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.

In some cases, we may proivide treatment related to ALPS. These treatments are consistent with standard medical practice.

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/.

Condition
Autoimmune Disease Lymphatic Disease Lymphoproliferative Disorder Canale-Smith Syndrome

Further Study Details: 

Expected Total Enrollment:  800

The purpose of the protocol is to allow for patients, and relatives of patients, who may have the newly described Autoimmune Lymphoproliferative Syndrome (ALPS) to be evaluated at the NIH Clinical Center. This evaluation will include blood and relevant tissue studies along with long-term clinical evaluation to define the biology, inheritance, clinical spectrum, and natural history of this syndrome. The aim of the research studies is to elucidate mechanisms underlying heightened polyclonal and autoimmune responses in these patients. Knowledge gained from these studies provides important insights into the mechanisms of autoimmunity, normal thymic and extra thymic T cell differentiation, TCR repertoire selection, and lymphomagenesis. Medically indicated management of ALPS-related autoimmune disease and cytopenias will also be considered and provided, using standard of care treatments.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Study size: up to 800 patients (300 ALPS patients, 500 Relatives and normal controls)
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.
All affected patients who are referred will be considered for enrollment. Clinical histories, laboratory data and pedigrees will be reviewed. Priority will be given to families with informative composition for genetic studies, patients with extensive available documentation of phenotype.
Relatives (any age) of patients and normal controls (18-65)
Recruitment Strategies: Patients and families are referred from NIH investigators, immunologists, hematologists, general medical doctors and geneticists who learn of our studies through our scientific presentations and publications; family organizations, such as the Immune Deficiency Foundation; and the internet.
EXCLUSION CRITERIA:
HIV infection in any potential subject, and recognized or suspected immunologic disorders or complicating medical or psychiatric conditions in potential unrelated controls.

Maryland
      National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  930063; 93-I-0063
Record last reviewed:  December 23, 2003
Last Updated:  March 30, 2005
Record first received:  November 3, 1999
ClinicalTrials.gov Identifier:  NCT00001350
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08