Establishing Fibroblast-Derived Cell Lines From Skin Biopsies of Patients With Immunodeficiency or Immunodysregulation Disorders

• ClinicalTrials.gov Identifier: NCT00895271
• Recruitment Status: Enrolling by invitation
• First Posted: May 8, 2009
• Last Update Posted: November 30, 2020
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Study Description

Brief 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.

Condition or disease
Primary Immunodeficiency; DOCK8

Detailed Description:

This protocol is designed as an adjunct to other NIAID 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 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 5 years.

Study Design

• Study Type: Observational
• Actual Enrollment: 97 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Establishing Fibroblast-derived Cell Lines From Skin/Tissue Biopsies of Patients With Immunodeficiency or Immunodysregulation Disorders
• Actual Study Start Date: June 10, 2009

Groups and Cohorts

Group/Cohort
Healthy Volunteers; Up to 50 subjects as healthy controls
Immunodeficiency; Up to 150 subjects with poorly defined, rare inherited immunodeficiency or immunodysregulation disorders

Outcome Measures

Primary Outcome Measures :

1. Generate fibroblast, dermal, or other skin-resident cell lines [ Time Frame: Over the lifetime of the study ]
   Obtain skin punch biopsies to generate fibroblast, dermal, or other skin-resident cell lines in patients who previously underwent HSCT. Cells may also be used for somatic cell hybridization, cell complementation, assessing fibroblast-specific innate immune responses, or other genetic techniques.

Secondary Outcome Measures :

1. Generate induced pluripotent stem cells (iPS) from skin cells [ Time Frame: Over the lifetime of the study ]
   Generate induced pluripotent stem cells (iPS) from skin cells of patients or health volunteers, serving as controls.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 85 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Up to 150 patients with poorly defined, rare inherited immunodeficiency or immunodysregulation disorders, and up to 50 healthy volunteers as controls. Patients and healthy volunteers, who are first evaluated under another NlAlD protocol (such as 05-l-0213 or 06-l-0015) and others, may be offered the opportunity to participate in this protocol.@@@@@@

Criteria

• INCLUSION CRITERIA:

Patients:

To be enrolled in this study, a patient must be >=2 years of age but not >85 years of age, have a known diagnosis of primary immunodeficiency or immunodysregulation (or be a blood relative of such as patient), and 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

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 with a primary immunodeficiency or immunodysregulation disorder (or a blood relative of such a patient) are not eligible to be in this trial if:

• 1. Platelet count less than 20,000/microL
• 2. Patient 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 he or she fulfills any of the following criteria:

• 1. Less than 18 years old or older than 85 years
• 2. Weighs less than 110 pounds
• 3. Is pregnant or breastfeeding
• 4. Is 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. Has 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. Has a history of intravenous injection drug use or of engaging in high-risk activities for exposure to the acquired immunodeficiency syndrome (AIDS) virus.

Contacts and Locations

Locations

United States, Maryland

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Helen C Su, M.D.; National Institute of Allergy and Infectious Diseases (NIAID)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

Su HC, Lenardo MJ. Genetic defects of apoptosis and primary immunodeficiency. Immunol Allergy Clin North Am. 2008 May;28(2):329-51, ix. doi: 10.1016/j.iac.2008.01.002. Review.

Su HC. The technological transformation of patient-driven human immunology research. Immunol Res. 2009;43(1-3):167-71. doi: 10.1007/s12026-008-8062-9.

Schuster SC. Next-generation sequencing transforms today's biology. Nat Methods. 2008 Jan;5(1):16-8. doi: 10.1038/nmeth1156. Epub 2007 Dec 19. Review.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00895271
• Other Study ID Numbers: 090133; 09-I-0133
• First Posted: May 8, 2009
• Last Update Posted: November 30, 2020
• Last Verified: November 6, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):

FIBROBLAST; Skin Biopsy; Primary Immunodeficiency; Immunodysregulation; Common Variable Immunodeficiency; Severe Combined Immunodeficiency; Healthy Volunteer; HV

Additional relevant MeSH terms:

Immunologic Deficiency Syndromes; Immune System Diseases