Genetic Studies of Chronic Active Epstein-Barr Disease

NCT00032513 | Recruiting

• 2 other identifiers: 02014702-I-0147
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Active Epstein-Barr Virus

Keywords

Herpes; Hemophagocytosis; Epstein-Barr Virus; Lymphoproliferative Disease; Mononucleosis; Natural History; Epstein-Barr; EBV; CAEBV; Chronic Active Epstein-Barr Virus; Virus

Outcome Measures

Primary Outcomes (1)

• The primary goal of this study is to identify genetic mutations responsible for CAEBV.

  Provide insights into the immunologic control of EBV infections.

  ongoing

Secondary Outcomes (1)

• 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

Study Arms (2)

CAEBV

Patients with chronic active Epstein-Barr virus.

Hydroa vaccineforme

Patients with EBV hydro vaccineforme.

Eligibility Criteria

• Age: 1 Year - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with known or suspected CAEBV and their relatives will be recruited by referrals from health care providers or self-referrals.@@@@@@

You may not qualify if:

• (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.

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 (4)

• Okamura T, Hatsukawa Y, Arai H, Inoue M, Kawa K. Blood stem-cell transplantation for chronic active Epstein-Barr virus with lymphoproliferation. Lancet. 2000 Jul 15;356(9225):223-4. doi: 10.1016/S0140-6736(00)02488-0.

  PMID: 10963205 BACKGROUND

• Cohen JI, Jaffe ES, Dale JK, Pittaluga S, Heslop HE, Rooney CM, Gottschalk S, Bollard CM, Rao VK, Marques A, Burbelo PD, Turk SP, Fulton R, Wayne AS, Little RF, Cairo MS, El-Mallawany NK, Fowler D, Sportes C, Bishop MR, Wilson W, Straus SE. Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood. 2011 Jun 2;117(22):5835-49. doi: 10.1182/blood-2010-11-316745. Epub 2011 Mar 31.

  PMID: 21454450 BACKGROUND

• Cohen JI. Optimal treatment for chronic active Epstein-Barr virus disease. Pediatr Transplant. 2009 Jun;13(4):393-6. doi: 10.1111/j.1399-3046.2008.01095.x. No abstract available.

  PMID: 19032417 BACKGROUND

• Cohen JI, Manoli I, Dowdell K, Krogmann TA, Tamura D, Radecki P, Bu W, Turk SP, Liepshutz K, Hornung RL, Fassihi H, Sarkany RP, Bonnycastle LL, Chines PS, Swift AJ, Myers TG, Levoska MA, DiGiovanna JJ, Collins FS, Kraemer KH, Pittaluga S, Jaffe ES. Hydroa vacciniforme-like lymphoproliferative disorder: an EBV disease with a low risk of systemic illness in whites. Blood. 2019 Jun 27;133(26):2753-2764. doi: 10.1182/blood.2018893750. Epub 2019 May 7.

  PMID: 31064750 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Herpes Simplex; Epstein-Barr Virus Infections; Lymphoproliferative Disorders; Infectious Mononucleosis; Virus Diseases

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Tumor Virus Infections; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukocyte Disorders; Hematologic Diseases

Study Officials

• Jeffrey I Cohen, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeffrey I Cohen, M.D.

CONTACT

(301) 496-5265; jcohen@niaid.nih.gov

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2002
• First Posted: March 25, 2002
• Study Start: April 16, 2002
• Last Updated: May 7, 2026

Record last verified: 2026-04-30

Locations

US (1)