Evaluation of Patients With Immune Function Abnormalities

NCT00128973 | Recruiting

• 2 other identifiers: 05021305-I-0213
• Study Type: observational
• Target: 3,500
• Locations: 1 country
• Sites: 1

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:

• 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

Conditions

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

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

Outcome Measures

Primary Outcomes (4)

• To establish the pattern and pace of change of disease (frequency, distribution, type and extent of infections, inflammatory lesions and abnormalities of immune function) during a period of up to one year baseline assessment.

  Identification pregression and pattern of disease over time

  ongoing throughout study

• To establish the extent of organ involvement (infection and/or inflammation) and organ damage or dysfunction resulting from the abnormality of immune function.

  Identification of severity of disease as it relates to immune function in PID

  ongoing throughout study

• To determine genetic linkage and biochemical correlates of the patient s abnormality of immunity by study of first and second-degree related family members blood cells (buccal smears instead of blood for genetic studies in some individuals)...

  Identification of genetic links and biochemical correlates of PID to clinical manifestations

  ongoing throughout study

• To characterize the physiologic, biochemical or genetic basis of the abnormality of immunity.

  Identification of the pathophysiology and genetic basis of abnormalities of immune function under study

  ongoing throughout study

Secondary Outcomes (3)

• To establish a baseline assessment of the pace and extent of the disease before entering a therapeutic clinical trial.

  ongoing throughout study

• To determine a patient s eligibility for other studies.

  ongoing throughout study

• To assess the patient s ability to safely tolerate specific aspects of other diagnostic or therapeutic research protocols.

  ongoing throughout study

Study Arms (3)

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.

Patients

Patients with abnormalities of immune function

Relatives of Patient:

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

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Self referred, Physician referred

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (5)

• 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.

  PMID: 8462096 BACKGROUND

• 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.

  PMID: 8401490 BACKGROUND

• 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.

  PMID: 8410508 BACKGROUND

• 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.

  PMID: 40178760 DERIVED

• 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.

  PMID: 20489056 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Granulomatous Disease, Chronic; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; Infections; Genetic Diseases, Inborn; Reinfection; X-Linked Combined Immunodeficiency Diseases

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Recurrence; Severe Combined Immunodeficiency; Primary Immunodeficiency Diseases; Infant, Newborn, Diseases

Study Officials

• Harry L Malech, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patricia L Littel, R.N.

CONTACT

(301) 335-1744; plittel@mail.nih.gov

Harry L Malech, M.D.

CONTACT

(301) 480-6916; hmalech@nih.gov

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2005
• First Posted: August 10, 2005
• Study Start: September 19, 2005
• Last Updated: May 1, 2026

Record last verified: 2026-03-31

Locations

US (1)