This study will determine the biochemical and genetic causes of inherited immune diseases affecting lymphocyte homeostasis. Lymphocytes are a type of white blood cell that fights infections. Normally, the body keeps a precise balance in which lymphocyte growth is matched by lymphocyte death. People with constantly enlarged lymph nodes or spleen, along with autoimmune disease, immunodeficiency, lymphoma, or other immune problems affecting lymphocytes may have an abnormality of the immune system in the cell growth and cell death processes that regulate lymphocyte homeostasis.
Patients who have, or are suspected of having, an inherited lymphocyte homeostasis or programmed cell death susceptibility syndrome may be eligible for this study. Relatives of patients are also included.
Participants' (patients and relatives) medical records are reviewed and blood samples are drawn for studies to identify genes involved in immune disorders. Tissues that have been removed from patients for medical reasons, such as biopsied tissues, may be examined for tissue and DNA studies. Relatives are studied to determine if some of them may have a very mild form of lymphocyte homeostasis disorder.
Patients who have an immune problem that the researchers wish to study further will be invited to donate additional blood samples at irregular intervals (at least once a year) and to provide an update of their medical records at the same time.
Primary Outcome Measures:
- Objectives: We propose to evaluate patients who may have, or are suspected of having, inherited diseases of lymphocyte homeostasis and programmed cell death. Caspase-8-deficient patients illustrate the dual overlapping roles of certain molecules... [ Time Frame: This study is ongoing. It is not a treatment study, and there are no outcome measures, other than ultimate goals of identifying causative genes, validating genotype phenotype and contributing to the literature, as well as develop potential therapies. ] [ Designated as safety issue: No ]
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This protocol is designed to screen patients with suspected or identified genetic diseases of lymphocyte homeostasis, reflecting abnormalities in programmed cell death, survival, activation, and/or proliferation. Patients determined by clinical history and initial outside evaluation by their referring physician to be of interest will be consented and enrolled into this study. Blood specimens from such patients or their family members will be obtained for research studies related to understanding the genetic and biochemical bases of these diseases. Outside medical records will be obtained for chart review to correlate clinical history to research laboratory testing results. Results will be relayed to the referring physicians and where applicable patients will be referred to other appropriate NIH protocols for additional clinical evaluation and treatment. The study will enroll up to 1000 patients and family members over the next 5 years.