Screening Protocol for Genetic Diseases of Lymphocyte Homeostasis and Programmed Cell Death

Screening Protocol for Genetic Diseases of Lymphocyte Homeostasis and Programmed Cell Death

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.

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This protocol is designed to screen patients with suspected or identified genetic diseases of immune cell homeostasis, reflecting abnormalities in programmed cell death, survival, development, 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 and other biological specimens from 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 may be referred to other relevant research studies at the NIH.

The study will enroll up to 5000 patients and family members over the next 20 years.

• INCLUSION CRITERIA:

Patients known to have or suspected of having an inherited immune cell homeostasis, programmed cell death susceptibility syndrome, lymphocyte developmental block, or defective immune cell effector functions will be eligible for enrollment. We will enroll

patients with suspected disease if the investigator agrees that there is a high index of suspicion. Blood relatives of enrolled patients will be eligible for enrollment. There will be no limit as to age, sex, race, or disability.

EXCLUSION CRITERIA:

Severely debilitated health status or poor venous access may preclude obtaining adequate specimens for analysis. The minimum weight for infants on this protocol is 3 kg because of the limits of maximal acceptable blood draw volumes and minimum requirement for core laboratory tests would exceed the acceptable volume.

Co-enrollment guidelines: Participants may be co-enrolled in other studies including NIH protocols 05-I-0213, 93-I-0063 and 17-I-0122. Participants should inform the investigator of participation in other research studies.