This protocol is designed to study the techniques needed to develop gene therapy or other treatments for certain inherited immune system diseases.
Healthy normal volunteers between 18 and 65 years of age and patients with chronic granulomatous disease (CGD), X-linked severe combined immune deficiency (X-SCID), leukocyte adhesion deficiency (LAD), interferon gamma receptor deficiency (IGR-deficiency) or other inherited diseases affecting precursor blood cells bone marrow cells that generate blood cells may be eligible for this study. Patients who have had repeated severe infections possibly due to an inherited blood cell abnormality may also participate. Candidates will be screened with a medical history, physical examination and blood tests.
Patients with an active infection will be hospitalized during this study. Uninfected participants will be seen as outpatients at the NIH Clinical Center. Participants will have the following procedures:
- G-CSF administration All participants will have daily injections of granulocyte-colony stimulating factor (G-CSF). This drug is a genetically engineered hormone that stimulates the bone marrow to release white blood cells and white cell precursors into the bloodstream. The injections are given under the skin in the arm or leg, using a very small needle. Patients will have injections for 6 or 7 days, normal volunteers for 5. A small blood sample will be drawn each day of the injections to monitor white cell counts and changes in the number of blood cell precursors. (Smaller children and all children under 10 years of age may have blood drawn on alternate days or less to reduce the number of needle sticks and the amount of blood taken.). Larger blood draws will be taken on days 6 and/or 7 for patients and on days 5 and/or 6 for normal volunteers.
- Leukapheresis This procedure for collecting larger numbers of circulating blood precursor cells is optional and may take the place of the larger blood draw described above. Patients 5 years old or older may have leukapheresis. Whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The desired cells are then removed and the rest of the blood is returned to the body, either through the same needle or through a second one placed in the other arm. The cells obtained will be used to purify blood precursors for growing in culture and to examine the ability to transfer new genes into these precursor cells. For patients whose arm veins are too scarred to for needle placement, a vein in the groin area (femoral vein) may be used instead.
- Bone marrow aspiration This procedure for obtaining a bone marrow sample is optional. Normal volunteers who agree to the procedure may undergo aspiration up to three times. The hip area is anesthetized and a small sample of bone marrow is drawn through a special needle inserted in the hipbone. The first aspiration is done on a day before the G-CSF injections are started; the second is done soon after the last injection (day 6 or 7), and the third is done from 7 to 10 days after the last injection.
- Repeat blood tests At day 6 or 7 some of the blood tests done at the beginning of the study will be repeated to check blood counts and liver and kidney function.
Four months or more after the end of the study, participants will be asked to repeat the entire procedure to examine the effects of two cycles of G-CSF mobilization in the same individual. This second cycle is optional.