Immunologic Deficiency Syndrome
Conditions
Keywords
Cytokine, Stat, Jak, IL-12, Mutation, Immunodeficiency
Brief summary
The purpose of this study is to evaluate patients with primary immunodeficiency disorders to identify patients with mutations of the genes for the following proteins: Jak3, STAT1, STAT4, interleukin-7, interleukin-7 receptor, interleukin-12 receptor subunits, and others. Patients will undergo screening history, physical examination, and clinical laboratory evaluation at referring institutions and tissue samples, or cell lines will be sent to the NIH. We will establish cell lines if necessary, prepare DNA and RNA for molecular genetic analysis and study cytokine signal transduction in patient cell lines.
Detailed description
The purpose of this study is to evaluate patients with primary immunodeficiency disorders to identify patients with mutations of the genes for the following proteins: Jak3, STAT1, STAT4, interleukin-7, interleukin-7 receptor, interleukin-12 receptor subunits, and others. Patients will undergo screening history, physical examination, and clinical laboratory evaluation at referring institutions and tissue samples, or cell lines will be sent to the NIH. We will establish cell lines if necessary, prepare DNA and RNA for molecular genetic analysis and study cytokine signal transduction in patient cell lines.
Interventions
None listed
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: Samples from patients with known or suspected primary immunodeficiencies, including those treated with stem cell transplants or gene correction therapy, and their families will be accepted worldwide primarily from tertiary care centers that treat patients with such immunodeficiencies. Such patients will have documented evidence of either opportunistic infection, recurrent infection, or unusually severe responses to infectious agents that cause mild illness in unaffected individuals. In selected cases, at the discretion of the investigators, samples for testing will be obtained from consenting adult relatives of affected individuals. Either patient-derived B cell lines or primary blood samples will be accepted although in some cases buccal swabs will also be accepted. Blood samples may be obtained from unaffected children. Additionally; patients with particularly interesting clinical presentations (e.g. adults with possible attenuated immunodeficiency) may be seen for outpatient visits at the NIH Clinical Center for evaluation. Infants with SCID or other primary immunodeficiency will not be seen; their physicians will care them for and only clinical material will be sent on such patients. Medically stable patients with mild to moderate immunodeficiency may be seen at the NIH. We will encourage the participation of women and members of minority groups in this study.
Exclusion criteria
Inability to provide informed consent. A presence of any medical condition that would, in the opinion of the investigators, confuse the interpretation of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Natural History of Immunologic Deficiency Syndrome | Enrollment with follow-up | The objectives of the study are: (1) To identify new patients with Jak3 deficiency to determine the range of mutations that occur, to study these mutations in in vitro assays and to relate these findings to the clinical presentation. We will also try to develop improved assays for the diagnosis of Jak3 deficiency. (2) To analyze the function of lymphoid and myeloid cells from patients who have undergone stem cell transplants for Jak3- and XSCID (3) To analyze patients with TB+SCID without mutations of Jak3 and c for mutations in IL- 7, IL-7 receptor genes. (4) To analyze patients with defects in cell-mediated immunity to try to identify patients with mutations of the genes encoding IL-12 subunits, IL-12 receptor subunits and the transcription factors Stat1, Stat 4 and IRF. |
Countries
United States
Outcome results
None listed