Apheresis and CD34+ Selection of Mobilized Peripheral Blood CD34+ Cells From Patients With DOCK8 Deficiency, LAD-1, and GATA2 Deficiency
Background: \- Gene therapy is being investigated as a possible treatment for individuals with immunodeficiency diseases or other conditions that make it difficult to fight off infection. Gene therapy avoids problems with donor identification and possible rejection of bone marrow transplant by using the patient s own modified blood cells to help treat the disease. Researchers are interested in collecting stem cells from the blood of individuals with immunodeficiency diseases in order to use the cells to develop potential gene therapy treatments.
Objectives: \- To collect blood stem cells from patients with immunodeficiency diseases tto test our ability to correct the defects of these cells in the test tube.
Eligibility: * Individuals between 18 and 40 years of age with immunodeficiency diseases. * Individuals with human immunodeficiency virus (HIV) will not be able to participate in this study.
Design: * Participants will provide an initial blood sample for disease screening (such as hepatitis B and C, syphilis, or viruses like the Epstein-Barr virus, herpes simplex virus, or toxoplasmosis) and to check kidney and liver function. * Starting 5 days before blood donation, participants will receive daily injections of a drug called G-CSF (granulocyte colony stimulating factor, or filgrastim), which pushes stem cells out of the bone marrow and into the bloodstream. Participants will receive the injections at the National Institutes of Health Clinical Center. * On day 5, participants will have a single leukapheresis procedure to collect the stem cells from the blood. * No additional treatment will be provided as part of this protocol. The cells that are collected will be used fore experiments in the lab and will not be used to treat individuals with these diseases.
• Individuals age 18-40 years.
• Diagnosis of DOCK8 deficiency, LAD-1, or GATA2 Deficiency:
⁃ DOCK8 deficiency
⁃ Homozygous or compound heterozygous mutations in the DOCK8 gene.
‣ LAD-1
⁃ Less than 10% CD18 expression on the neutrophil surface.
‣ GATA2 Deficiency
⁃ Deleterious mutation of GATA2 Gene
• Serum creatinine \<1.5 mg/dL.
• Total Bilirubin \< 3mg/dl, ALT and AST \< 5X upper limit of normal.
• Ability to give informed consent.
• Adequate venous access for peripheral apheresis, or consent to use a temporary central venous catheter for apheresis.
• Individuals of childbearing age must have a negative urine pregnancy test within one week prior to beginning filgrastim or filgrastim biosimilar administration.