Study of Autoimmune Lymphoproliferative Syndrome (ALPS)

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/.