and will receive blood samples
for analysis. We will attempt to retrieve the actual Guthrie cards containing the dried
blood spots of these patients from their state screening laboratories to determine the
number of TRECs that were present at birth in infants with these conditions.
Outcome Measures: We will measure TRECs in dried blood spots, and correlate TREC number with
diagnosis and clinical and laboratory data. We hope to determine the range of
immunodeficiency diseases that can be demonstrated to have significantly reduced TRECs as
compared to healthy subjects using our assay. Because TREC testing may be insufficiently
sensitive or specific as a stand-alone test, further tests may be developed and performed on
the samples in the future, including DNA re-sequencing, detection of mRNA for T cell
specific genes and/or proteins expressed only in T cells.
- INCLUSION CRITERIA:
Patient who has not yet received a BMT and who has defined PI or undefined PI with T cell
lymphopenia.
EXCLUSION CRITERIA:
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