Protocol Number: 02-I-0147

Title:

Genetic Studies of Chronic Active Epstein-Barr Virus Infection

Number:

02-I-0147

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 2 and above) with CAEBV and up to 150 of their relatives (age 2 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.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): None

Eligibility Criteria:

ELIGIBILITY CRITERIA

CAEBV PATIENTS

Study size: up to 50 patients

Sex distribution: male and female

Age range: 2 years and above

Patients known to have CAEBV and their relatives will be recruited by referrals from health care providers. The rarity of this disease will markedly limit the number of patients available to study.

Patient recruitment is irrespective of racial and ethnic group or gender. NIAID investigators will be available to answer questions and discuss general aspects of CAEBV and identified genes or modifier genes with participants or their providers.

Eligibility criteria:

To be considered having CAEBV, a patient must have:

(a) a severe progressive illness that began at least 6 months ago as a primary EBV infection, or associated with markedly elevated EBV-specific antibody titers (IgG-VCA greater than or equal to 1:5,120; EA greater than or equal to 1:640 or EBNA less than 1:2 with other serologies positive) not otherwise explained AND

(b) evidence of major organ involvement such as lymphadenitis, hemophagocytosis, meningoencephalitis, persistent hepatitis, splenomegaly, interstitial pneumonitis, bone marrow hypoplasia, uveitis AND

(c) detection of elevated levels of EBV DNA, RNA or proteins in affected tissues OR elevated levels of EBV DNA in the peripheral blood AND

Exclusion criteria:

(a) no other known immunocompromising condition, including HIV

RELATIVES OF CAEBV PATIENTS

Study size: up to 150 relatives of CAEBV patients

Age range: 2 years and above

To determine the genetic basis for this syndrome, the evaluation of blood and 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 studies on blood 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 EXCLUSIONS:

Known HIV infection in any patient with CAEBV or their relative.

Special Instructions:

Currently Not Provided

Keywords:

Herpesvirus

Hemophagocytosis

Lymphoproliferative

Epstein-Barr

Mononucleosis

Recruitment Keyword(s):

Epstein-Barr

EBV

CAEBV

Chronic Active Epstein-Barr Virus

Virus

Condition(s):

Epstein-Barr Virus Infections

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Allergy and Infectious Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Cohen JI Epstein-Barr virus infection N Engl J Med 2000 Aug 17;343(7):481-92

Schooley RT, Carey RW, Miller G, Henle W, Eastman R, Mark EJ, Kenyon K,Wheeler EO, Rubin RH Chronic Epstein-Barr virus infection associated with fever and interstitialpneumonitis Clinical and serologic features and response to antiviral chemotherapyAnn In

Straus SE The chronic mononucleosis syndrome J Infect Dis 1988 Mar;157(3):405-12

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

National Institutes of Health Clinical Center Bethesda, Maryland 20892. Last update: 01/30/2009