Genetic Studies of Chronic Active Epstein-Barr Disease
- Conditions
- Chronic Active Epstein-Barr Virus
- Registration Number
- NCT00032513
- Brief Summary
Epstein-Barr virus (EBV) is a member of the human herpes virus family that infects more than 95 percent of the U.S. population. Most infections occur in childhood and cause no symptoms; in adolescents and adults, EBV often causes infectious mononucleosis. It has also been associated with certain forms of cancer. Chronic Epstein-Barr virus (CAEBV) is a rare disease, primarily of children and young adults, that leads to life-threatening infections.
This study seeks to identify genetic mutations responsible for CAEBV. A secondary goal is to learn more about the natural history of CAEBV.
The study will examine blood and tissue samples from up to 50 patients (age 3 and above) with CAEBV and up to 150 of their relatives (age 1 and above). Autopsy samples may be included in the study. Up to 300 anonymous blood samples from the NIH Clinical Center Blood Transfusion Medicine will also be examined for comparison.
No more than 450 milligrams (30 tablespoons) of blood per 8 weeks will be drawn from adult patients, and no more than 7 milliliters per kilogram of blood per 8 weeks will be drawn from patients under age 18. Local health care providers will refer patients to the study and will obtain the samples. Some patients may also be seen at the NIH Clinical Center. Those patients will have a full medical history and physical examination, along with chest X-ray, blood counts, blood chemistry, EBV serologies, and viral load. Other tests, such as CT scan or MRI, may be performed if medically indicated. Patients will be asked to undergo leukapheresis.
In vitro tests on the blood or tissue samples will include analysis for proteins or genes that are involved in the immune response; cloning of portions of patient DNA; transformation of B cells with EBV; measurement of the ability of patient blood cells to kill EBV-infected cells; determination of lymphocyte subsets; and determination of antibodies to EBV or other herpes viruses.
If a genetic cause for CAEBV is found, the investigators will be available to discuss the results with patients in person or by telephone. Genetic indications of risk for other diseases will also be discussed with patients.
- Detailed Description
Patients with chronic active Epstein-Barr virus (CAEBV) have (a) an illness that began as a primary infection with EBV or markedly elevated titers of antibodies to EBV, (b) histological evidence of organ disease, and (c) elevated EBV DNA levels in the blood or EBV DNA or proteins in affected tissues. This is primarily a disease of children and young adults. Many of these patients develop hypogammaglobulinemia or pancytopenia and death is frequently due to opportunistic infections or T cell lymphoproliferative disease. The primary goal of this study is to identify genetic mutations responsible for CAEBV. The secondary goal of this study is to learn more about the natural history of CAEBV. Blood samples or available tissues (e.g., previous biopsy or autopsy material) from patients with CAEBV and their relatives will be analyzed to identify disease genes that are mutated in this population. In addition, some of the patients will be invited to come for evaluation at the NIH Clinical Center. At that time, medically indicated studies of disease progression will be performed. Serial virologic and immunologic studies will be performed. Eligible relatives of patients will be studied to compare the gene(s) associated with CAEBV in patients with the gene(s) in their relatives. Knowledge gained from this study has the potential of providing insights into the immunologic control of EBV infections. In addition, identification of the molecular mechanisms for CAEBV may provide insights leading to improved treatments for this disease.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
Not provided
(a) Any other condition that, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in the study.
RELATIVES OF CAEBV PATIENTS:
Study size: up to 150 relatives of CAEBV patients
Age range: 3 years and above
To determine the genetic basis for this syndrome, the evaluation of blood, saliva and/or previously obtained tissue specimens from healthy relatives of CAEBV patients will serve as controls. No tissue biopsies will be performed on healthy relatives. We will
perform some of the studies listed on samples from normal relatives.
UNRELATED VOLUNTEERS
Study size: up to 300 persons
Age range: 18 years and above
Panels of anonymous blood samples will be obtained through NIH Clinical Center Blood Transfusion Medicine to determine if identified genetic changes are mutations or polymorphisms.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary goal of this study is to identify genetic mutations responsible for CAEBV. ongoing Provide insights into the immunologic control of EBV infections.
- Secondary Outcome Measures
Name Time Method The secondary goal of this study is to learn more about the natural history of CAEBV, to assess the viral burden and localization, and to determine if defects are present in pathways involved in cytotoxic functions of T or NK cells. ongoing Identification of the molecular mechanisms fro CAEBV.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States