Protocol Number: 93-I-0063

Title:

Study of the Immunopathogenesis, Natural History, and Genetics of Autoimmune Lymphoproliferative Syndrome (ALPS) Associated with an Expansion of CD4-8-/TCR alpha/beta+ T Cells and Defective Lymphocyte Apoptosis

Number:

93-I-0063

Summary:

The purpose of the protocol is to allow for patients, and relatives of patients, who may have the newly described autoimmune lymphoproliferative syndrome, to be evaluated at the NIH Clinical Center. This evaluation will include blood and relevant tissue studies along with long-term clinical evaluations to define the biology, inheritance,clinical spectrum, and natural history of this syndrome. The aim of the research is to understand mechanisms involved in the development of expanded numbers of what is typically a rare population of immune cells (CD4-8-/TCRalpha/beta+ T cells, otherwise referred to as double negative T cells), and how these relate to the development of expanded numbers of immune cells and autoimmune (self against self) responses in patients with ALPS.

Participants with ALPS will be invited to visit the NIH once a year or more frequently when clinically indicated for the next few years for clinicians and scientists to follow the course of their disease and to manage its complications. Knowledge gained from these studies provides important insights into the mechanisms of autoimmunity, the thymus gland, and the role that the immune system and genetics plays in ALPS.

Autoimmune lymphoproliferative syndrome is a rare disease that affects both children and adults. Each of these three words helps describe the main features of this condition. The word autoimmune (self-immune) identifies ALPS as a disease of the immune system. The tools used to fight germs turn against our own cells and cause problems. The word lymphoproliferative describes the unusually large numbers of white blood cells (called lymphocytes (stored in the lymph nodes and spleens of people with ALPS. The word syndrome refers to the many common symptoms shared by ALPS patients.

One of the causes of ALPS is defective apoptosis, or said another way, an individual has an abnormality in how well lymphocytes (immune cells) die when they are instructed to do so. It is normal for lymphocytes to disintegrate (e.g., die) when they have done their job. In people with ALPS and in some of their affected relatives, the genetic message for the cells to die is altered: the message is not received and the cells do not die when they should. As a result, people with ALPS develop an enlarged spleen, liver and lymph glands, along with a range of other problems involving white blood cell counts and overactive immune responses (autoimmune disease). Some patients have an increased risk of developing lymphatic cancers (lymphoma).

Provided is a description of eligible study candidates:

1.) Any patient with ALPS, male or female and of any age. As a patient with ALPS, candidates must have:

- a medical history of an enlarged spleen and/or enlarged lymph nodes over an extended period of time (past and/or current).

- defective lymphocyte apoptosis, in vitro.

- greater than or equal to 1 percent TCR alpha/beta+CD4-8- peripheral blood T cells.

2.) Relatives (any age) of patients and normal controls (18-65).

3.) Healthy normal volunteers will also be enrolled to provide data on normal cell behavior for comparison with patients.

Additional information regarding ALPS and the research being conducted at the National Institutes of Health is available at the following World Wide Web (e.g., Internet) locations:

http://www.niaid.nih.gov/publications/alps/

http://www.nhgri.nih.gov/DIR/GMBB/ALPS/.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Study size: up to 300 patients

Sex Distribution: Male and female

Age range: All ages acceptable

To be considered as having ALPS, patients must have greater than or equal to 1 percent TCR alpha/beta+ CD4-8- peripheral blood T cells, along with: A history of chronic splenomegaly and/or lymphadenopathy; Defective lymphocyte apoptosis, in vitro.

Relatives (any age) of patients and normal controls (18-65)

EXCLUSION CRITERIA:

HIV infection in any potential subject, and recognized or suspected immunologic disorders or complicating medical or psychiatric conditions in potential unrelated controls.

Special Instructions:

This protocol studies the long term effects of your disease. Therefore, you will be invited to visit the NIH once a year or more frequently for the next few years so that we can follow the progression of your disease and manage its complications.

Keywords:

Immunoregulation

T Cell Receptor Alpha/Beta

Lymphadenopathy

Recruitment Keywords:

Autoimmune Lymphoproliferative Syndrome

ALPS

Conditions:

Autoimmune Disease

Lymphatic Disease

Lymphoproliferative Disorder

Canale-Smith Syndrome

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

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

Citations:

A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease

Dominant interfering gas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome

Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity

• 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 Networks and Applications, CC.

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