Evaluation of Patients With Immune Function Abnormalities

NCT ID: NCT00128973

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 3500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2005-09-19

Brief Summary

This study will evaluate patients with abnormal immune function that results in recurrent or unusual infections or chronic inflammation. This may include inherited conditions, such as X-linked severe combined immunodeficiency (XSCID), chronic granulomatous disease (CGD), and leukocyte adhesion deficiency (LAD), or conditions resulting from outside factors, such as graft-versus-host disease (GVHD). The information from this study will be used to establish the pattern and pace of change of the disease and to help develop new treatments. The period of observation and study following enrollment in this study may be for up to one year. In addition these studies may provide the medical information needed to determine eligibility for enrollment in other clinical study protocols and more prolonged follow up.

Patients of any age with abnormal immune function who have recurrent or unusual infections, whose blood tests show evidence of immune dysfunction, or who have GVHD, XSCID, CGD or LAD may be eligible for this study. Patients' parents, siblings, grandparents, children, aunts, uncles and first cousins of any age also may be included. Healthy normal volunteers between 18 and 85 years of age are recruited as controls.

Normal volunteers undergo a physical examination and provide blood, saliva, and urine samples for immune function studies. Patients' family members provide a medical history, have a physical examination, and give blood and urine samples, and possibly a saliva sample. The samples are used for genetic and routine laboratory studies. Investigators may request tissue samples, such as biopsy specimens, previously removed for medical reasons to be sent to NIH for study. Patients undergo the following tests and procedures:

1. Medical history and physical examination.

2. Blood and urine tests, including analysis for genes involved in immune disorders.

3. Buccal smear (in some patients) for genetic studies. This involves scraping the lining of the mouth near the cheek.

4. Specialized tests to evaluate specific conditions in patients who have an immune disorder that might affect lung function, gum infections or eye problems. These may include chest x-ray, CT scan, breathing function test, dental, eye, and hearing examinations.

5. Follow-up visits of patients with immune problems may occur at 6 months and at one year after the first visit (or more frequently if medically required) to include:

• Medical history update
• Physical examination
• Follow-up on abnormal test results and medical treatments initiated at NIH
• Collection of blood, saliva, urine, or wound drainage samples for repeat immune function studies
• Tissue study of specimens removed for medical reasons at other institutions besides NIH

Detailed Description

This protocol is designed for the screening and baseline assessment of and collection of research samples from patients with abnormalities of immune function as manifested by recurrent or unusual infections, recurrent or chronic inflammation, or previous laboratory evidence of immune dysfunction. After baseline assessments are complete, participants will remain on study to allow long-term assessments of the natural course of their condition. Abnormalities of immune function may be inherited or may be iatrogenic such as that following hematopoietic stem cell transplantation or other treatments resulting in prolonged immune dysfunction. Blood and/or bone marrow cells may also be used to investigate the utility of induced pluripotent stem cells (iPS) for immune cell derivation and targeted gene correction. This is not a protocol to study or screen for human immunodeficiency virus (HIV) infection, though patients with HIV infection who may have other causes for immune dysfunction are not excluded. First- or second-degree genetically related family members (limited to mother, father, siblings, grandparents, children, aunts, uncles, and first cousins of an affected patient) may also be screened for clinical, in vitro, and genetic correlates of immune abnormalities. Healthy Volunteers will be enrolled as a source of control blood samples for research testing, not to include genetic testing. Patients with documented immune dysfunction may receive limited medically indicated treatment if that medically indicated treatment is related to the abnormality of immune function under study. Results of clinically indicated diagnostic evaluations and treatments performed outside of this protocol may be collected for research use as part of this study. When screening and assessment is complete, patients will be offered an opportunity to participate in another study, or if there are no active studies appropriate for the patient, other options will be suggested to the primary or referring physician. Regardless of whether the patient enrolls on another NIH study, they will remain on this study for long-term follow-up of their condition.

This protocol will allow detailed long-term investigation of patients with abnormalities of immune function with the following goals:

1. To determine the degree, scope, and cause of immune dysfunction;

2. To establish the pace and pattern of change in the disease process;

3. To determine the extent of organ involvement and damage from immune dysfunction.

The assessments performed under this protocol are necessary to discover new causes of immune abnormalities, to delineate epidemiology of immune deficiencies, to develop new diagnostic and therapeutic tools, and to determine a patient s eligibility for other studies.

Conditions

Chronic Granulomatous Disease (CGD); X-Linked Severe Combined Immune Deficiency (XSCID); Leukocyte Adhesion Deficiency 1 (LAD); Graft Versus Host Disease (cGvHD)

Keywords

Infection; Genetic; Inherited Disease; Immunity; Chronic; Abnormal Immune Function; Recurrent Infection; Chronic Granulomatous Disease; CGD; X-Linked Severe Combined Immune Deficiency (XSCID); XSCID; Leukocyte Adhesion Deficiency 1; LAD; Healthy Volunteer; HV

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Healthy Volunteers

Healthy adult M/F 18-85 y/o.Hgb\>=11.Wt\>110 lbs. No heart,lung,kidney,bleeding disorders. No hep BorC since age 11. No IV drug use. No exposure to the AIDS virus. Not pregnant.

No interventions assigned to this group

Patients

Patients with abnormalities of immune function

No interventions assigned to this group

Relatives of Patient:

Relatives may be mother, father, siblings, children, grandparents, aunts, uncles, and first cousins to a patient.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

Patients:

To be eligible to participate in this study as a patient, an individual must meet the following criteria:

• Must be 2 years of age to be seen at the Clinical Center as an outpatient and they must not have any active infections. Send-in samples for clinical diagnosis at any age.
• Have an abnormality of immune function as manifested by:

• recurrent or unusual infections,
• recurrent or chronic inflammation, or
• previous laboratory evidence of immune dysfunction.
• Have a primary physician outside of the NIH.

Relatives of Patient:

To be eligible to participate in this study as a patient relative, an individual must meet the following criteria:

• Be a biological mother, father, sibling, child, grandparent, aunt, uncle, or first cousin to a patient.

--Sibling, child, first cousin, aunt, and uncle must be 2 years of age to be seen at the Clinical Center as an outpatient with no active infections, Send-in samples for clinical diagnosis at any age.

• Be willing to have blood stored for future studies and/or other research purposes.

Healthy Volunteers:

To be eligible to participate in this study as a healthy volunteer, an individual must meet the following criteria:

• Be a healthy adult of either sex and between age of 18 and 85 years old.
• Have a hemoglobin count of >=11.
• Weight greater than 110 pounds.
• Not have a history of intravenous injection drug use.
• Not have a history of engaging in high-risk activities for exposure to HIV.
• Be willing to have their blood samples stored for future research and modified to iPS cells.

Exclusion Criteria

Patients and Relatives of Patient:

Healthy Volunteers:

An individual who meets any of the following criteria will be excluded from participation as a healthy volunteer in this study:

• Have HIV or viral hepatitis (B or C), or history of viral hepatitis B or C since age 11.
• Receiving chemotherapeutic agent(s) or have underlying malignancy.
• Pregnant.
• Have history of heart, lung, kidney disease, or bleeding disorders.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Harry L Malech, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Allergy and Infectious Diseases (NIAID)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Patricia L Littel, R.N.

Role: CONTACT

Phone: (301) 335-1744

Email: plittel@mail.nih.gov

Harry L Malech, M.D.

Role: CONTACT

Phone: (301) 480-6916

Email: hmalech@nih.gov

Facility Contacts

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Role: primary

References

Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW, Leonard WJ. Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell. 1993 Apr 9;73(1):147-57. doi: 10.1016/0092-8674(93)90167-o.

Reference Type: BACKGROUND

PMID: 8462096 (View on PubMed)

Puck JM, Deschenes SM, Porter JC, Dutra AS, Brown CJ, Willard HF, Henthorn PS. The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1. Hum Mol Genet. 1993 Aug;2(8):1099-104. doi: 10.1093/hmg/2.8.1099.

Reference Type: BACKGROUND

PMID: 8401490 (View on PubMed)

Stephan JL, Vlekova V, Le Deist F, Blanche S, Donadieu J, De Saint-Basile G, Durandy A, Griscelli C, Fischer A. Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients. J Pediatr. 1993 Oct;123(4):564-72. doi: 10.1016/s0022-3476(05)80951-5.

Reference Type: BACKGROUND

PMID: 8410508 (View on PubMed)

Strong J, Adhanom R, Kim CS, Saito Y, Meltzer JC, Hallaert P, Martinez S, Salancy A, Kong HH, Cowen EW, Castelo-Soccio L, Murphy PM, McDermott DH, Brownell I. Risk of Superficial Fungal Infections in WHIM Syndrome. Dermatol Ther (Heidelb). 2025 May;15(5):1173-1179. doi: 10.1007/s13555-025-01396-0. Epub 2025 Apr 3.

Reference Type: DERIVED

PMID: 40178760 (View on PubMed)

De Ravin SS, Cowen EW, Zarember KA, Whiting-Theobald NL, Kuhns DB, Sandler NG, Douek DC, Pittaluga S, Poliani PL, Lee YN, Notarangelo LD, Wang L, Alt FW, Kang EM, Milner JD, Niemela JE, Fontana-Penn M, Sinal SH, Malech HL. Hypomorphic Rag mutations can cause destructive midline granulomatous disease. Blood. 2010 Aug 26;116(8):1263-71. doi: 10.1182/blood-2010-02-267583. Epub 2010 May 20.

Reference Type: DERIVED

PMID: 20489056 (View on PubMed)

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2005-I-0213.html

NIH Clinical Center Detailed Web Page

Other Identifiers

05-I-0213

Identifier Type: -

Identifier Source: secondary_id

050213

Identifier Type: -

Identifier Source: org_study_id