establishing fibroblast-derived cell lines from skin biopsies of patients with immunodeficiency or immunodysregulation disorders

Conditions: Primary Immunodeficiency; DOCK8; Virus Susceptibility

Summary: background: * national institutes of health (nih) researchers have been studying immune cells (white blood cells) to better understand how the human body s defense system works and adjusts or regulates itself, and how changes in this system can make a person sick. * to study the cells of patients who have problems with their immune systems, researchers would like to collect samples of skin cells from patients with immune system disorders and compare them with skin cells taken from healthy volunteers. by studying these cells, researchers hope to determine whether these cells can be modified to create a new kind of personalized gene therapy that would attempt to cure immune diseases in the future. objectives: * to obtain skin cells from patients with immune system disorders and from healthy volunteers for research and comparison purposes. eligibility: * patients between the ages of 2 and 85 who have immune system disorders. * healthy volunteers between the ages of 18 and 85. * both groups will be selected from the eligible participants of existing nih studies into immune system disorders. design: * researchers may take up to two biopsies from participants arms, legs, abdomen, or back. * the biopsy site will be numbed with local anesthetic and cleaned before the sample is taken. * the punch skin biopsy needle will be inserted into the skin and rotated to remove a small circle of skin (approximately 1/4 to 3/8 of an inch across). the area will be closed with bandages or stitches, and then covered with a dressing. any stitches will be removed in 7 to 10 days. * tissue samples collected in the study will be stored for future research.

this protocol is designed as an adjunct to other national institutes of health (nih) irb approved protocols that allow for genetic testing, which may include those that are screening protocols for patients with rare primary immunodeficiency or immunodysregulation disorders. patients deemed of sufficient research interest after review of outside medical records, clinical evaluation, and testing, may be invited to participate in this study. healthy volunteers and relatives of patients will also be invited to participate as a source of control samples for research testing. after consent and enrollment into this study, skin punch biopsies will be obtained to establish dermal fibroblast cell lines for research studies directed at understanding the genetic and biochemical bases of these diseases. cell lines will also be used to investigate the utility of induced pluripotent stem cells (ips) for lymphocyte derivation and targeted gene correction. the nasal epithelial scrapings will be used for research purposes to grow out primary nasal respiratory epithelial cell lines. these cell lines will be used for functional studies by testing virus replication in them. these functional studies will allow us to identify new primary immunodeficiencies that may present primarily as recurrent or persistent lower respiratory tract virus infections. results with the potential to impact medical care 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 200 patients and healthy volunteers over the next 15 years.

Eligibility criteria:
* inclusion criteria: patients: 1. to be enrolled in this study, a patient must be \>=2 years of age but not \>85 years of age, 2. have a known diagnosis of primary immunodeficiency or immunodysregulation (or be a blood relative of such as patient), 3. be concurrently enrolled on an nih irb approved niaid protocol that includes genetic testing for disease of the immune system, such as but not limited to 05-i-0213 or 06-i-0015 patient relative: to be enrolled in this study, a patient relative must be: 1. a biological relative of a participant being studied under this protocol. relatives may be biological mother, father, sibling, children, grandparents, aunts, uncles and first cousins. a. a minor relative of the proban participant must demonstrate that they are asymptomatic carriers or are at risk for the disease 2. be concurrently enrolled on an nih irb approved protocol that includes genetic testing for disease of the immune system, such as but not limited to 05-i-0213 or 06-i-0015. 3. greater than or equal to 8 years of age but not greater than 85 years of age, healthy volunteers: to be enrolled in this study, a normal volunteer must fulfill all of the following criteria: 1. be enrolled on protocol 05-i-0213. 2. be a healthy adult of either sex and between ages of 18 years and 85 years exclusion criteria: patients or the patient relative are not eligible to be in this trial if:: 1. platelet count less than 20,000/microl 2. the individual is hemodynamically unstable because of acute bleeding. 3. any condition that, in the investigator s opinion, places the patient at undue risk by participating in the study or limits the utility of the specimen to be obtained. 4. for nasal scraping: a history of turbinectomy or significant nasal pathology that would preclude obtaining mucosal scrape biopsies. a healthy volunteer is not eligible to be in this trial if they: 1. areless than 18 years old or older than 85 years 2. weighs less than 110 pounds 3. are pregnant or breastfeeding 4. are receiving a chemotherapeutic agent(s) or has a malignancy 5. cannot avoid taking aspirin or non-steroidal anti-inflammatory medications during the 7 days preceding skin biopsy 6. have history of heart, lung, kidney disease, bleeding disorders, diabetes mellitus, chronic peripheral arterial or venous insufficiency, chronic diffuse skin conditions without uninvolved areas suitable for skin biopsy, poor skin healing, or keloid formation. 7. have been diagnosed as having viral hepatitis (b or c), human immunodeficiency virus (hiv), or a carrier for methicillin-resistant staphylococcus aureus (mrsa) 8. hemoglobin measurement is less than 12.0 g/dl 9. platelet count less than 150,000/(micro)l 10. pt greater than 15.0 seconds or ptt greater than 40 seconds 11. have a history of intravenous injection drug use or of engaging in high-risk activities for exposure to the acquired immunodeficiency syndrome (aids) virus.

Keywords: fibroblast skin biopsy innate immunity induced pluripotent natural history primary immunodeficiency immunodysregulation common variable immunodeficiency severe combined immunodeficiency healthy volunteer hv